This is yet another article about the COVID-19 Virus. While I have several articles already on the virus, I am finding that some of my articles are becoming too unwieldy as I continue to update the as new information becomes available. So as more and more variants appear I have decided to write an article just discussing the variants. I will continue to update my two part flagship covid posting and my vaccine posting as well.
Table of Contents
–SARS-CoV-2 Variant Classifications and Definitions
–What’s the concern about the new COVID-19 variants? Are they more contagious?
–COVID Variants: What You Should Know
–WHO labels new Covid strain, named omicron, a ‘variant of concern,’ citing possible increased reinfection risk
–What are the Covid variants and will vaccines still work?
–There’s Always Going To Be Another Variant
–Why you shouldn’t panic over the Omicron variant
-How bad is Omicron? What scientists know so far
-Beyond Omicron: what’s next for COVID’s viral evolution
–Most Who Took COVID Vax will be dead by the year 2025.
-COVID-19 variants will keep coming until everyone can access vaccines
-Omicron’s feeble attack on the lungs could make it less dangerous
-The Omicron Variant: Mother Nature’s COVID-19 Vaccine?
-Is Omicron really less severe than Delta? Here’s what the science says.
-Omicron thwarts some of the world’s most-used COVID vaccines
-Deltacron: the story of the variant that wasn’t
-Where did Omicron come from? Three key theories
-Will Omicron end the pandemic? Here’s what experts say
-COVID reinfections surge during Omicron onslaught
-The 3 main theories for Omicron’s origins
-Why does the Omicron sub-variant spread faster than the original?
-Are COVID surges becoming more predictable? New Omicron variants offer a hint
-Two new Omicron variants are spreading. Will they drive a new U.S. surge?
-Why call it BA.2.12.1? A guide to the tangled Omicron family
-How months-long COVID infections could seed dangerous new variants
-Why Omicron variants BA.4 and BA.5 are causing fresh U.S. outbreaks
-Omicron BA.4.6 is slowly rising and Evusheld won’t work, FDA warns
-What comes after Omicron? New variants are emerging.
-Surprising Omicron origins study comes under scrutiny
-Coronavirus in the U.S.: Where cases are growing and declining
SARS-CoV-2 Variant Classifications and Definitions
Viruses like SARS-CoV-2 continuously evolve as changes in the genetic code (genetic mutations) occur during replication of the genome. A lineage is a genetically closely related group of virus variants derived from a common ancestor. A variant has one or more mutations that differentiate it from other variants of the SARS-CoV-2 viruses. As expected, multiple variants of SARS-CoV-2 have been documented in the United States and globally throughout this pandemic. To inform local outbreak investigations and understand national trends, scientists compare genetic differences between viruses to identify variants and how they are related to each other.
- Mutation: A mutation refers to a single change in a virus’s genome (genetic code). Mutations happen frequently, but only sometimes change the characteristics of the virus.
- Lineage: A lineage is a group of closely related viruses with a common ancestor. SARS-CoV-2 has many lineages; all cause COVID-19.
- Variant: A variant is a viral genome (genetic code) that may contain one or more mutations. In some cases, a group of variants with similar genetic changes, such as a lineage or group of lineages, may be designated by public health organizations as a Variant of Concern or a Variant of Interest due to shared attributes and characteristics that may require public health action.
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- Genetic lineages of SARS-CoV-2 have been emerging and circulating around the world since the beginning of the COVID-19 pandemic.
- SARS-CoV-2 genetic lineages in the United States are routinely monitored through epidemiological investigations, virus genetic sequence-based surveillance, and laboratory studies.
- On November 30, 2021, the U.S. government SARS-CoV-2 Interagency Group (SIG) classified Omicron as a Variant of Concern (VOC). This classification was based on the following:
- Detection of cases attributed to Omicron in multiple countries, including among those without travel history.
- Transmission and replacement of the Delta variant in South Africa.
- The number and locations of substitutions in the spike protein.
- Available data for other variants with fewer substitutions in the spike protein that indicate a reduction in neutralization by sera from vaccinated or convalescent individuals.
- Available data for other variants with fewer substitutions in the spike protein that indicate reduced susceptibility to certain monoclonal antibody treatments.
- The SIG Variant classification scheme defines four classes of SARS-CoV-2 variants:
- Variant Being Monitored (VBM)
- Alpha (B.1.1.7 and Q lineages)
- Beta (B.1.351 and descendent lineages)
- Gamma (P.1 and descendent lineages)
- Epsilon (B.1.427 and B.1.429)
- Eta (B.1.525)
- Iota (B.1.526)
- Kappa (B.1.617.1)
- Mu (B.1.621, B.1.621.1)
- Zeta (P.2)
- Variant of Interest (VOI)
- Variant of Concern (VOC)
- Delta (B.1.617.2 and AY lineages)
- Omicron (B.1.1.529)
- Variant of High Consequence (VOHC)
- Variant Being Monitored (VBM)
- To date, no variants of high consequence have been identified in the United States.
- Vaccines approved and authorized for use in the United States are effective against the predominant variant circulating in the United States and effective therapeutics are available. CDC continues to monitor all variants circulating within the United States.
How Variants Are Classified
The U.S. Department of Health and Human Services (HHS) established a SARS-CoV-2 Interagency Group (SIG) to enhance coordination among CDC, National Institutes of Health (NIH), Food and Drug Administration (FDA), Biomedical Advanced Research and Development Authority (BARDA), and Department of Defense (DoD). This interagency group is focused on the rapid characterization of emerging variants and actively monitors their potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics.
The SIG meets regularly to evaluate the risk posed by SARS-CoV-2 variants circulating in the United States and to make recommendations about the classification of variants. This evaluation is undertaken by a group of subject matter experts who assess available data, including variant proportions at the national and regional levels and the potential or known impact of the constellation of mutations on the effectiveness of medical countermeasures, severity of disease, and ability to spread from person to person. Given the continuous evolution of SARS-CoV-2 and our understanding of the impact of variants on public health, variants may be reclassified based on their attributes and prevalence in the United States.
- Variants being monitored (VBM)– View current VBM in the United States that continue to be monitored and characterized by federal agencies
- Variant of interest (VOI)– Currently, no SARS-CoV-2 variants are designated as VOI
- Variant of Concern (VOC)– View current VOC in the United States that are being closely monitored and characterized by federal agencies
- Variant of high consequence (VOHC)– Currently, no SARS-CoV-2 variants are designated as VOHC
Notes: Each variant classification includes the possible attributes of lower classes (for example, VOC includes the possible attributes of VOI); variant status might escalate or deescalate based on emerging scientific evidence. This page will be updated as needed to show the variants that belong to each class. The World Health Organization (WHO) external icon also classifies variant viruses as variants of concern and variants of interest; U.S. classifications may differ from those of WHO because the impact of variants may differ by location. To assist with public discussions of variants, WHO proposed using labels consisting of the Greek alphabet (for example, alpha, beta, gamma) as a practical way to discuss variants for non-scientific audiences. The labels assigned to each variant are provided in the tables below.
CDC monitors all variants circulating in the United States. Variants designated as VBM include those where data indicates there is a potential or clear impact on approved or authorized medical countermeasures or that have been associated with more severe disease or increased transmission but are no longer detected, or are circulating at very low levels, in the United States. These variants do not pose a significant and imminent risk to public health in the United States.
A Variant of Interest or a Variant of Concern may be downgraded to this list after a significant and sustained reduction in its national and regional proportions over time, or other evidence indicates that a variant does not pose significant risk to public health in the United States.
These variants continue to be closely monitored to identify changes in their proportions and new data are continually being analyzed. If the data indicate that a VBM warrants more concern, the classification will be changed based on the SIG assessment of the attributes of the variant and the risk to public health in the United States.
Variant of Interest (VOI)
A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.
Possible attributes of a Variant of Interest:
- Specific genetic markers that are predicted to affect transmission, diagnostics, therapeutics, or immune escape.
- Evidence that it is the cause of an increased proportion of cases or unique outbreak clusters.
- Limited prevalence or expansion in the US or in other countries.
A Variant of Interest might require one or more appropriate public health actions, including enhanced sequence surveillance, enhanced laboratory characterization, or epidemiological investigations to assess how easily the virus spreads to others, the severity of disease, the efficacy of therapeutics and whether currently approved or authorized vaccines offer protection.
Currently, no SARS-CoV-2 variants are designated as VOI.
A variant for which there is evidence of an increase in transmissibility, more severe disease (for example, increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
Possible attributes of a variant of concern:
In addition to the possible attributes of a variant of interest
- Evidence of impact on diagnostics, treatments, or vaccines
- Widespread interference with diagnostic test targets
- Evidence of substantially decreased susceptibility to one or more class of therapies
- Evidence of significantly decreased neutralization by antibodies generated during previous infection or vaccination
- Evidence of reduced vaccine-induced protection from severe disease
- Evidence of increased transmissibility
- Evidence of increased disease severity
Variants of concern might require one or more appropriate public health actions, such as notification to WHO under the International Health Regulations, reporting to CDC, local or regional efforts to control spread, increased testing, or research to determine the effectiveness of vaccines and treatments against the variant. Based on the characteristics of the variant, additional considerations may include the development of new diagnostics or the modification of vaccines or treatments.
Current variants of concern in the United States that are being closely monitored and characterized are listed below. This table will be updated when a new variant of concern is identified.Footnotes for Variants of Concern
Characteristics of Selected SARS-CoV-2 Variants
WHO Label: Delta
Pango Lineage: B.1.617.2 and AY lineages (Pango lineageexternal icon)a
Spike Protein Substitutions: T19R, (V70F*), T95I, G142D, E156-, F157-, R158G, (A222V*), (W258L*), (K417N*), L452R, T478K, D614G, P681R, D950N
Nextstrain clade (Nextstrainexternal icon)b: 21A/S:478K
First Identified: India
- Increased transmissibility29
- Nearly all lineages designated as Delta are susceptible to Emergency Use Authorization (EUA) monoclonal antibody treatments. AY.1 and AY.2 lineages are not susceptible to some monoclonal antibody treatments.7, 14
- Reduction in neutralization by post-vaccination sera21
WHO Label: Omicron
Pango Lineage: B.1.1.529 (Pango lineageexternal icon)a
Spike Protein Substitutions: A67V, del69-70, T95I, del142-144, Y145D, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F
Nextstrain clade (Nextstrainexternal icon)b: 21K
First Identified: South Africa
- Potential increased transmissibility
- Potential reduction in neutralization by some EUA monoclonal antibody treatments
- Potential reduction in neutralization by post-vaccination sera
A VOHC has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.
Possible attributes of a variant of high consequence:
In addition to the possible attributes of a variant of concern
- Impact on MCMs
- Demonstrated failure of diagnostic test targets
- Evidence to suggest a significant reduction in vaccine effectiveness, a disproportionately high number of infections in vaccinated persons, or very low vaccine-induced protection against severe disease
- Significantly reduced susceptibility to multiple EUA or approved therapeutics
- More severe clinical disease and increased hospitalizations
A variant of high consequence would require notification to WHO under the International Health Regulations, reporting to CDC, an announcement of strategies to prevent or contain transmission, and recommendations to update treatments and vaccines.
Currently, no SARS-CoV-2 variants are designated as VOHC.
What’s the concern about the new COVID-19 variants? Are they more contagious?
Viruses constantly change through mutation. When a virus has one or more new mutations it’s called a variant of the original virus. Currently, one variant of the virus (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) is creating concern in the U.S.
- Delta (B.1.617.2). This variant is now the most common COVID-19 variant in the U.S. It’s nearly twice as contagious as earlier variants and might cause more severe illness. The greatest risk of transmission is among unvaccinated people. People with vaccine breakthrough infections also may spread COVID-19 to others. However, it appears that vaccinated people spread COVID-19 for a shorter period than do unvaccinated people. This variant also might reduce the effectiveness of some monoclonal antibody treatments and the antibodies generated by a COVID-19 vaccine.
In addition, the World Health Organization has classified the new variant omicron as a variant of concern. Omicron has been found in several countries. However, it’s not yet clear if omicron spreads more easily or causes more severe disease than other variants, such as delta. Research is underway.
The alpha, gamma and beta variants continue to be monitored but are spreading at much lower levels in the U.S. The mu variant is also being monitored.
While research suggests that COVID-19 vaccines are slightly less effective against the variants, the vaccines still appear to provide protection against severe COVID-19. For example:
- Early research from the U.K. suggests that, after full vaccination, the Pfizer-BioNTech COVID-19 vaccine is 88% effective at preventing symptomatic COVID-19 virus caused by the delta variant. The vaccine is 96% effective at preventing severe disease with the COVID-19 virus caused by the delta variant. The research also showed that the vaccine is 93% effective at preventing symptomatic COVID-19 virus caused by the alpha variant.
- Early research from Canada suggests that, after one dose, the Moderna COVID-19 vaccine is 72% effective at preventing symptomatic COVID-19 virus caused by the delta variant. One dose of the vaccine is also 96% effective at preventing severe disease with the COVID-19 virus caused by the delta variant.
- The Janssen/Johnson & Johnson COVID-19 vaccine is 85% effective at preventing severe disease with the COVID-19 virus caused by the delta variant, according to data released by Johnson & Johnson.
To strengthen protection against COVID-19 and circulating variants, the CDC recommends additional doses and booster doses of COVID-19 vaccines in specific instances:
- Additional dose. The CDC recommends a third dose of an mRNA COVID-19 vaccine for some people with weakened immune systems, such as those who have had an organ transplant. People with weakened immune systems might not develop enough immunity after vaccination with two doses of an mRNA COVID-19 vaccine. An additional dose might improve their protection against COVID-19.The third dose should be given at least 28 days after a second dose of an mRNA COVID-19 vaccine. The additional dose should be the same brand as the other two mRNA COVID-19 vaccine doses you were given. If the brand given isn’t known, either brand of mRNA COVID-19 vaccine can be given as a third dose.
- Booster dose. The CDC recommends a booster dose for some people who are fully vaccinated and whose immune response weakened over time. If you are age 18 or older, you have been given both doses of the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine and it’s been at least 6 months, you can get a single booster dose. If you are age 18 or older, you have been given one dose of the Janssen/Johnson & Johnson COVID-19 vaccine and it’s been at least 2 months, you also can get a single booster dose. You may choose which vaccine you get as a booster dose. You can get a booster dose that is the same brand as your previous shot or shots or choose a different brand.
COVID Variants: What You Should Know
In December 2020, news media reported a new variant of the coronavirus that causes COVID-19, and since then, other variants have been identified and are under investigation. The new variants raise questions: Are people more at risk for getting sick? Will the COVID-19 vaccines still work? Are there new or different things you should do now to stay safe?
Stuart Ray, M.D., vice chair of medicine for data integrity and analytics, and Robert Bollinger, M.D., M.P.H., Raj and Kamla Gupta professor of infectious diseases, are experts in SARS-CoV-2, the virus that causes COVID-19. They talk about what is known about these new variants, and answer questions and concerns you may have.
Coronavirus Mutation: Why does the coronavirus change?
Variants of viruses occur when there is a change — or mutation — to the virus’s genes. Ray says it is the nature of RNA viruses such as the coronavirus to evolve and change gradually. “Geographic separation tends to result in genetically distinct variants,” he says.
Mutations in viruses — including the coronavirus causing the COVID-19 pandemic — are neither new nor unexpected. Bollinger explains: “All RNA viruses mutate over time, some more than others. For example, flu viruses change often, which is why doctors recommend that you get a new flu vaccine every year.”
What is the delta variant?
Since the beginning of the COVID-19 pandemic, the SARS-CoV-2 coronavirus that causes COVID-19 has mutated (changed), resulting in different variants of the virus. One of these is called the delta variant (arising from Pango lineage B.1.617.2). The delta coronavirus is considered a “variant of concern” by the WHO and CDC because it appears to be more easily transmitted from one person to another. As of September 2021, delta is regarded as the most contagious form of the SARS-CoV-2 coronavirus so far.
Here is what you should know:
The CDC recommends that everyone wait until they are fully vaccinated for COVID-19 before traveling internationally. Traveling internationally if you are not fully vaccinated for COVID-19 is not recommended, because it puts you at risk for coronavirus infection, including the SARS-CoV-2 delta variant. This includes unvaccinated children.
- Delta rapidly became the dominant variant of the SARS-CoV-2 virus in the U.S. in 2021.
- Delta variant SARS-CoV-2, the virus that causes COVID-19, is now in most countries where SARS-CoV-2 is circulating, and people traveling internationally are likely to encounter it.
- Unvaccinated adults and children should strictly follow mask, distancing and hygiene safety precautions and avoid international travel if possible.
- Being fully vaccinated for COVID-19 can protect you from the delta variant, but breakthrough infections sometimes occur.
- All three of the F.D.A.-authorized COVID-19 vaccines can protect you from the delta variant. For Pfizer and Moderna vaccines, you need both doses for maximum protection. People should know that vaccines are very effective at preventing the most severe forms of COVID-19, but breakthrough infections can occur and caution is still warranted after becoming vaccinated.
- While the authorized COVID-19 vaccines are not perfect, they are highly effective against serious coronavirus disease and reduce the risk of hospitalization and death.
- Other vaccines available in other countries may not be as effective in protecting you from the delta variant and other mutations of the coronavirus.
- Although vaccines afford very high protection, infection with the delta and other variants remain possible. Fortunately, vaccination, even among those who acquire infections, appears to prevent serious illness, hospitalization and death from COVID-19.
How many strains of COVID are there?
“We are seeing multiple variants of the SARS-CoV-2 coronavirus that are different from the version first detected in China,” Ray says.
“Different variants have emerged in England, Brazil, California and other areas. More infectious variants such as beta, which first appeared in South Africa, may have increased ability to re-infect people who have recovered from earlier versions of the coronavirus, and also be somewhat resistant to some of the coronavirus vaccines in development. Still, vaccines currently used appear to offer significant protection from severe disease caused by coronavirus variants.”
What is a variant of concern?
Coronavirus variants are classified in different categories by organizations such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC).
A variant of interest is a coronavirus variant that, compared to earlier forms of the virus, has genetic characteristics that predict greater transmissibility, evasion of immunity or diagnostic testing or more severe disease.
A variant of concern has been observed to be more infectious, more likely to cause breakthrough or re-infections in those who are vaccinated or previously infected. These variants are more likely to cause severe disease, evade diagnostic tests, or resist antiviral treatment. Alpha, beta, gamma, and delta variants of the SARS-CoV-2 coronavirus are classified as variants of concern.
A variant of high consequence is a variant for which current vaccines do not offer protection. As of now, there are no SARS-CoV-2 variants of high consequence.
Will the COVID-19 vaccines work on the new variants?
Ray says, “There is evidence from laboratory studies that some immune responses driven by current vaccines could be less effective against some of these variants. The immune response involves many components, including B cells that make antibodies and T cells that can react to infected cells, and a reduction in one does not mean that the vaccines will not offer protection.
“People who have received the vaccines should watch for changes in guidance from the CDC [Centers for Disease Control and Prevention], and continue with coronavirus safety precautions to reduce the risk of infection, such as mask wearing, physical distancing and hand hygiene.”
“We deal with mutations every year for flu virus, and will keep an eye on this coronavirus and track it,” says Bollinger. “If there would ever be a major mutation, the vaccine development process can accommodate changes, if necessary,” he explains.
How are the new coronavirus variants different?
“There’s evidence that some genetic changes in SARS-CoV-2 can result in a more contagious variant,” Bollinger says. “This is particularly true for the delta variant.”
He notes that some of the mutations seem to affect the coronavirus’s spike protein, which covers the outer coating of SARS-CoV-2 and give the virus its characteristic spiny appearance. These proteins help the virus attach to human cells in the nose, lungs and other areas of the body.
“Researchers have preliminary evidence that some of the new variants seem to bind more tightly to our cells” Bollinger says. “This appears to make some of these new strains ‘stickier’ due to changes in the spike protein and therefore more easily transmitted.”
Are coronavirus variants more dangerous?
Bollinger says that some of these mutations may enable the coronavirus to spread faster from person to person, and more infections can result in more people getting very sick or dying. In addition, studies are underway to determine whether some variants could be associated with more severe disease.
“Therefore, it is very important for us to expand the number of genetic sequencing studies to keep track of these variants,” he says.
Bollinger explains that it may be more advantageous for a respiratory virus to evolve so that it spreads more easily. On the other hand, mutations that make a virus more deadly may not give the virus an opportunity to spread efficiently. “If we get too sick or die quickly from a particular virus, the virus has less opportunity to infect others. However, as we have seen with delta, more infections from a faster-spreading variant will lead to more hospitalizations and deaths,” he notes.
Could a new COVID-19 variant affect children more frequently than earlier strains?
Ray says that widespread infection with the delta variant has resulted in an increased number of cases in children, including uncommon severe infections and deaths.
“There is no convincing evidence that any of the variants have special propensity to infect or cause disease in children. We need to be vigilant in monitoring such shifts, but we can only speculate at this point,” he says.
Will there be more new coronavirus variants?
Yes. As long as the coronavirus spreads through the population, mutations will continue to happen, and the delta variant family continues to evolve.
“New variants of the SARS-CoV-2 virus are detected every week,” Ray says. “Most come and go — some persist but don’t become more common; some increase in the population for a while, and then fizzle out. When a change in the infection pattern first pops up, it can be very hard to tell what’s driving the trend — changes to the virus, or changes in human behavior. It is worrisome that similar changes to the spike protein are arising independently on multiple continents.”
Are there additional COVID-19 precautions for the new coronavirus variants?
Bollinger says that as of now, none of the new coronavirus variants call for any new prevention strategies. “We need to continue doing the basic precautions that we know work to interrupt spread of the virus,” he says.
Ray concurs: “There is no demonstration yet that these variants are biologically different in ways that would require any change in current recommendations meant to limit spread of COVID-19,” he says. “Nonetheless, we must continue to be vigilant for such phenomena. For now, the greater infectiousness we’re seeing means we must redouble our efforts using the preventative tools that we have in a multi-layered approach.”
Ray stresses that both vaccination and human behavior are important. “It is striking to note that the majority of COVID-19 deaths are now occurring in unvaccinated people, even when most adults in the USA have been vaccinated,” he says.
“The more people who are unvaccinated and infected, the more chances there are for mutations to occur. Limiting the spread of the virus through maintaining COVID-19 safeguards (mask wearing, physical distancing, practicing hand hygiene and getting vaccinated) gives the virus fewer chances to change. It also reduces the spread of more infectious variants, if they do occur.
“Vaccines are the medical miracle of 2020, but we need to re-emphasize basic public health measures, including masking, physical distancing, good ventilation indoors and limiting gatherings of people in close proximity with poor ventilation. We give the virus an advantage to evolve when we congregate in more confined spaces,” he says.
Regarding coronavirus variants, how concerned should we be?
“Most of the genetic changes we see in this virus are like the scars people accumulate over a lifetime — incidental marks of the road, most of which have no great significance or functional role,” Ray says. “When the evidence is strong enough that a viral genetic change is causing a change in the behavior of the virus, we gain new insight regarding how this virus works. The virus seems to have some limitations in its evolution – the advantageous mutations are drawn from a relatively limited menu – so there is some hope that we might not see variants that fully escape our vaccines.
“Updated versions of the current vaccines are being evaluated, but there is no clinical trial evidence yet that variant-specific vaccines would provide significantly greater protection. Though SARS-CoV-2 is changing gradually, it’s still much less genetically diverse than influenza.”
“As far as these variants are concerned, we don’t need to overreact,” Bollinger says. “But, as with any virus, changes are something to be watched, to ensure that testing, treatment and vaccines are still effective. The scientists will continue to examine new versions of this coronavirus’s genetic sequencing as it evolves.”
“In the meantime, we need to continue all of our efforts to prevent viral transmission and to vaccinate as many people as possible, and as soon as we can.”
WHO labels new Covid strain, named omicron, a ‘variant of concern,’ citing possible increased reinfection risk
The World Health Organization on Friday assigned the Greek letter omicron to a newly identified Covid variant in South Africa.
The U.N. health agency recognized the strain, first referred to as lineage B.1.1.529, as a variant of concern.
Health experts are deeply concerned about the transmissibility of the omicron variant given that it has an unusual constellation of mutations and a profile that is different from other variants of concern.
“Omicron, B.1.1.529, is named as a variant of concern because it has some concerning properties,” Maria Van Kerkhove, the WHO’s technical lead on Covid-19, said in a video published on Twitter. “This variant has a large number of mutations, and some of these mutations have some worrying characteristics.”
Experts fear that the sharp upswing of Covid cases in South Africa’s Gauteng province — where the heavily mutated strain of the virus was first identified — could mean it has greater potential to escape prior immunity than other variants. The number of omicron cases “appears to be increasing” in almost all of South Africa’s provinces, the WHO reported.
The organization only labels Covid strains as variants of concern when they’re more transmissible, more virulent or more adept at eluding public health measures, including vaccines and therapeutics. Data presented at a briefing Thursday hosted by South Africa’s Department of Health indicates that some of omicron’s mutations are connected with improved antibody resistance, which could reduce the protection offered by vaccines.
Certain mutations could also make omicron more contagious, while others haven’t been reported until now, preventing researchers from understanding how they could impact the strain’s behavior, according to a presentation at the briefing.
“Preliminary evidence suggests an increased risk of reinfection with this variant, as compared to other VOCs,” the WHO said in a statement released Friday.
The designation of a new variant of concern coupled with mounting alarm from health officials sent global markets into a tailspin Friday. Oil prices and travel and leisure stocks took heavy losses on the news.
WHO has said it will take weeks to understand how the variant may affect diagnostics, therapeutics and vaccines.
South African scientist Tulio de Oliveira said at a media briefing Thursday that the omicron variant contains around 50 mutations but more than 30 of these are in the spike protein, the region of the protein that interacts with human cells prior to cell entry.
What’s more, the receptor binding domain — the part of the virus that first makes contact with our cells — has 10 mutations, far greater than just two for the delta Covid variant, which spread rapidly earlier this year to become the dominant strain worldwide.
This level of mutation means it most likely came from a single patient who could not clear the virus, giving it the chance to genetically evolve. The same hypothesis was proposed for the Covid variant alpha.
“There’s a lot of work that is ongoing in South Africa and in other countries to better characterize the variant itself in terms of transmissibility, in terms of severity and any impact on our countermeasures, like the use of diagnostics, therapeutics or vaccines,” Van Kerkhove said. “So far there’s little information, but those studies are underway.”
Around 100 omicron variant genomes have been identified in South Africa, mostly in the Gauteng province. The variant has also been detected in Israel, Botswana and Hong Kong.
Many of the mutations identified in the omicron variant are linked to increased antibody resistance, which may reduce the effectiveness of vaccines and affect how the virus behaves with regard to inoculation, treatments and transmissibility, health officials have said.
Passengers wait at Frankfurt Airport.Boris Roessler | picture alliance | Getty Images
“There are two approaches to what happens next: Wait for more scientific evidence, or act now and row back later if it wasn’t required,” said Sharon Peacock, professor of public health and microbiology at the University of Cambridge.
“I believe that it is better to ‘go hard, go early and go fast’ and apologise if mistaken, than to take an academic view that we need to reach a tipping point in evidence before action is taken. Rapid spread in South Africa could be due to super-spreader events or other factors. But there are sufficient red flags to assume the worst rather than hope for the best — and take a precautionary approach,” Peacock said.
The European Union, the U.K., Israel, Singapore and the U.S. are among the countries imposing travel restrictions on southern African nations.
The WHO has cautioned countries against hastily imposing travel restrictions, saying they should instead take a “risk-based scientific approach.”
South Africa’s foreign ministry said Friday morning that the U.K.’s decision to take precautionary measures “seems to have been rushed as even the WHO is yet to advise on the next steps.”
What are the Covid variants and will vaccines still work?
A new heavily mutated version of coronavirus has been found that scientists say is of “great concern”.
One of most pressing questions is will vaccines still work?
What is this new variant?
There are thousands of different types, or variants, of Covid circulating across the world. That’s to be expected because viruses mutate all the time.
But this new variant, called B.1.1.529 or Omicron, has experts particularly worried because it is very different to the original Covid, which current vaccines were designed to fight.
It has a long list of genetic changes – 50 in all. Of these, 32 are in the spike protein of the virus – the part which is the target of vaccines.
However, it is too soon to know how much of a threat it poses.
Will vaccines still work?
Current vaccines are not an ideal match so might not work quite as well, say experts.
But that doesn’t mean they’ll offer zero protection.
Remember, vaccines are still very effective at protecting lives by cutting the risk of severe illness against other major Covid variants, including Delta, Alpha, Beta and Gamma.ADVERTISEMENT
Doctors say it is vital people get the recommended number of doses to gain maximum protection against existing and emerging variants.
In the UK, booster jabs are recommended for:
- Frontline health and social care workers
- Older adults in residential care homes
- People aged 16-49 years old with underlying health conditions which put them at greater risk of severe Covid
- Adults who share a household with vulnerable people
More than 16m booster or third doses have been given so far in the UK.
Although Covid infections have been rising again across the UK, the number of hospitalisations and deaths has remained well below the levels seen in earlier waves. Experts say this is because of the success of the vaccine programme.
Scientists will be running lots of tests to check if the vaccines will hold up against this latest variant.
It is early days, but experts will study potentially important mutations that might make it more infectious and able to sidestep some of the protection given by vaccines.
And they will assess if it is causing more serious disease than other variants.
How quickly could we get new vaccines against variants?
Updated versions of vaccines against Covid variants are already being designed and tested, in case they are needed at some point.
Should that time arrive, a new vaccine could be ready within weeks, to run checks on.
Manufacturers could scale up production quickly too and regulators have already discussed how to fast track the approval process.
No corners would be cut, but the whole process – from design to approval – could be much faster than when Covid vaccines were first launched.
What about the other variants?
Officials have a close watch on a few.
The most potentially dangerous ones are called variants of concern and include:
- Delta (B.1.617.2), first identified in India and now the most common type circulating in the UK
- Alpha (B.1.1.7), first identified in the UK but which spread to more than 50 countries
- Beta (B.1.351), first identified in South Africa but which has been detected in at least 20 other countries, including the UK
- Gamma (P.1), first identified in Brazil but which has spread to more than 10 other countries, including the UK
UK officials are also keeping an eye on a recent descendent of the Delta variant, called AY.4.2 or “Delta plus”.
How dangerous are variants?
There is no evidence that any of them cause more serious illness for the vast majority of people.
As with original Covid, the risk remains highest for people who are elderly or have significant underlying health conditions.
But even so, if a variant is more infectious it will lead to more deaths in an unvaccinated population.
Vaccines offer high protection against severe illness with Covid-19, including infections caused by variants of concern. The shots also reduce the risk of infection. But they do not completely eliminate all risk.
The advice to avoid infection remains the same for all strains: wash your hands, keep your distance, wear a face covering in crowded places and be vigilant about ventilation.
Why are variants occurring?
Viruses make carbon copies of themselves to reproduce but they aren’t perfect at it. Errors can creep in that change the genetic blueprint, resulting in a new version or variant.
If this gives the virus a survival advantage, the new version will thrive.
The more chances coronavirus has to make copies of itself in us – the host – the more opportunities there are for mutations to occur.
That’s why keeping infections down is important. Vaccines help by cutting transmission as well as protecting against serious Covid illness.
Experts say it is possible that the new highly altered variant B.1.1.529 may have originated in a patient whose immune system was unable to get rid of a Covid infection quickly, giving the virus more time to morph.
There’s Always Going To Be Another Variant
Just when you thought it was safe to live your life again, a new coronavirus variant has emerged. “Omicron,” the fifteenth letter of the Greek alphabet and thirteenth iteration of COVID-19, which conspicuously skipped over the letter “Xi”, threatens to keep us all locked down just a little bit longer to “slow the spread” and “flatten the curve” while public health officials do their darnedest to eradicate the virus, which they will never succeed at doing because there will always be another variant.
Viruses mutate. Viruses that contain RNA as their genetic material, such as coronaviruses and influenza, mutate even more than others. There are four species of influenza, each comprising dozens of subtypes and hundreds of subtype combinations. Despite widespread annual vaccinations and the best efforts of public health experts, influenza continues to spread, as it has since antiquity, and to kill upwards of 650,000 people each year.
At least some part of COVID-19 appears to have originated in bats, making eradication even less likely. As Michael Osterholm, an epidemiologist at the University of Minnesota, explained to the scientific journal Science, “There is no disease in the history of humankind that has disappeared from the face of the Earth when zoonotic disease was such an important part of, or played a role in, the transmission.” In other words, COVID-19—like influenza and the coronaviruses that cause the common cold—is here to stay.
Even if biology had not fated endless COVID variants, politics would have. Powerful interests in elected government, the administrative state, and putatively private enterprise seized upon the coronavirus to grow their wealth and power. So despite a low infection fatality rate, widespread vaccines, and effective treatments, our cynical ruling class has every incentive to prolong the sense of crisis.
“I think we need to just get our mindset that the virus is still in control,” warns William Schaffner, an epidemiologist at the University of Minnesota. “I don’t care about your COVID fatigue.” But the virus is not in control of anything; people are. In the old American republic, the people controlled the government through their elected representatives within boundaries set by the Constitution. In the new American oligarchy, unaccountable technocrats restructure society according to their own whims no matter what the people want, and they justify their rule by the dubious claim that they represent “science.”
The more COVID mutates, the more the symptoms remain the same: cough, fever, and the loss of our rights and way of life, which unlike our senses of smell and taste will not return once we have recovered from the virus. Biological science ensures that the “omicron” variant will become the “pi,” then the “rho,” then the “sigma,” and so on. Political science ensures that our rulers will exploit each new variant to maintain the power they’ve already taken, to scare the people into submission, and to seize whatever else they can squeeze out of us.
Why you shouldn’t panic over the Omicron variant
The new variant of concern has a large number of mutations and is spreading fast. But experts say there are many unknowns, and that vaccines and masks are still the best available protections.
Experts warned that regions with low vaccination rates could allow the virus that causes COVID-19 to evolve more rapidly, possibly yielding a more transmissible or antibody-resistant variant that would escalate the pandemic. Now this prediction may have come true.
Last week the World Health Organization named a new SARS-CoV-2 variant Omicron and classified it as a variant of concern, along with Alpha, Beta, Gamma, and Delta. The variant was discovered in South Africa, where just 23 percent of the population is vaccinated, due in part to most supplies going to North America and Europe. However, at this early stage there is still a lot scientists can’t say for sure about Omicron and its potential to worsen the COVID-19 pandemic. So far most breakthrough cases involving this variant seem to be mild, and it’s unclear how much the mutations will erode vaccine efficacy. It is also unknown whether Omicron will cause more severe illness than Delta.
Preliminary evidence from South Africa suggests that Omicron might be more transmissible than previous variants: Positive cases in the Tshwane region of Gauteng Province—where Omicron was first detected on November 9—increased from less than one percent to more than 30 percent of collected samples in the past three weeks. Omicron now makes up 76 percent of all SARS-CoV-2 sequenced in South Africa, making it the most prevalent variant in the country. It is replacing other variants faster than Delta replaced Beta.
“[It is] a reminder we have this new variant as a result of failure to control infections,” says Ravi Gupta, a clinical microbiologist at the University of Cambridge who is one of the world’s leading researchers on COVID-19.
Omicron shares many key mutations with previous variants of concern, but it has also accumulated a dozen novel mutations on its spike protein, the part of the virus that is essential for infecting human cells. The new variant has 32 mutations in this region overall, and scientists fear the large number might diminish the ability of existing antibodies to neutralize the variant, making current vaccines less effective.
“It has mutations at virtually every site that current antibodies would bind to,” says Michael Worobey, who studies the evolution of viruses at the University of Arizona. There are also mutations that could make Omicron infect cells faster and transmit from person to person more easily. “This one is worrying, and I’ve not said that since Delta,” says Gupta.
“While we know there are many mutations, in the case of this [Omicron] variant, we don’t yet know what their overall effect is,” cautions Kei Sato, a virologist at the University of Tokyo. Only about 1,000 people have been diagnosed with Omicron, and scientists currently have very few samples and genetic sequences from South Africa, which makes it difficult for experts to draw firm conclusions about Omicron’s contagiousness and whether it causes more severe disease.
On the bright side, antibodies taken from people who were first naturally infected and then vaccinated were still able to neutralize a synthetic Omicron-type virus in the laboratory. That suggests a booster dose of an mRNA vaccine may still provide robust protection against Omicron.
Omicron “is a cause for concern, not a cause for panic,” U.S. President Joe Biden said in a press briefing on Monday morning. “The best protection against this new variant or any of the various out there, the ones we’ve been dealing with already, is getting fully vaccinated and getting a booster shot.”
For now, “we have every indication that the vaccines are still effective in preventing severe disease and or complications,” says Ian Sanne, an infectious diseases specialist at University of Witwatersrand in Johannesburg, South Africa. “The data, however, is small and early.”
Omicron’s worrisome mutations
When an individual encounters the SARS-CoV-2 virus, the body’s immune cells produce antibodies that target the spike protein, the part the virus uses to attach to the ACE2 receptor protein on human cells and infect them. When antibodies bind to the spike, the virus is blocked from entering the cell. Because the spike is essential for infection, all currently authorized vaccines use it to train the body’s immune response.
The 32 mutations that occur in Omicron’s spike gene can be organized into three groups, depending on how they alter the function of the spike protein, says Olivier Schwartz, a virologist and immunologist at the Pasteur Institute in France.
Some mutations enhance the spike protein’s ability to bind to the human ACE2 receptor; some help the surface of the virus fuse with the cell and allow the virus to enter; others alter the appearance of the spike protein, making it harder to recognize and allowing the virus to evade antibodies.
Of the many mutations on Omicron’s spike, the loss of amino acids at positions 69 and 70 makes the virus twice as infectious as the original virus. But in a stroke of luck, these two mutations are not present in Delta, making Omicron easy to distinguish in a widely used PCR assay.
The University of Cambridge’s Gupta has previously shown that these deleted amino acids, along with a third mutation at position 796 on the spike protein, are associated with Alpha’s ability to evade the body’s immune response. This suggests these same three mutations could help Omicron escape existing immunity either from vaccines or previous infections—and some preliminary evidence suggests that is happening.
“To date there have been a number of breakthrough infections, but they have been mild,” says Barry Schoub, a virologist and adviser on COVID-19 vaccines to South Africa’s government. However, experts say it is too early to know whether Omicron causes more severe disease as there is a lag between infection and hospitalization.
Another cluster of mutations in Omicron at positions 655, 679 and 681 of the spike protein are thought to help the virus infect human cells more easily; they also exist in the Mu variant and are known to enhance its transmissibility.
Additionally, in a study not yet peer reviewed, researchers suggest that a mutation that Omicron shares with Alpha and Mu might help it replicate faster and resist immunity. And a mutation at the 501 position also found in Alpha, Beta, and Gamma makes the spike protein attach more tightly to the ACE2 receptor, making the virus more efficient at infecting cells.
“We see this virus spreading pretty rapidly in a population with, we think, very high levels of immunity,“ says Richard Lessells, infectious diseases specialist at the University of KwaZulu-Natal in Durban, South Africa. “That’s what gives us concern,” he adds. “[Omicron] could have kind of more immune evasion than previous variants.”
In the Gauteng region of South Africa, blood samples suggest 80 percent of the population already had some immunity because of encounters with previous SARS-CoV-2 variants. That’s why experts are worried about the rapid rise of Omicron, which accounted for 76 percent of cases in just a couple of weeks. By comparison, it took Delta several months to reach that level of prevalence.
The number of COVID-19 hospitalizations in South Africa has also risen sharply within the last month, but whether that is due to overall numbers of people becoming infected or due to specific infection with Omicron is not yet clear.
“There’s not enough information available yet to make a conclusion about the severity of Omicron in comparison to other variants,” says Ben Cowling, an epidemiologist at the University of Hong Kong. That’s because most early cases are among university students and younger people, who generally develop more mild disease.
With current data, it’s also not clear whether the growth advantage of Omicron over Delta is because of its ability to escape immunity by reinfecting previously immune people, or by infecting individuals who haven’t been exposed to the virus, notes Tom Wenseleers, an evolutionary biologist and biostatistician at the KU Leuven University in Belgium.
While the number of people testing positive in areas of South Africa affected by Omicron has risen sharply, there is not enough data to conclude whether that is entirely due to Omicron or to superspreader events among students and young people.
Despite the worrying rise in cases, preliminary data, including studies from Theodora Hatziioannou’s lab in New York, suggest that vaccines and boosters are still powerful tools against the virus.
Researchers led by Hatziioannou, of the Rockefeller University in New York, created a synthetic version of the virus that contained many of the spike protein mutations that Omicron carries. They found that neutralizing antibodies from people who had recovered from COVID-19 and then got an mRNA vaccine dose were able to fend off the mutated synthetic virus.
However, it takes between two and three weeks after infection for COVID-19 to develop and the severity of the disease to be gauged, explains Sanne, which means it will take time to determine whether the existing vaccines hold up against Omicron in the real world.
In the meantime, the best way to avoid any type of infection from Omicron or any other variant is to get more people vaccinated and for governments to continue promoting public health measures such as social distancing and mask wearing. “Please get vaccinated and boosted and mask up in public, as the mutations in this virus likely result in high-level escape from neutralizing antibodies,” says Gupta.
“The primary way to minimize the emergence of new variants is to limit ongoing transmissions,” adds Ridhwaan Suliman, a senior researcher at the Council for Scientific and Industrial Research in South Africa. “Viruses can’t mutate if they can’t replicate.”
How bad is Omicron? What scientists know so far
COVID researchers are working at breakneck speed to learn about the variant’s transmissibility, severity and ability to evade vaccines.
Barely a week has elapsed since scientists in Botswana and South Africa alerted the world to a fast-spreading SARS-CoV-2 variant now known as Omicron. Researchers worldwide are racing to understand the threat that the variant — now confirmed in more than 20 countries — poses to the world. Yet it might take scientists weeks to paint a more complete picture of Omicron, and to gain an understanding of its transmissibility and severity, as well as its potential to evade vaccines and cause reinfections.Heavily mutated Omicron variant puts scientists on alert
“Wherever I go, everyone says: tell us more about Omicron,” says Senjuti Saha, a molecular microbiologist and director of the Child Health Research Foundation in Dhaka, Bangladesh. “There is so little understanding of what’s going on, and that’s true, even for scientists.”
Nature rounds up what scientists know so far about the Omicron variant.
How fast is Omicron spreading?
Omicron’s rapid rise in South Africa is what worries researchers most, because it suggests the variant could spark explosive increases in COVID-19 cases elsewhere. On 1 December, South Africa recorded 8,561 cases, up from the 3,402 reported on 26 November and several hundred per day in mid-November, with much of the growth occurring in Gauteng Province, home to Johannesburg.
Epidemiologists measure an epidemic’s growth using R, the average number of new cases spawned by each infection. In late November, South Africa’s National Institute for Communicable Diseases (NICD) in Johannesburg determined that R was above 2 in Gauteng. That level of growth was last observed in the early days of the pandemic, Richard Lessels, an infectious-disease physician at KwaZulu-Natal University in Durban, South Africa, told a press briefing last week.
Gauteng’s R value was well below 1 in September — when Delta was the predominant variant and cases were falling — suggesting that Omicron has the potential to spread much faster and infect vastly more people than Delta, says Tom Wenseleers, an evolutionary biologist at the Catholic University of Leuven in Belgium. Based on the rise in COVID-19 cases and on sequencing data, Wenseleers estimates that Omicron can infect three to six times as many people as Delta, over the same time period. “That’s a huge advantage for the virus — but not for us,” he adds.
Researchers will be watching how Omicron spreads in other parts of South Africa and globally to get a better read on its transmissibility, says Christian Althaus, a computational epidemiologist at the University of Bern, Switzerland. Heightened surveillance in South Africa could cause researchers to overestimate Omicron’s fast growth. But if this pattern is repeated in other countries, it would be very strong evidence that Omicron has a transmission advantage, adds Althaus. “If it doesn’t happen, for example, in European countries, it means things are a bit more complex and strongly depend on the immunological landscape. So we have to wait.”
Although genome sequencing is needed to confirm Omicron cases, some PCR tests can pick up a hallmark of the variant that distinguishes it from Delta. On the basis of this signal, there are preliminary indications that cases, although extremely low in number, are rising in the United Kingdom. “That’s certainly not what we want to see right now and suggests that Omicron could indeed also have a transmission advantage in the UK,” Althaus adds.
Can Omicron overcome immunity from vaccines or infection?
The variant’s swift rise in South Africa hints that it has some capacity to evade immunity. Around one-quarter of South Africans are fully vaccinated, and it’s likely that a large fraction of the population was infected with SARS-CoV-2 in earlier waves, says Wenseleers, based on heightened death rates since the start of the pandemic.
In this context, Omicron’s success in southern Africa might be due largely to its capacity to infect people who recovered from COVID-19 caused by Delta and other variants, as well as those who’ve been vaccinated. A 2 December preprint1 from researchers at the NICD found that reinfections in South Africa have increased as Omicron has spread. “Unfortunately, this is the perfect environment for immune-escape variants to develop,” says Althaus.
How well the variant spreads elsewhere might depend on factors such as vaccination and previous infection rates, says Aris Katzourakis, who researches viral evolution at the University of Oxford, UK. “If you throw it into the mix in a highly vaccinated population that has given up on other control measures, it might have the edge there.”Omicron-variant border bans ignore the evidence, say scientists
Researchers want to measure Omicron’s ability to evade immune responses and the protection they offer. For instance, a team led by Penny Moore, a virologist at the NICD and the University of the Witwatersrand in Johannesburg, is measuring the ability of neutralizing, or virus-blocking, antibodies triggered by previous infection and vaccination to stop Omicron from infecting cells. To test this in the laboratory, her team is making ‘pseudovirus’ particles — an engineered version of HIV that uses SARS-CoV-2’s spike protein to infect cells — that match Omicron, which harbours as many as 32 changes to spike.
Another South Africa-based team, led by virologist Alex Sigal at the Africa Health Research Institute in Durban, is conducting similar tests of virus-neutralizing antibodies using infectious SARS-CoV-2 particles. So is a team led by Pei-Yong Shi, a virologist at the University of Texas Medical Branch in Galveston, who is collaborating with the makers of the Pfizer–BioNTech vaccine to determine how it holds up against Omicron. “I was really very concerned when I saw the constellation of mutations in the spike,” he says. “We just have to wait for the results.”
Previous studies of Omicron’s spike mutations — particularly in the region that recognizes receptors on human cells — suggest that the variant will blunt the potency of neutralizing antibodies. For instance, in a September 2021 Nature paper2, a team co-led by Paul Bieniasz, a virologist at Rockefeller University in New York City, engineered a highly mutated version of spike — in a virus incapable of causing COVID-19 — that shares numerous mutations with Omicron. The ‘polymutant spike’ proved fully resistant to neutralizing antibodies from most of the people they tested, who had either received two doses of an mRNA vaccine or recovered from COVID-19. With Omicron, “we expect there to be a significant hit”, says Bieniasz.
How will vaccines fare against Omicron?
If Omicron can dodge neutralizing antibodies, it does not mean that immune responses triggered by vaccination and prior infection will offer no protection against the variant. Immunity studies suggest that modest levels of neutralizing antibodies may protect people from severe forms of COVID-19, says Miles Davenport, an immunologist at the University of New South Wales in Sydney, Australia.
Other aspects of the immune system, particularly T cells, may be less affected by Omicron’s mutations than are antibody responses. Researchers in South Africa plan to measure the activity of T cells and another immune player called natural killer cells, which might be especially important for protection against severe COVID-19, says Shabir Madhi, a vaccinologist at the University of the Witwatersrand.
Madhi, who has led COVID-19 vaccine trials in South Africa, is also part of efforts to conduct epidemiological studies of vaccines’ effectiveness against Omicron. There are anecdotal reports of breakthrough infections involving all three vaccines that have been administered in South Africa — Johnson & Johnson, Pfizer–BioNTech and Oxford–AstraZeneca. But Madhi says researchers will want to quantify the level of protection against Omicron provided by vaccines, as well as by previous infection.
He suspects that the results will be reminiscent of how the AstraZeneca–Oxford vaccine performed against the Beta variant, an immune-evading variant that was identified in South Africa in late 2020. A trial led by Madhi found that the vaccine offered little protection against mild and moderate disease, while a real-world analysis in Canada showed greater than 80% protection against hospitalization.
If Omicron behaves similarly, Madhi says, “we’re going to see a surge of cases. We’re going to see lots of breakthrough infections, lots of reinfections. But there’s going to be this unhinging of the case rate in the community compared to the hospitalization rate”. Early reports suggest that most breakthrough infections with Omicron have been mild, says Madhi. “For me, that is a positive signal.”
Will current boosters improve protection against Omicron?
The threat of Omicron has prompted some rich countries, such as the United Kingdom, to accelerate and broaden the roll-out of COVID vaccine booster doses. But it’s not yet clear how effective these doses will be against this variant.
Third doses supercharge neutralizing-antibody levels, and it’s likely that this will provide a bulwark against Omicron’s ability to evade these antibodies, says Bieniasz. His team’s work on the polymutant spike found that people who had recovered from COVID-19 months before receiving their jabs had antibodies capable of blocking the mutant spike. To Bieniasz, those results suggest that people with repeated exposure to SARS-CoV-2’s spike protein, be it through infection or a booster dose, are “quite likely to have neutralizing activity against Omicron”.
Does Omicron cause milder or more severe disease than previous variants?
Early reports linked Omicron with mild disease, raising hopes that the variant might be less severe than some of its predecessors. But these reports — which are often based on anecdotes or scant scraps of data — can be misleading, cautions Müge Çevik, an infectious-disease specialist at the University of St Andrews, UK. “Everyone is trying to find some data that could guide us,” she says. “But it’s very difficult at the moment.”
A major challenge when assessing a variant’s severity is how to control for the many confounding variables that can influence the course of disease, particularly when outbreaks are geographically localized. For example, reports of mild disease from Omicron infection in South Africa could reflect the fact that the country has a relatively young population, many of whom have already been exposed to SARS-CoV-2.
During the early days of the Delta outbreak, there were reports that the variant was causing more serious illness in children than did other variants — an association that dissolved once more data were collected, Çevik says.
Researchers will be looking for data on Omicron infections in other countries. This geographical spread, and a larger sample size as cases accrue, will give researchers a better idea of how generalizable the early reports of mild disease might be. Ultimately, researchers will want to conduct case-controlled studies, in which two groups of participants are matched in terms of important factors such as age, vaccination status and health conditions. Data from both groups will need to be collected at the same time, because the number of hospitalizations can be influenced by overall hospital capacity in a region.
And, crucially, researchers will need to control for the level of economic deprivation. A rapidly spreading new variant may reach vulnerable groups more rapidly, Çevik says, by nature of their work or living conditions. And such groups often experience more severe disease.
All of this will take time. “I think the severity question will be one of the last bits that we’ll be able to untangle,” she says. “That’s how it happened with Delta.”
Where has Omicron spread and how are scientists tracking it?
More countries are detecting the Omicron variant, but the capacity to rapidly sequence viruses from positive COVID-19 tests is concentrated in wealthy countries, meaning that early data on Omicron’s spread will be skewed.
Surveillance efforts in Brazil and some other countries are taking advantage of a distinctive result on a particular PCR test that could allow them to pinpoint potential Omicron cases for sequencing, says virologist Renato Santana at the Federal University of Minas Gerais in Brazil. The test looks for segments of three viral genes, one of which is the gene that encodes for the spike protein. Mutations in Omicron’s spike gene prevent its detection in the test, meaning that samples containing the variant will test positive for only two of the genes.
Even so, not everyone uses that test and it could take some time before Omicron’s spread is fully mapped. Despite some guidelines urging countries to sequence 5% of their samples that test positive for SARS-CoV-2, few can afford to do so, says computational virologist Anderson Brito at the All for Health Institute in São Paulo, Brazil. And Brito worries that the travel bans enacted by some countries against South Africa, and other southern African nations, in the wake of its Omicron discovery could discourage governments from sharing genomic surveillance data. “We are punishing those who did a good job,” he says.
In Bangladesh, which sequences about 0.2% of positive coronavirus samples, researchers would be eager to ramp up sequencing to keep tabs on Omicron and other emerging variants, says Saha. But resources are limited. Bangladesh is recovering from a large dengue outbreak, she adds. “In the global south, we are all worried about COVID, but let’s not forget our endemic diseases,” Saha says. “We can only do so many.”
Beyond Omicron: what’s next for COVID’s viral evolution
The rapid spread of new variants offers clues to how SARS-CoV-2 is adapting and how the pandemic will play out over the next several months
As the world sped towards a pandemic in early 2020, evolutionary biologist Jesse Bloom gazed into the future of SARS-CoV-2. Like many virus specialists at the time, he predicted that the new pathogen would not be eradicated. Rather, it would become endemic — the fifth coronavirus to permanently establish itself in humans, alongside four ‘seasonal’ coronaviruses that cause relatively mild colds and have been circulating in humans for decades or more.
Bloom, who is based at the Fred Hutchinson Cancer Research Center in Seattle, Washington, saw these seasonal coronaviruses as potentially providing a roadmap for how SARS-CoV-2 might evolve and for the future of the pandemic. But little is known about how these other viruses continue to thrive. One of the best-studied examples — a seasonal coronavirus called 229E — infects people repeatedly throughout their lives. But it’s not clear whether these reinfections are the result of fading immune responses in their human hosts or whether changes in the virus help it to dodge immunity. To find out, Bloom got hold of decades-old blood samples from people probably exposed to 229E, and tested them for antibodies against different versions of the virus going back to the 1980s.
The results were striking1. Blood samples from the 1980s contained high levels of infection-blocking antibodies against a 1984 version of 229E. But they had much less capacity to neutralize a 1990s version of the virus. They were even less effective against 229E variants from the 2000s and 2010s. The same held true for blood samples from the 1990s: people had immunity to viruses from the recent past, but not to those from the future, suggesting that the virus was evolving to evade immunity.
“Now that we’ve had almost two years to see how SARS-CoV-2 evolves, I think there are clear parallels with 229E,” says Bloom. Variants such as Omicron and Delta carry mutations that blunt the potency of antibodies raised against past versions of SARS-CoV-2. And the forces propelling this ‘antigenic change’ are likely to grow stronger as most of the planet gains immunity to the virus through infection, vaccination or both. Researchers are racing to characterize the highly mutated Omicron variant. But its rapid rise in South Africa suggests that it has already found a way to dodge human immunity.How bad is Omicron? What scientists know so far
How SARS-CoV-2 evolves over the next several months and years will determine what the end of this global crisis looks like — whether the virus morphs into another common cold or into something more threatening such as influenza or worse. A global vaccination push that has delivered nearly 8 billion doses is shifting the evolutionary landscape, and it’s not clear how the virus will meet this challenge. Meanwhile, as some countries lift restrictions to control viral spread, opportunities increase for SARS-CoV-2 to make significant evolutionary leaps.
Scientists are searching for ways to predict the virus’s next moves, looking to other pathogens for clues. They are tracking the effects of the mutations in the variants that have arisen so far, while watching out for new ones. They expect SARS-CoV-2 eventually to evolve more predictably and become like other respiratory viruses — but when this shift will occur, and which infection it might resemble is not clear.
Researchers are learning as they go, says Andrew Rambaut, an evolutionary biologist at the University of Edinburgh, UK. “We haven’t had much to go on.”
An early plateau
Scientists tracking the evolution of SARS-CoV-2 are looking out for two broad categories of changes to the virus. One makes it more infectious or transmissible, for instance by replicating more quickly so that it spreads more easily through coughs, sneezes and wheezes. The other enables it to overcome a host’s immune response. When a virus first starts spreading in a new host, the lack of pre-existing immunity means that there is little advantage to be gained by evading immunity. So, the first — and biggest — gains a new virus will make tend to come through enhancements to infectivity or transmissibility.
“I was thoroughly expecting that this new coronavirus would adapt to humans in a meaningful way — and that would probably mean increased transmissibility,” says Wendy Barclay, a virologist at Imperial College London.
Genome sequencing early in the pandemic showed the virus diversifying and picking up about two single-letter mutations per month. This rate of change is about half that of influenza and one-quarter that of HIV, thanks to an error-correcting enzyme coronaviruses possess that is rare among other RNA viruses. But few of these early changes seemed to have any effect on the behaviour of SARS-CoV-2, or show signs of being favoured under natural selection.
An early mutation called D614G within the gene encoding the virus’s spike protein — the protein responsible for recognizing and penetrating host cells — seemed to offer a slight transmissibility boost2. But this gain was nothing like the leaps in transmissibility that researchers would later observe with the variants Delta and Alpha, says Sarah Otto, an evolutionary biologist at the University of British Columbia in Vancouver, Canada.
Otto sees the virus’s evolution as like walking in a landscape, where higher elevations equate to improved transmissibility. The way she sees it, when SARS-CoV-2 began spreading in humans it seemed to be on a ‘fitness plateau’ surrounded by a landscape of many possible evolutionary outcomes. In any given infection, there were probably thousands of viral particles each with unique single-letter mutations, but Otto suspects that few, if any, of these made the virus more infectious. Most changes probably reduced transmissibility.
“If the virus entered at a reasonably high point, any one-step mutation would take it downhill,” Otto says. Summiting higher peaks required the combinations of several mutations to make more-significant gains in its ability to spread.
Reaching new heights
In late 2020 and early 2021, there were signs that SARS-CoV-2 had scaled some distant peaks. Researchers in the United Kingdom spotted a variant called B.1.1.7 that contained numerous mutations in its spike protein. “It was a bit unusual because it seemed to come out of nowhere,” says Francois Balloux, a computational biologist at University College London.
That variant — since renamed Alpha — spread at least 50% faster than earlier circulating lineages. UK public-health officials linked it to a mysterious rise in cases in southeast England during a national lockdown in November 2020. Around the same time, virus hunters in South Africa linked another mutation-laden variant called B.1.351 — now known as Beta — to a second wave of infections there. Not long after, a highly transmissible variant, now called Gamma, was tracked to Amazonas state in Brazil.
These three ‘variants of concern’ share some mutations, particularly in key regions of the spike protein involved in recognizing the host-cell ACE2 receptors that the virus uses to enter cells. They also carried mutations similar or identical to those spotted in SARS-CoV-2 in people with compromised immune systems whose infections lasted for months. This led researchers to speculate that long-term infections might allow the virus to explore different combinations of mutations to find ones that are successful. Typical infections lasting days offer fewer opportunities. Super-spreading events, where large numbers of people are infected, might also explain why some variants flourished and others fizzled out.
Whatever their origins, all three variants seemed to be more infectious than the strains they displaced. But Beta and Gamma also contained mutations that blunted the potency of infection-blocking ‘neutralizing’ antibodies triggered by previous infection or vaccination. This raised the possibility that the virus was beginning to behave in the ways predicted by Bloom’s studies of 229E.
The three variants spread around the world, particularly Alpha, which sparked new waves of COVID-19 as it came to dominate in Europe, North America, the Middle East and beyond (see ‘Variant waves’). Many researchers expected that a descendant of Alpha — which seemed to be the most infectious of the bunch — would pick up additional mutations, such as those that evade immune responses, to make it even more successful. “That absolutely proved not to be the case,” says Paul Bieniasz, a virologist at Rockefeller University in New York City. “Delta came out of left field.”
The Delta dilemma
The Delta variant was identified in India’s Maharashtra state during a ferocious wave of COVID-19 that hit the country in the spring of 2021, and researchers are still taking stock of its consequences for the pandemic. Once it arrived in the United Kingdom, the variant spread quickly and epidemiologists determined that it was about 60% more transmissible than Alpha, making it several times as infectious as the first circulating strains of SARS-CoV-2. “Delta is kind of a super-Alpha,” says Barclay. “I think the virus is still looking for solutions to adapt to the human host.”
Studies from Barclay’s laboratory and others suggest that Delta made significant gains in its fitness by improving its ability to infect human cells and spread between people3,4. Compared with other variants, including Alpha, Delta multiplies faster and to higher levels in the airways of infected individuals, potentially outpacing initial immune responses against the virus.
Yet researchers expect such gains to become ever smaller. Scientists measure a virus’s inherent ability to spread in an immunologically naive population (that is, unvaccinated and not exposed to the virus previously) by a number called R0, which is the average number of people an infected person infects. Since the start of the pandemic this figure has jumped as much as threefold. “At some point, I would expect that increased transmissibility will stop happening,” says Bloom. “It’s not going to become infinitely transmissible.” Delta’s R0 is higher than seasonal coronaviruses and influenza, but still lower than that of polio or measles.
Other established human viruses do not make the leaps in infectivity that SARS-CoV-2 has in the past two years, and Bloom and other scientists expect the virus to eventually behave in the same way. Trevor Bedford, an evolutionary biologist at the Fred Hutchinson, says the virus must balance its ability to replicate to high levels in people’s airways with the need to keep them healthy enough to infect new hosts. “The virus doesn’t want to put someone in bed and make them sick enough that they’re not encountering a number of other people,” he says. One way for the virus to thread this needle would be to evolve to grow to lower levels in people’s airways, but maintain infections for a longer period of time, increasing the number of new hosts exposed to the virus, says Rambaut. “Ultimately there’s going to be trade-off between how much virus you can produce and how quickly you elicit the immune system.” By lying low, SARS-CoV-2 could ensure its continued spread.
If the virus evolved in this way, it might become less severe, but that outcome is far from certain. “There’s this assumption that something more transmissible becomes less virulent. I don’t think that’s the position we should take,” says Balloux. Variants including Alpha, Beta and Delta have been linked to heightened rates of hospitalization and death — potentially because they grow to such high levels in people’s airways. The assertion that viruses evolve to become milder “is a bit of a myth”, says Rambaut. “The reality is far more complex.”
The rise of Omicron
Delta and its descendants now account for the vast majority of COVID-19 cases worldwide. Most researchers expected these Delta lineages to eventually outcompete the last holdouts. But Omicron has undermined those predictions. “A lot of us were expecting the next weird variant to be a child of Delta, and this is a bit of a wild card,” says Aris Katzourakis, a specialist in viral evolution at the University of Oxford, UK. Teams in Botswana and South Africa identified the variant in late November — although researchers say it is unlikely to have originated in either country — and health officials have linked it to a rapidly growing outbreak centred in South Africa’s Gauteng province. The variant harbours around 30 changes to spike, many shared with the other variants of concern, and scientists worldwide are working to gauge the threat it poses.
The swift rise in cases of Omicron in South Africa suggests that the new variant has a fitness advantage over Delta, says Tom Wenseleers, an evolutionary biologist and biostatistician at the Catholic University of Leuven in Belgium. Omicron carries some of the mutations associated with Delta’s sky-high infectivity. But if increased infectivity were the sole reason for its rapid growth, it would translate to an R0 in the 30s, Wenseleers says. “That’s very implausible.”
Instead, he and other researchers suspect that Omicron’s rise may be largely due to its ability to infect people who are immune to Delta through vaccination or previous infection.
Scientists’ portrait of Omicron is still blurry and it will take weeks before they can fully assess its properties. But if the variant is spreading, in part, because of its ability to evade immunity, it fits in with theoretical predictions about how SARS-CoV-2 is likely to evolve, says Sarah Cobey, an evolutionary biologist at the University of Chicago in Illinois.
As gains in SARS-CoV-2’s infectivity start to slow, the virus will have to maintain its fitness through overcoming immune responses, says Cobey. For instance, if a mutation or set of mutations halved a vaccine’s ability to block transmission, this could vastly increase the number of available hosts in a population. Cobey says it’s hard to imagine that any future gains in infectivity could provide the same boost.
That evolutionary path, towards immune evasion and away from gains in infectivity, is common among established respiratory viruses such as influenza says Adam Kucharski, a mathematical epidemiologist at the London School of Hygiene and Tropical Medicine. “The easiest way for the virus to cause new epidemics is to evade immunity over time. That’s similar to what we see with the seasonal coronaviruses.”
Lab experiments and sequencing of circulating variants have identified a smorgasbord of mutations in the spike protein that weaken the potency of neutralizing antibodies triggered by infection and vaccination. Variants carrying these mutations, such as Beta, have blunted the effectiveness of vaccines. But they have not obliterated the protection that the shots offer, particularly against severe disease.
Compared with other variants, Omicron contains many more of these mutations, particularly in the region of spike that recognizes host cells. Preliminary analysis from Bloom suggests that these mutations might render some portions of spike unrecognizable to the antibodies raised by vaccines and previous infection with other strains. But lab experiments and epidemiological studies will be needed to fully appreciate the effects of these mutations.
Evolving to evade immune responses such as antibodies could also carry some evolutionary costs. A spike mutation that dodges antibodies might reduce the virus’s ability to recognize and bind to host cells. The receptor-binding region of spike — the major target for neutralizing antibodies — is relatively small, says Jason McLellan, a structural biologist at the University of Texas at Austin, and the region might be able to tolerate only so much change and still perform its main job of attaching itself to host cells’ ACE2 receptors.
It’s also possible that repeated exposure to different versions of spike — through infection with different virus strains, vaccine updates or both — could eventually build up a wall of immunity that SARS-CoV-2 will have difficulty overcoming. Mutations that overcome some people’s antibody responses are unlikely to foil responses across an entire population, and T-cell-mediated immunity, another arm of the immune response, seems to be more resilient to changes in the viral genome.
Such constraints might slow SARS-CoV-2’s evasion of immunity, but they are unlikely to stop it, says Bloom. There is clear evidence that some antibody-dodging mutations do not carry large evolutionary costs, says McLellan. “The virus will always be able to mutate parts of the spike.”
A virus in transition
How SARS-CoV-2 evolves in response to immunity has implications for its transition to an endemic virus. There wouldn’t be a steady baseline level of infections, says Kucharski. “A lot of people have a flat horizontal line in their head, which is not what endemic infections do.” Instead, the virus is likely to cause outbreaks and epidemics of varying size, like influenza and most other common respiratory infections do.
To predict what these outbreaks will look like, scientists are investigating how quickly a population becomes newly susceptible to infection, says Kucharski, and whether that happens mostly though viral evolution, waning immune responses, or the birth of new children without immunity to the virus. “My feeling is that small changes that open up a certain fraction of the previously exposed population to reinfection may be the most likely evolutionary trajectory,” says Rambaut.
The most hopeful — but probably least likely — future for SARS-CoV-2 would be to follow the path of measles. Infection or vaccination provides lifetime protection, and the virus circulates largely on the basis of new births. “Even a virus like measles, which has essentially no ability to evolve to evade immunity, is still around,” says Bloom.
A more likely, but still relatively hopeful, parallel for SARS-CoV-2 is a pathogen called respiratory syncytial virus (RSV). Most people get infected in their first two years of life. RSV is a leading cause of hospitalization of infants, but most childhood cases are mild. Waning immunity and viral evolution together allow new strains of RSV to sweep across the planet each year, infecting adults in large numbers, but with mild symptoms thanks to childhood exposure. If SARS-CoV-2 follows this path — aided by vaccines that provide strong protection against severe disease — “it becomes essentially a virus of kids,” says Rambaut.
Influenza offers another scenario — in fact two. The influenza A virus, which drives global seasonal influenza epidemics each year, is characterized by the rapid evolution and spread of new variants able to escape the immunity elicited by past strains. The result is seasonal epidemics, propelled largely by spread in adults, who can still develop severe symptoms. Flu jabs reduce disease severity and slow transmission, but influenza A’s fast evolution means the vaccines aren’t always well matched to circulating strains.
But if SARS-CoV-2 evolves to evade immunity more sluggishly, it might come to resemble influenza B. That virus’s slower rate of change, compared with influenza A, means that its transmission is driven largely by infections in children, who have less immunity than adults.
How quickly SARS-CoV-2 evolves in response to immunity will also determine whether — and how often — vaccines need to be updated. The current offerings will probably need to be updated at some point, says Bedford. In a preprint5 published in September, his team found signs that SARS-CoV-2 was evolving much faster than seasonal coronaviruses and even outpacing influenza A, whose major circulating form is called H3N2. Bedford expects SARS-CoV-2 to eventually slow down to a steadier state of change. “Whether it’s H3N2-like, where you need to update the vaccine every year or two, or where you need to update the vaccine every five years, or if it’s something worse, I don’t quite know,” he says.
Although other respiratory viruses, including seasonal coronaviruses such as 229E, offer several potential futures for SARS-CoV-2, the virus may go in a different direction entirely, say Rambaut and others. The sky-high circulation of the Delta variant and the rise of Omicron — aided by inequitable vaccine roll-outs to lower-income countries and minimal control measures in some wealthy countries such as the United States and the United Kingdom — offer fertile ground for SARS-CoV-2 to take additional surprising evolutionary leaps.
For instance, a document prepared by a UK government science advisory group in July raised the possibility that SARS-CoV-2 could become more severe or evade current vaccines by recombining with other coronaviruses. Continued circulation in animal reservoirs, such as mink or white-tailed deer, brings more potential for surprising changes, such as immune escape or heightened severity.
It may be that the future of SARS-CoV-2 is still in human hands. Vaccinating as many people as possible, while the jabs are still highly effective, could stop the virus from unlocking changes that drive a new wave. “There may be multiple directions that the virus can go in,” Rambaut says, “and the virus hasn’t committed.”
Most Who Took COVID Vax will be dead by the year 2025.
Most of the people who took a COVID “vaccine” will be dead by the year 2025. The proof is now available for all to see.
Thanks to the people who participated in this first ever human experiment with a mRNA gene-therapy, fooled into thinking it was a “vaccine” for a phony “pandemic” allegedly caused by the never-isolated “COVID-19,” we now know the following based on fact-based, post-vaccine research:
1.) It’s not a vaccine. The COVID-19 mRNA vaccine does not provide immunity to Covid or it’s variants so you can still catch Covid and transmit it to others making you asymptomatic. You will likely need a booster shot every 6 months, so get ready to roll up that sleeve every six months once that system rolls out.
[link to www.bustle.com]
2.) The 95% efficacy is the RRR (Relative Reduction Risk) where the real reduction rate ARR (Absolute Reduction Risk) is less than 2% as per this scientific Lancet study.
[link to www.thelancet.com]
This means you are really not protected much at all, as the architects of this phony pandemic would like you to ‘believe.’
3.) The lipid nanoparticles in the vaccines do not remain in the intramuscular region of the deltoid muscle. They seep out into the cardiovascular system infecting the entire body with spike-protein. Something the manufacturers claimed would never happen, yet it does and is why the adverse-side effects are so bad with this shot.
[link to www.sciencedirect.com]
4.) The spike-protein itself is toxic and a part of the disease pathology being the cause of inflammation, ACE2 deregulation and opens up immunity pathways. This means Myocarditis (heart inflammation), Encephalitis (brain inflammation ) and hepatomegaly (liver inflammation) are huge risks and confirmed by many adverse-reactions reported to VAERS and EuroVigilance.
This means the spike-protein itself is enough to damage the cardiovascular system and organs, some of which can have harmful events in the future and is like injecting someone with Covid-19 damaging the inside of the body rather than the lungs.
5.) The synthetic spike-protein itself has coding errors and a 5 GxxxG motif placing it in the category of a prion which could pose a long-term risk of neural degenerative diseases.
6.) The lipid nanoparticles after injection bulk in Ovaries in women followed by bone-marrow. Dr. Robert Malone the inventor of mRNA covers these findings in lay terms for stupid people who can’t process scientific data easily.
[link to www.bitchute.com]
Hal Turner Editorial Opinion
If it wasn’t for the highly uninformed and unaware folks who jumped on an experimental gene-therapy shot which skipped any real, meaningful, trials that would have presented the above findings, we now have this data and evidence from the human lab-rats running around gleefully and ignorantly celebrating their Eugenics shot, completely blind to the short-term and long term consequences that this data all points to: MOST of them will die from one or more of the conditions outlined in the reports above, and MOST of those deaths will take place by the year 2025.
Enjoy your harmful spike-protein that you will never get out of your body, and the neural degenerative, long-term risks, which ultimately could lead to untreatable deadly neurological illnesses as your brain slowly rots and deteriorates from the prion causing misfolded proteins that damage your neurons slowly over time.
Your sacrifice for the safety of others, which will likely kill most of you, was based on your ignorance, your failure to research things for yourself, and your willingness to simply accept what other (ignorant) people – like politicians – told you.
World population of 500 million coming; just as the Georgia Guide Stones suggested, and the psychotic maniacs who believe humans need to be culled from the planet, took literally.
How about we blame the real culprits who created this in the first place:
Fauci with his gain-of-function research that was banned in the US so he moved it the lab in Wuhan where this took place.
Bill Gates with his depopulation agenda and ties to pedophile Jeffery Epstein.
The CDC/WHO/Rockefeller Foundation and John Hopkins, who ran Event 201, Spars, Lockstep, planning all of this for their globalist new world order.
COVID-19 variants will keep coming until everyone can access vaccines
The emergence of Omicron underscores the consequences of vaccine inequity. Experts say it will take more than donations to fix the problem.
Angelique Coetzee was puzzled. The South African doctor had been seeing COVID-19 patients who mostly had sore throats and fevers. But on November 18 Coetzee examined a 29-year-old man complaining of extreme fatigue and severe headaches—symptoms more in line with heat stroke than COVID-19. By the end of the day, Coetzee had treated seven or eight similar cases.
“It didn’t make any sense to me,” says Coetzee, chair of the South African Medical Association.
Within a week, researchers determined that the patients were infected with a new SARS-CoV-2 variant, now known as Omicron, that has a large number of mutations and can spread more rapidly than previous variants. Omicron is now dominant in South Africa and many other countries, including the United States.
Omicron’s rise has reignited discussion about how to ensure the entire world can get a jab. The World Health Organization has set a target of vaccinating 70 percent of the global population by mid-2022. But while wealthy countries like the U.S. have already immunized more than 60 percent of their populations, vaccination in low-income countries is lagging. In South Africa only 27 percent of the population is fully vaccinated, while in Nigeria, Papua New Guinea, and Sudan that number is less than 3 percent.
The problem goes beyond supply constraints. Experts say low-income countries face massive infrastructure challenges to distribute doses quickly and widely. They argue that wealthy countries have more than just a moral obligation to help address vaccine equity, because when the virus is circulating anywhere, it has more opportunities to mutate and spread.
Mutations are normal for a virus, whose only purpose is to infect cells and replicate inside of them. In a single person’s body, the SARS-CoV-2 virus might copy its own genome at least thousands of times. Coronaviruses have so-called proofreading enzymes to keep them from introducing mistakes into their genetic code, but errors are bound to slip through, and that’s when mutations occur.
Most of these mutations are useless or even destructive to the virus, points out Wendy Barclay, a virologist at Imperial College London. She says the chance that a mutation will give an advantage to the virus, such as making it more transmissible or able to evade immunity from vaccination, is as low as 1-in-100,000. But those odds increase the more a virus is allowed to replicate.
The best way to keep new variants from arising is thus to deny the virus the opportunity to spread and replicate. That can be done by social distancing, wearing masks, and testing—but the best weapon is widespread vaccination.
“As long as Africa is not vaccinated, you will never be able to sleep soundly,” Coetzee says.
How vaccination suppresses variants
Vaccines have two main advantages: They save lives by preventing people from getting severely sick, and they help control viral replication. Breakthrough infections in vaccinated people tend to be mild, which means a sick person won’t exhale as much virus for as long as they would if they were unvaccinated. That gives the virus less time to replicate inside the body and fewer opportunities to multiply in the rest of the population.
That’s where vaccine equity comes in. Allowing a virus as transmissible as SARS-CoV-2 to run through parts of the world where large swaths of people are unvaccinated creates a real problem, says Ingrid Katz, associate faculty director at the Harvard Global Health Institute. “The only way to get in front of it is to use everything in your arsenal, and that includes vaccinating the world,” she says.
Although it’s nearly impossible to pinpoint the exact origins of a viral variant, we do know that in India, low levels of vaccination played a role in the catastrophic emergence and surge of the Delta variant earlier this year.
In early 2021 the country had begun rolling out vaccines only to those at high risk of severe disease due to their age, comorbidities, or frequent exposure to the virus. The rest of the adult population wasn’t scheduled for shots until September 2021.
“All this was based on premise that India was out of the danger zone,” says K. Srinath Reddy, president of the Public Health Foundation of India. Cases and deaths were low in mid-January, and experts were predicting that India had built up enough herd immunity to avoid another wave. Then, Reddy says, India saw a surge of travel, election rallies, and religious festivals.
“It was as though India had turned its back on the virus, though the virus had not turned its back on us,” he says.
The Delta variant was first identified in March, when less than one percent of the population of nearly 1.4 billion people was fully vaccinated. Sure enough, cases and hospitalizations surged—soon followed by a staggering loss of life.
A shaky start to vaccine supplies
Unfortunately, vaccine inequities began to build long before any COVID-19 vaccines were even approved. Wealthy countries pre-ordered hundreds of billions of doses in early deals with pharmaceutical companies—leaving low-income countries without access to the vaccines from the start.
“You set up a system of inequity right from the get-go,” Katz says.
The WHO partnered with international nonprofits to address those inequities through COVAX, an initiative to secure doses for low-income countries. But vaccines are still disproportionately going to wealthy countries as they administer booster doses.
Some countries have stepped up their donations in the name of vaccine equity, but Reddy points out that these donations have not always been well thought out. In the last year, there have been several high-profile instances in which wealthy countries waited to share their vaccine stockpiles until they were close to expiring—causing hundreds of thousands of donated doses to go to waste. For instance, South Sudan had to destroy nearly 60,000 doses in April, and up to a million doses went to waste in Nigeria in November.
“That’s not charity—that’s just dumping,” Reddy says.
Still, Amavi argues that COVAX has made an extraordinary difference in addressing vaccine equity for COVID-19 compared to past vaccination campaigns. The human papillomavirus vaccine, for example, first became available in 2006—but many African countries have only had access to it in the last couple of years.
“With COVAX we have seen that in less than one year, all COVID-19 vaccines have been made available everywhere,” Amavi says. “I think it is a great achievement to have bridged the gap between producing countries and African countries that were not receiving the vaccine in the beginning.”
The rocky road to global distribution
Once countries have secured enough doses, though, they must figure out how to distribute them. And although low-income countries might get discounts on the jabs, it costs them more than high-income countries to roll out the shots.
“It’s a challenge in Africa,” Coetzee says. “It doesn’t matter how many donations you give us.”
According to the Global Dashboard for Vaccine Equity, low-income countries would have to increase their healthcare spending by an average of nearly 57 percent to vaccinate 70 percent of their populations. That’s because many low-income countries lack the infrastructure—from electrical grid capacity to a trained healthcare workforce—to rapidly administer doses to billions of people. Distributing the mRNA vaccines is particularly daunting since they require access to cooler trucks and ultra-cold storage at healthcare facilities that are under-resourced even in the best of times.
By contrast, high-income countries only need to increase spending by less than an additional one percent to vaccinate their entire populations.
In India, the arrival of the Delta variant prompted the country to step up immunizations. Reddy says that the country has used drones to help get doses into remote areas and has launched a door-to-door vaccination campaign. India’s health minister reports that 85 percent of its eligible population has now had a first dose and more than half is fully vaccinated. However, many low-income countries simply lack the capacity to mobilize thousands of healthcare workers to go door-to-door—if they have that many trained professionals at all.
Yet another challenge is convincing people to take the vaccine. Amavi says much of the vaccine hesitancy across the world can be blamed on a COVID-19 infodemic—or the spread of misinformation and disinformation that has been sowed by the anti-vax movement.
But Katz says people in low-income countries are also understandably skeptical. She points to early reports that the Pfizer and Moderna vaccines were safer and more efficacious than those available to low-income countries, such as AstraZeneca and Johnson & Johnson.
Although this imbalance was because of cold-chain issues, Katz says it created some understandable vaccine hesitancy in countries where people feel they have gotten stuck with the worse vaccines. To remedy this, she says, public health experts must do better to reassure the population that the vaccines they’re receiving are safe and effective.
What can be done about inequities?
Solutions to vaccine inequities start at the country level. Katz says that wealthy countries can share more of their stockpiled vaccine doses or even forgo their place in line for upcoming shipments. The international community can also provide financial assistance for low-income countries to build up healthcare infrastructure—which would also help during the inevitable next pandemic.
Public health experts have also called on Moderna and Pfizer to help low-income countries produce their own mRNA vaccines—which would dramatically reduce the burdens of acquiring, transporting, and distributing them. Katz says this would require the companies not just to release their intellectual property rights but also to share their technology and raw materials.
She adds that although the Pfizer and Moderna vaccines stood out early on—proving to be more than 90 percent effective at preventing severe disease—there is promising new evidence for other vaccines.
The one-dose Johnson & Johnson vaccine, for example, was only 66.3 percent effective in its original clinical trials, but the company reported in the fall that a second dose raised the vaccine’s efficacy against moderate to severe disease caused by the original virus to 94 percent. Although the J&J shot may be less effective against newer variants, Katz argues that this data shows two doses of the jab are about as effective as the mRNA vaccines.
Barclay, too, points to new data out of the United Kingdom showing that mixing vaccines can boost immunity. A study published in The Lancet found that people who initially received two doses of the AstraZeneca vaccine had higher levels of immunity after receiving a booster of one of the six other vaccines that are available.
“So all is not lost,” she says. If countries can make progress getting the first shots in arms, they can always come back and boost with the mRNA vaccines.
Coetzee, meanwhile, advocates for developing vaccine tablets that can be administered more easily in low-income countries. Even if the mRNA vaccines could be made widely available in low-income countries, they would still need cooler trucks to transport it and enough trained medical personnel to mix the vaccine, dilute it, portion it out into a syringe, and administer doses.
“Everything can potentially lead to an error,” she says. “To give a tablet, there’s not a lot that can go wrong. You just need to make sure that the patient swallows the tablet.”
Ultimately, most experts agree that policymakers and voters everywhere need to understand that their safety is ephemeral until more of the world is vaccinated. Katz urges people to make donations, advocate within their communities, and petition their governments to do more to address vaccine equity.
“When will we learn that we have to be in collaboration globally?” she says. “We cannot go on like this.”
Coetzee agrees. She suggests that richer countries launch programs to allow their citizens to sponsor vaccines for people in low-income countries. Beyond that, she says, everyone who has access to shots can help simply by getting vaccinated, getting boosted if you’re eligible, masking up, and practicing social distancing and hand washing.
“What are you doing as a responsible citizen?” she asks. “You also need to play a role.”
Omicron’s feeble attack on the lungs could make it less dangerous
Mounting evidence from animal studies suggests that Omicron does not multiply readily in lung tissue, which can be badly damaged in people infected with other variants
Early indications from South Africa and the United Kingdom signal that the fast-spreading Omicron variant of the coronavirus SARS-CoV-2 is less dangerous than its predecessor Delta. Now, a series of laboratory studies offers a tantalizing explanation for the difference: Omicron does not infect cells deep in the lung as readily as it does those in the upper airways.
“It’s a very attractive observation that might explain what we see in patients,” says Melanie Ott, a virologist at the Gladstone Institute of Virology in San Francisco, California, who was not involved in the research. But she adds that Omicron’s hyper-transmissibility means that hospitals are filling quickly — despite any decrease in the severity of the disease it causes.
Authorities in South Africa announced on 30 December that the country had passed its Omicron peak without a major spike in deaths. And a 31 December UK government report said that people in England who were infected with Omicron were about half as likely to require hospitalization or emergency care as were those infected with Delta.
But the number of people who have gained immune protection against COVID-19 through vaccination, infection or both has grown over time, making it difficult to determine whether Omicron intrinsically causes milder disease than earlier variants. For answers, researchers have turned to animals and to cells in laboratory dishes.How the coronavirus infects cells — and why Delta is so dangerous
Michael Diamond, a virologist at Washington University in St. Louis, Missouri, and his colleagues infected hamsters and mice with Omicron and other variants to track disease progression. The differences were staggering: after a few days, the concentration of virus in the lungs of animals infected with Omicron was at least ten times lower than that in rodents infected with other variants. Other teams have also noted that compared with previous variants, Omicron is found at reduced levels in lung tissue.
Diamond says he was especially shocked to see that the Omicron-infected animals nearly maintained their body weight, whereas the others quickly lost weight — a sign that their infections were causing severe disease. “Every strain of SARS-CoV-2 has infected hamsters very easily, to high levels,” he says, “and it’s clear that this one is different for hamsters.” The lungs are where the coronavirus does much of its damage, and lung infection can set off an inflammatory immune response that ravages infected and uninfected cells alike, leading to tissue scarring and oxygen deprivation. Fewer infected lung cells could mean milder illness.
Another group found that Omicron is much less successful than previous variants at infecting lung cells and miniature lung models called organoids4. These experiments also identified a plausible player in the difference: a protein called TMPRSS2, which protrudes from the surfaces of many cells in the lungs and other organs, but is notably absent from the surfaces of most nose and throat cells.
Previous variants have exploited this protein to infect cells, but the researchers noticed that Omicron doesn’t bind to TMPRSS2 so well. Instead, it tends to enter cells when it is ingested by them.
Upper airway preferred
Difficulty entering lung cells could help to explain why Omicron does better in the upper airways than in the lungs, says Ravindra Gupta, a virologist at the University of Cambridge, UK, who co-authored one of the TMPRSS2 studies4. This theory could also explain why, by some estimates, Omicron is nearly as transmissible as measles, which is the benchmark for high transmissibility, says Diamond. If the variant lingers in the upper airways, viral particles might find it easy to hitch a ride on material expelled from the nose and mouth, allowing the virus to find new hosts, says Gupta. Other data provide direct evidence that Omicron replicates more readily in the upper airways than in the lungs.
The latest results could mean that “the virus establishes a very local infection in the upper airways and has less chance to go and wreak havoc in the lungs”, Ott says. That would be welcome news — but a host’s immune response plays an important part in disease severity, and scientists need more clinical data if they are to understand how Omicron’s basic biology influences its disease progression in humans.
Omicron’s course of infection could also have implications for children, says Audrey John, a specialist in paediatric infectious disease at the Children’s Hospital of Philadelphia in Pennsylvania. Young children have relatively small nasal passages, and babies breathe only through their noses. Such factors can make upper respiratory conditions more serious for children than for adults, John says. But she adds that she has not seen data suggesting an uptick in the numbers of young children hospitalized for croup and other conditions that could indicate a severe infection of the upper respiratory tract.
Although there is still much to learn about the new variant, Gupta says that fears raised in late November by the multitude of mutations in Omicron’s genome have not been completely borne out. He says the initial alarm offers a cautionary tale: it’s difficult to predict how a virus will infect organisms from its genetic sequence alone.
The Omicron Variant: Mother Nature’s COVID-19 Vaccine?
For several weeks, much of the world has been obsessed with the Omicron variant of the virus that causes COVID-19. What initially started as a trickle of media reports about a highly-mutated and rapidly-spreading “variant of concern” that originated in Africa quickly transformed into a global hysteria that once again closed borders, disrupted global stock markets, switched countless schools and universities to virtual learning, triggered broadening of vaccination and booster mandates, and persuaded some officials in the United States government to predict a “winter of death” and caution families not to gather over the sacred holiday period. Is this fear and isolation truly warranted?
This panic has been fueled solely by rising COVID case counts (some of which could be attributed to increased testing) coupled with the government’s and mainstream media’s addiction to fostering fear and hysteria. As both a physician and scientist, I believe it is essential that we take a measured, evidence-based approach to dealing with Omicron. And when we look at the totality of the emerging facts, there is a very real possibility that Omicron could lead us into light instead of darkness. Here’s why:
To understand why the Omicron variant could be a blessing in disguise — and possibly usher in the end of the COVID-19 pandemic by acting as Mother Nature’s vaccine — we must examine what makes this virus unique. The Omicron variant has over 26 mutations in its RNA sequence, which is a tremendous number of changes in the genetic sequence of the virus. Among these many mutations is an “insertion” where a new letter is inserted into the gene sequence. Interestingly, this sequence resembles that of another coronavirus, which causes the common cold. The Omicron variant may have picked up genetic sequences from a common cold coronavirus in someone who was infected with both viruses and, in doing so, become weakened.
Because of the enormous number of mutations, the Omicron variant is in many ways a totally new virus. It appears that it has become more transmissible (doubling in just 1-2 days), in part due to its ability to evade immunity, while becoming a lot less deadly. While the case numbers have spiked, data from South Africa and the UK have suggested that the chance of becoming very sick or dying has plummeted by 80% or higher.
Why is this so important? Because viruses compete with one another, and the Omicron variant is rapidly replacing the more dangerous Delta variant. Soon, it could become the only COVID virus around, causing no more than a bad cold in most people, particularly the vaccinated. And as it rapidly spreads throughout this holiday season as we all travel and congregate — even with vaccinations and masks — the Omicron variant is effectively giving every person it touches a type of immunity that no COVID vaccine has yet given us: a robust, possibly long-acting immunity against the entire virus, rather than just the spike protein. We know from many other vaccines that exposing the body to a weakened or attenuated version of a live virus can produce the most effective protection. Anyone who has been vaccinated against measles, mumps, rubella, rotavirus, chickenpox, smallpox, or yellow fever has actually been injected with a live, attenuated version of the very same virus that causes disease.
So, if the Omicron variant acts like a live, attenuated COVID vaccine that rapidly spreads in the air, rather than through a needle, we might very well emerge from this holiday season finally facing an end to the deadly phase of pandemic. And if you add to this the widespread availability of vaccinations for those at risk and two newly FDA-approved oral treatments for COVID-19 that can reduce hospitalization by yet another 80%, there is indeed a very bright light at the end of this long and dark tunnel. Let’s look forward to 2022 with hope and view it as an opportunity to heal, rebuild, and move on.
Is Omicron really less severe than Delta? Here’s what the science says.
This variant is more transmissible. So how do you protect yourself? And what are the implications for vaccines, masks, hygiene, and social distancing?
If you get COVID-19 in the United States right now, chances are high that it’s the Omicron variant, which now accounts for around 95 percent of the country’s reported cases. With dozens of mutations, Omicron is different from the previously dominant Delta variant in significant ways, which means that, after two years of getting a handle on how to manage risk, you might need to shift at least some of your behaviors.
Among the changes, Omicron is more transmissible and better at evading existing antibodies. “To me, the biggest shift, the most shocking thing, is how incredibly infectious this thing is. I have never seen anything so infectious in my life,” says Carlos del Rio, an epidemiologist and infectious diseases specialist Emory University in Atlanta, Georgia. At the same time, Omicron causes different symptoms and seems to lead to less severe disease.
Still, different strains of SARS-CoV-2 share important similarities, and much of the basic public health advice—get vaccinated, wear a mask—remains the same. Here’s what the latest research says about staying safe in the age of Omicron.
Is Omicron really causing less severe disease than Delta?
Multiple lines of evidence from various parts of the world suggest that the Omicron variant causes a less severe form of COVID-19. In South Africa, where Omicron was first detected in November 2021, a private health insurance administrator reported in mid-December that adults with Omicron were 29 percent less likely to be hospitalized, compared with adults infected several months earlier. In the U.K., the rate of hospital admission among people who went to the emergency room with Omicron was a third of what it was for Delta, according to a summary of research from the U.K. Health Security Agency released on December 31, 2021.
As of early January, U.S. adults with Omicron were less than half as likely to visit the emergency room, be hospitalized, or be put on a ventilator, according to preliminary work by researchers from Case Western Reserve University School of Medicine. Their study, which has not yet been peer-reviewed, examines data for more than 14,000 patients and accounts for their vaccination status and any pre-existing conditions.
A shift in symptoms reflects those trends, del Rio says. In the hospital, patients are showing up less often with pneumonia-like symptoms and hyperactive immune systems, as seen in previous waves. Instead, they’re more often presenting with congestion and scratchy throats. “In Omicron, the symptoms are more like a head cold,” he says.
Does severity differ based on age or preexisting conditions?
Omicron appears to be less severe than Delta in all age groups, even in adults older than 65 and in children too young to be vaccinated, according to the Case Western study. Still, as with other health issues, age remains a factor, del Rio says. “For any disease, if you’re older, you’re going to do a lot worse,” he says.
People with underlying conditions or compromised immune systems also remain more vulnerable, as do people who are unvaccinated. Although current vaccines are less effective at preventing symptoms from Omicron than from Delta, the U.K. report found that people who were fully boosted were up to 88 percent less likely to be hospitalized with Omicron compared with unvaccinated people. Hospitals around the country report that unvaccinated patients make up the majority of people now in intensive care units.
Regardless of age or health status, people infected with Omicron can feel terrible even if they don’t have to go to the hospital, and the variant continues to hospitalize and kill many people, emphasized Tedros Adhanom Ghebreyesus, director-general of the World Health Organization, in a virtual press conference last week.
Why is Omicron dangerous if it’s less severe than Delta?
Omicron is between two and four times more contagious than Delta, according to a Danish study that has not yet been peer reviewed. It’s also better at evading the antibodies triggered by vaccines, which is why it’s causing more breakthrough infections. As a result, more people are getting sick and showing up at hospitals, where more staff are calling in sick, del Rio says.
Omicron has 36 mutations within its spike protein, which is the part essential for anchoring the virus on human cells and infecting them. Though none are peer reviewed, at least half a dozen studies using small animal models—such as mice and hamsters—and laboratory cell cultures have started to reveal how those mutations alter the way that Omicron enters cells and replicates, says John Moore, a vaccine researcher and virologist at Weill Cornell Medicine in New York.
Unlike previous variants, Omicron appears unable to infect lung cells as efficiently, which in turn makes it less damaging and the symptoms less severe. Viral loads are significantly lower in the lungs of Omicron-infected rodents in some studies. But in the upper respiratory tract, which includes the nose and sinuses, Omicron seems to replicate more than a hundred times faster than Delta.
That mix of changes—the preference for the upper airway, better immune invasion, and high transmissibility—reflects how evolution pushes the virus to ensure its own future by replicating and spreading even when that does not make individuals sicker.
“It kind of doesn’t matter to the virus, once it’s replicated, whether that person lives or dies as long as it can get to the next host,” Moore says. “It’s all about genome replication.”
What do these changes mean for at-home testing?
All strains of the SARS-CoV-2 virus can infect cells in the mouth, and Omicron may be particularly abundant there compared with other variants, early evidence suggests. In one study that has not yet been peer reviewed, researchers in South Africa tested 382 people who were not sick enough to be hospitalized but still had COVID-19 symptoms. They found that in those with Delta, nose swabs were more accurate, but for Omicron, saliva tests worked best.
Other studies also suggest that rapid antigen tests that rely on nasal swabs might be especially slow to identify infections with Omicron. In one study posted last week that has not yet been peer reviewed, researchers looked at samples from 30 people who tested positive for COVID-19 around the United States during outbreaks in early December. For most cases of Omicron, PCR tests showed positive days before a rapid test did. Those results echo what people have been reporting on social media, says study coauthor Anne Wyllie, a medical microbiologist at the Yale School of Public Health in New Haven, Connecticut.
Given the growing evidence for Omicron’s prevalence in spit, social media has been full of DIYers and researchers advocating that people swab their throats with at-home test kits. Wyllie has even tried it herself using the swab from a rapid test. The result was negative, but she felt more confident that it was a true negative than if she’d only swabbed her nose.
“It’s not what’s been authorized by the FDA, and it’s a very tricky topic to speak out on because of that,” she says. That’s why many other experts are hesitant to recommend the off-label use. While throat swabs might eventually become part of the testing equation, rapid tests were designed for noses, not throats, says Jill Weatherhead, an infectious disease expert at the Baylor College of Medicine in Houston.
“At this point, the recommendation would be to continue to do the test as they’ve been designed to be done until further testing has been shown that it’s effective,” Weatherhead says.
Does double masking help protect against Omicron?
The Centers for Disease Control and Prevention does not currently recommend double masking or the use of specific masks. But other countries, including Austria, France, and Germany, have upgraded their guidelines to recommend medical-grade varieties, such as surgical masks or N95s. And some U.S. experts have spoken out in favor of higher quality masks.
One study found that, if fitted correctly, N95s block an average of 90 percent of exhaled particles, while surgical masks blocked 74 percent. That can make a substantial difference in community spread. In Bangladesh, an intervention boosted the percentage of people wearing surgical masks in some villages from 13 percent to 42 percent. Researchers then found an 11 percent drop in COVID-19 symptoms, with bigger gains in older groups. Evidence on cloth masks is mixed, but wearing a cloth mask over a surgical mask can block more than 85 percent of cough particles, according to some research.
Experts recommend choosing your mask based on the situation you’re in. In social situations, Moore wears a cloth mask decorated with the logo of his favorite soccer team, Liverpool. When walking around at work or in stores, he wears a thicker cloth mask that he finds comfortable. Del Rio says he wears an N95 whenever he’s with patients. But masking alone won’t protect you from Omicron, he adds. “This is not about some magic bullet, this is about a combination effect,” he says. “If you’re vaccinated and you’re boosted and you’re wearing a good-fitting mask, you can spend a lot of time with somebody.”
Do we still need to disinfect surfaces, stand further away from each other, or alter any other aspect of personal hygiene?
Like prior variants, Omicron is primarily airborne, and experts agree that wiping down surfaces is probably more trouble than it’s worth. “Transmission from surfaces is low,” Wyllie says. Given “the time, energy, money, resources and mental health put into that kind of concern—you’re better spending that on hand-washing, social distancing, and mask-wearing.“
Also, the six-foot rule is more of a reminder that being close to an infected person increases the risk of transmission, says Abraar Karan, an infectious diseases doctor at Stanford University in Palo Alto, California.
“Transmission can happen beyond six feet of distance, for sure,” he says. “However, distance makes transmission less likely, as aerosols get diluted with further distance.” Your risk also depends on ventilation, what kinds of masks people around you are wearing, and other factors.
Is long COVID still a risk when it comes to Omicron?
It’s too soon to know, and it likely will be months before researchers can tell if Omicron causes symptoms that stick around for the long-term. But some experts are hopeful that long lasting consequences will be less common because of Omicron’s tendency to stay out of the lungs, and because more people are getting vaccinated, which can help prevent infections and lower risk of developing a number of symptoms. “I would suspect we will still see cases,” Wyllie says. “But because we have far more people now vaccinated, I am hoping we see less long COVID-19.”
Omicron thwarts some of the world’s most-used COVID vaccines
Inactivated-virus vaccines elicit few, if any, infection-blocking antibodies — but might still protect against severe disease.
The world’s most widely used COVID-19 vaccines provide little to no protection against infection with the rapidly spreading Omicron variant, laboratory evidence suggests.
Inactivated-virus vaccines contain SARS-CoV-2 particles that have been chemically treated to make it impossible for them to cause an infection. Stable and relatively easy to manufacture, such vaccines have been distributed widely as part of China’s global vaccine diplomacy, helping them to become the jab of choice in many countries. But a multitude of experiments show that they are consistently hobbled by Omicron.
Many people who receive two jabs of an inactivated vaccine fail to produce immune molecules that can counter Omicron transmission. And even after a third dose of an inactivated vaccine, an individual’s levels of ‘neutralizing’ antibodies, which provide a potent safeguard against viral infection of cells, tend to remain low. A third shot of another type of vaccine, such as those based on messenger RNA or purified proteins, seems to offer better protection against Omicron.
The findings are prompting many scientists and public-health researchers to re-evaluate the role of inactivated vaccines in the global fight against COVID-19.
“At this stage, we have to evolve our ideas and adjust our vaccination strategies,” says Qiang Pan-Hammarström, a clinical immunologist at the Karolinska Institute in Stockholm.
Inactivated vaccines were instrumental in the campaign for worldwide vaccine coverage last year. They include those made by China’s Sinovac and Sinopharm, which together account for nearly 5 billion of the more than 11 billion COVID-19 vaccine doses delivered globally so far, according to numbers compiled by data-tracking firm Airfinity in London (see ‘Many shields against COVID-19’). More than 200 million doses of other inactivated shots such as India’s Covaxin, Iran’s COVIran Barekat and Kazakhstan’s QazVac have also been delivered.
Such products remain crucial for preventing hospitalization and death from COVID-19. And they can still serve a valuable immune-priming function for as-yet unvaccinated individuals.
But an early sign that inactivated vaccines might not hold up to Omicron came in December, when researchers in Hong Kong analysed blood from 25 recipients of the two-dose CoronaVac vaccine, made by the Beijing-based company Sinovac. Not a single person had detectable neutralizing antibodies against the new variant — raising the possibility that all the participants were highly vulnerable to Omicron infection.
Sinovac has disputed this finding, pointing to internal data showing that 7 out of 20 people who had received the company’s vaccine had tested positive for antibodies capable of neutralizing Omicron. Other studies involving people immunized with Covaxin, which is made by Bharat Biotech in Hyderabad, India, and BBIBP-CorV, produced by state-owned Chinese company Sinopharm, in Beijing, have also concluded that inactivated vaccines retain some potency against Omicron — although, as researchers at the Translational Health Science and Technology Institute in Faridabad, India, put it in their study, the immune responses remain “sub-optimal”. The work on Covaxin has not yet been peer reviewed.
A third dose of inactivated vaccine helps to restore neutralization activity for many individuals. A 292-person study by researchers at the Shanghai Jiao Tong University School of Medicine in China, for example, identified neutralizing antibodies against Omicron in just 8 people tested 8–9 months after an initial course of BBIBP-CorV. After another shot of the same vaccine, that number rose to 228. This work has not yet been peer reviewed. Omicron likely to weaken COVID vaccine protection
Levels of neutralizing antibodies in each person’s blood remained low. But as molecular virologist Rafael Medina at the Pontifical Catholic University of Chile in Santiago points out: “There are other parts of the immune response that are also playing a role.” T cells destroy infected cells; B cells remember past infections and strengthen immune responses for the future; and binding antibodies contribute to viral control.
In a preprint published in December, Medina and his co-authors — led by immunologist Galit Alter at the Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts — showed that people immunized with CoronaVac maintain non-neutralizing antibodies that both bind Omicron and assist immune cells in gobbling up infected cells.
On the defensive
Those kinds of result show that recipients of inactivated vaccines, although not necessarily protected against infection by Omicron, should still be shielded from the worst ravages of COVID-19 triggered by the variant, says Murat Akova, an infectious-disease specialist at Hacettepe University School of Medicine in Ankara.
All the same, an extra dose of vaccine could offer some much-needed immune insurance. Experiments conducted by Pan-Hammarström and her colleagues found that, after two doses of inactivated vaccine, an mRNA top-up hoists levels of binding antibodies, memory B cells and T cells. And studies of samples from China, and the United Arab Emirates have shown that a protein-based booster triggers higher numbers of neutralizing antibodies than does a third shot of an inactivated vaccine. Many of these results have not yet been peer reviewed.
But a single booster with a different type of vaccine might not be enough to subdue Omicron, warns Akiko Iwasaki, a viral immunologist at Yale School of Medicine in New Haven, Connecticut.
Iwasaki and her co-authors studied blood samples from 101 individuals who received two doses of CoronaVac followed by an mRNA booster. Before the boost, the samples showed no detectable Omicron neutralization. Afterwards, 80% of analysed samples showed some Omicron-blocking activity. But the quantities of antibodies that had Omicron-neutralizing potential were not much greater in this group than in a separate population that had received two doses of mRNA vaccine and no booster. The work has not yet been peer reviewed.
Before the Omicron variant emerged, Iwasaki had been advocating single mRNA boosters for recipients of inactivated vaccines. “We were really celebrating how wonderful this strategy is,” she says, “and then — boom! — Omicron hit.” Now, she thinks these people probably need two extra jabs.
“The bar keeps being raised by the variants,” Iwasaki says. “We’re playing catch up all the time.”
Deltacron: the story of the variant that wasn’t
News of a ‘super variant’ combining Delta and Omicron spread rapidly last week, but researchers say it never existed and the sequences may have resulted from contamination.
On 7 January, virologist Leondios Kostrikis announced on local television that his research group at the University of Cyprus in Nicosia had identified several SARS-CoV-2 genomes that featured elements of both the Delta and Omicron variants.
Named by them as ‘Deltacron,’ Kostrikis and his team uploaded 25 of the sequences to the popular public repository GISAID that evening, and another 27 a few days later. On 8 January, financial news outlet Bloomberg picked up the story, and Deltacron became international news.
The response from the scientific community was swift. Many specialists declared both on social media and to the press that the 52 sequences did not point to a new variant, and were not the result of recombination — the genetic sharing of information — between viruses, but instead probably resulted from contamination in the laboratory.
“There is no such thing as #Deltacron,” tweeted Krutika Kuppalli, a member of the World Health Organization’s COVID-19 technical team based at the Medical University of South Carolina in Charleston, on 9 January. “#Omicron and #Delta did NOT form a super variant.”
Spread of misinformation
The story behind how a small crop of SARS-CoV-2 sequences became the focus of a brief and intense scientific controversy is complicated. And although some researchers applaud the system for quickly catching a possible sequencing error, others warn that the events of last week may offer a cautionary tale on the spread of misinformation during the pandemic.
Kostrikis says that aspects of his original hypothesis have been misconstrued, and that — despite the confusing name that some of the media took to mean that the sequences were those of a Delta–Omicron recombinant virus — he never said that the sequences represented a hybrid of the two.
Nevertheless, 72 hours after the researchers uploaded the sequences, Kostrikis removed them from public view on the database, pending further investigation.
Cheryl Bennett, an official at the GISAID Foundation’s Washington DC office says that, as more than 7 million SARS-CoV-2 genomes have been uploaded to the GISAID database since January 2020, some sequencing mistakes should not come as a surprise.
“However, rushing to conclusions on data that have just been made available by labs that find themselves under significant time pressure to generate data in a timely manner is not helpful in any outbreak,” she says.
An error in the sequence?
The ‘Deltacron’ sequences were generated from virus samples obtained by Kostrikis and his team in December as part of an effort to track the spread of SARS-CoV-2 variants in Cyprus. While examining some of their sequences, the researchers noticed an Omicron-like genetic signature in the gene for the spike protein, which helps the virus to enter cells.
In an e-mail to Nature, Kostrikis explains that his initial hypothesis was that some Delta virus particles had independently evolved mutations in the spike gene similar to those common in Omicron. But after the wide news coverage, other scientists working on genetic sequencing and COVID-19 pointed out another possibility: a lab error.
Sequencing any genome depends on primers — short bits of manufactured DNA that serve as the starting point for sequencing by binding to the target sequence.
Delta, however, has a mutation in the spike gene that reduces some primers’ ability to bind to it, making it harder to sequence this region of the genome. Omicron doesn’t share this mutation, so if any Omicron particles were mixed into the sample owing to contamination, it might make the sequenced spike gene seem to be similar to that in Omicron, says Jeremy Kamil, a virologist at Louisiana State University Health Shreveport.
This type of contamination, says Kamil, is “so, so common”.
Kostrikis counters that if Deltacron was a product of contamination, sequencing should have turned up Omicron sequences with Delta-like mutations, as Omicron has its own primer-hindering mutation. He adds that the Deltacron lab contamination argument was “spearheaded by social media without considering our complete data, and without providing any real solid evidence that it is not real.”
However, other researchers have also pointed out that even if the sequences aren’t the result of contamination, the mutations identified by Kostrikis are not exclusive to Omicron and are found in other variants, making ‘Deltacron’ something of a misnomer.
In fact, GISAID is littered with sequences that have elements of sequences seen in other variants, says Thomas Peacock, a virologist at Imperial College London. Such sequences “get uploaded all the time”, he says. “But, generally, people don’t have to debunk them because there isn’t a load of international press all over them.”
“Scientists need to be very careful about what they are saying,” one virologist, who wanted to remain anonymous to avoid becoming embroiled in the controversy, told Nature. “When we say something, borders can be closed.”
Kostrikis now says he is “in the process of investigating all the crucial views expressed by prominent scientists around the world about my recent announcement”. He says he plans on submitting the research for peer review.
In the interim, Kamil and other researchers fear that such incidents could make researchers more hesitant to share time-sensitive data. “You have to allow for the scientific community to self-correct,” he says. “And, in a pandemic, you have to facilitate the rapid sharing of viral genome data, because that’s how we find variants.”
Where did Omicron come from? Three key theories
The highly transmissible variant emerged with a host of unusual mutations. Now scientists are trying to work out how it evolved.
People in Johannesburg, South Africa, near where cases of Omicron were first identified.
Little more than two months after it was first spotted in South Africa, the Omicron variant of the coronavirus SARS-CoV-2 has spread around the world faster than any previous versions. Scientists have tracked it in more than 120 countries, but remain puzzled by a key question: where did Omicron come from?
There’s no transparent path of transmission linking Omicron to its predecessors. Instead, the variant has an unusual array of mutations, which it evolved entirely outside the view of researchers. Omicron is so different from earlier variants, such as Alpha and Delta, that evolutionary virologists estimate its closest-known genetic ancestor probably dates back to more than a year ago, some time after mid-2020. “It just came out of nowhere,” says Darren Martin, a computational biologist at the University of Cape Town, South Africa.
The question of Omicron’s origins is of more than academic importance. Working out under what conditions this highly transmissible variant arose might help scientists to understand the risk of new variants emerging, and suggest steps to minimize it, says Angela Rasmussen, a virologist at the University of Saskatchewan Vaccine and Infectious Disease Organization in Saskatoon, Canada. “It’s very difficult to try to mitigate a risk that you can’t even remotely wrap your head around,” she says.
The World Health Organization’s recently formed Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) met in January to discuss Omicron’s origins. The group is expected to release a report in early February, according to Marietjie Venter, a medical virologist at the University of Pretoria in South Africa, who chairs SAGO.
Ahead of that report, scientists are investigating three theories. Although researchers have sequenced millions of SARS-CoV-2 genomes, they might simply have missed a series of mutations that eventually led to Omicron. Alternatively, the variant might have evolved mutations in one person, as part of a long-term infection. Or it could have emerged unseen in other animal hosts, such as mice or rats.
For now, whichever idea a researcher favours “often comes down to gut feeling rather than any sort of principled argument”, says Richard Neher, a computational biologist at the University of Basel in Switzerland. “They are all fair game,” says Jinal Bhiman, a medical scientist at the National Institute for Communicable Diseases in Johannesburg, South Africa. “Everyone has their favourite hypothesis.”
Researchers agree that Omicron is a recent arrival. It was first detected in South Africa and Botswana in early November 2021; retrospective testing has since found earlier samples from individuals in England on 1 and 3 November, and in South Africa, Nigeria and the United States on 2 November. An analysis of the mutation rate in hundreds of sequenced genomes, and of how quickly the virus had spread through populations by December, dates its emergence to not long before that — around the end of September or early October last year. In southern Africa, Omicron probably spread from the dense urban province of Gauteng, between Johannesburg and Pretoria, to other provinces and to neighboring Botswana.
But because Johannesburg is home to the largest airport on the African continent, the variant could have emerged anywhere in the world — merely being picked up in South Africa because of the country’s sophisticated genetic surveillance, says Tulio de Oliveira, a bioinformatician at the University of KwaZulu-Natal in Durban and at Stellenbosch University’s Centre for Epidemic Response and Innovation, who has led South Africa’s efforts to track viral variants, including Omicron.
What stands out about Omicron is its remarkable number of mutations. Martin heard about it when he took a phone call from de Oliveira, who asked him to look at the craziest SARS-CoV-2 genome he had ever seen.
The variant has more than 50 mutations when compared with the original SARS-CoV-2 virus isolated in Wuhan, China. Some 30 of these contribute to changes in amino acids in the spike protein, which the coronavirus uses to attach to and fuse with cells. Previous variants of concern have had no more than ten such spike mutations. “That is a hell of a lot of changes,” says Neher.
Researchers have seen many of these mutations before. Some were previously known to give the virus an increased ability to bind to the ACE2 receptor protein — which adorns host cells and is the docking point for SARS-CoV-2 — or to help it evade the body’s immune system. Omicron forms a stronger grip on ACE2 than do previously seen variants. It is also better at evading the virus-blocking ‘neutralizing’ antibodies produced by people who have been vaccinated, or who have been infected with earlier variants. Other changes in the spike protein seem to have modified how Omicron enters cells: it appears to be less adept at fusing directly with the cell’s membrane, and instead tends to gain entry after being engulfed in an endosome (a lipid-surrounded bubble).
But more than a dozen of Omicron’s mutations are extremely rare: some have not been seen at all before, and others have popped up but disappeared again quickly, presumably because they gave the virus a disadvantage.
Another curious feature of Omicron is that, from a genomic viewpoint, it consists of three distinct sublineages (called BA.1, BA.2 and BA.3) that all seem to have emerged at around the same time — two of which have taken off globally. That means Omicron had time to diversify before scientists noticed it. Any theory about its origins has to take this feature into account, as well as the number of mutations, notes Joel Wertheim, a molecular epidemiologist at the University of California, San Diego.
Researchers have explained the emergence of previous variants of concern through a simple process of gradual evolution. As SARS-CoV-2 replicates and transmits from person to person, random changes crop up in its RNA sequence, some of which persist. Scientists have observed that, in a given lineage, about one or two single-letter mutations a month make it into the general viral circulation — a mutation rate about half that of influenza. It is also possible for chunks of coronavirus genomes to shuffle and recombine wholesale, adds Kristian Andersen, an infectious-disease researcher at Scripps Research in La Jolla, California. And viruses can evolve faster when there is selection pressure, he says, because mutations are more likely to stick around if they give the virus an increased ability to propagate under certain environmental conditions.
Some scientists think that person-to-person spread would not be conducive to accumulating as many changes as Omicron has since mid-2020. “It does seem like a year and a half is a really short period of time for that many mutations to emerge and to apparently be selected for,” says Rasmussen.
But Bhiman argues that enough time has elapsed. She thinks the mutation process could have occurred unseen, in a region of the world that has limited genomic sequencing and among people who don’t typically get tested, perhaps because they didn’t have symptoms. At some point in the past few months, she says, something happened to help Omicron explode, maybe because the progress of other variants — such as Delta — was gradually impeded by the immunity built up from vaccination and previous infection, whereas Omicron was able to evade this barrier.
Although researchers have submitted almost 7.5 million SARS-CoV-2 sequences to the GISAID genome database, hundreds of millions of viral genomes from people with COVID-19 worldwide have not been sequenced. South Africa, with some 28,000 genomes, has sequenced less than 1% of its known COVID-19 cases, and many nearby countries, from Tanzania to Zimbabwe and Mozambique, have submitted fewer than 1,000 sequences to GISAID.
Martin says that researchers need to sequence SARS-CoV-2 genomes from these countries to get a better sense of the likelihood of unobserved evolution. It is possible that the three sublineages of Omicron each separately arrived in South Africa from a region with limited sequencing capacity, he says.
But de Oliveira says the scenario that Omicron evolved unseen through person-to-person transmission is “extremely implausible”. Intermediate steps in Omicron’s evolution should have been picked up in viral genomes from people travelling from countries that do little sequencing to those that do a lot.
“This is not the nineteenth century, where you take six months to go from point to point by sailboat,” says Sergei Pond, a computational evolutionary biologist at Temple University in Philadelphia, Pennsylvania.
And Andersen adds that, because some of Omicron’s mutations haven’t been seen before, the variant might have evolved in an environment not involving person-to-person chains of transmission. Some of the changes in Omicron don’t match any seen even in the broader viral group of sarbecoviruses, which includes the virus that causes severe acute respiratory syndrome (SARS). For example, one particular site on the genomes of all known sarbecoviruses encodes a serine amino acid, but a mutation in Omicron means the variant has a lysine at that position, which changes the biochemistry of that region, Andersen says.
However, says Jesse Bloom, a viral evolutionary geneticist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, SARS-CoV-2 has not yet explored all of its possibilities in people. “The virus is still expanding in the evolutionary space.”
An alternative incubator for fast-paced evolution is a person with a chronic infection. There, the virus can multiply for weeks or months, and different types of mutation can emerge to dodge the body’s immune system. Chronic infections give the virus “the opportunity to play cat and mouse with the immune system”, says Pond, who thinks it is a plausible hypothesis for Omicron’s emergence.
Such chronic infections have been observed in people with compromised immune systems who cannot easily get rid of SARS-CoV-2. For example, a December 2020 case report described a 45-year-old man with a persistent infection. During almost five months in its host, SARS-CoV-2 accumulated close to a dozen amino-acid changes in its spike protein. Some researchers suggest Alpha emerged in someone with a chronic infection, because, like Omicron, it seems to have accumulated changes at an accelerated rate.
“The virus has to change to stick around,” says Ben Murrell, an interdisciplinary virologist at the Karolinska Institute in Stockholm. The receptor-binding domain, where many of Omicron’s mutations are concentrated, is an easy target for antibodies, and probably comes under pressure to change in a long-term infection.
But none of the viruses from individuals with chronic infections studied so far has had the scale of mutations observed in Omicron. Achieving that would require high rates of viral replication for a long time, which would presumably make that person very unwell, says Rasmussen. “It seems like a lot of mutations for just one person.”
Further complicating the picture, Omicron’s properties could stem from combinations of mutations working together. For example, two mutations found in Omicron — N501Y together with Q498R — increase a variant’s ability to bind to the ACE2 protein by almost 20 times, according to cell studies. Preliminary research by Martin and his colleagues suggests that the dozen or so rare mutations in Omicron form three separate clusters, in which they seem to work together to compensate for the negative effects of any single one.
If this is the case, it means that the virus would have to replicate sufficiently in a person’s body to explore the effects of combinations of mutations — which would take longer to achieve than if it were sampling the space of possible mutations one by one.
One possibility is that multiple individuals with chronic infections were involved, or that Omicron’s ancestor came from someone with a long-term infection and then spent some time in the general population before being detected. “There are a lot of open questions,” says Rasmussen.
Proving this theory is close to impossible, because researchers would need to be lucky enough to find the particular person or group that could have sparked Omicron’s emergence. Still, more comprehensive studies of SARS-CoV-2’s evolution in chronic infections would help to map out the range of possibilities, says Neher.
Mouse or rat
Omicron might not have emerged in a person at all. SARS-CoV-2 is a promiscuous virus: it has spread to a wild leopard, to hyenas and hippopotamuses at zoos, and into pet ferrets and hamsters. It has caused havoc in mink farms across Europe, and has infiltrated populations of white-tailed deer throughout North America. And Omicron might be able to enter a broader selection of animals. Cell-based studies have found that, unlike earlier variants, Omicron’s spike protein can bind to the ACE2 protein of turkeys, chickens and mice.
One study found that the N501Y–Q498R combination of mutations allows variants to bind tightly to rat ACE2. And Robert Garry, a virologist at Tulane University in New Orleans, Louisiana, notes that several other mutations in Omicron have been seen in SARS-CoV-2 viruses adapting to rodents in laboratory experiments.
The types of single-nucleotide substitution observed in Omicron’s genome also seem to reflect those typically observed when coronaviruses evolve in mice, and do not match as well with the switches that are observed in coronaviruses adapting to people, according to a study of 45 mutations in Omicron. The study noted that, in human hosts, G to U substitutions tend to occur in RNA viruses at a higher rate than C to A switches do, but that Omicron does not show this pattern.
It is possible, then, that SARS-CoV-2 could have acquired mutations that gave it access to rats — jumping from an ill person to a rat, possibly through contaminated sewage — and then spread and evolved into Omicron in that animal population. An infected rat could later have come into contact with a person, sparking the emergence of Omicron. The three sublineages of Omicron are sufficiently distinct that, according to this theory, each would represent a separate jump from animal to human.
A large population of animals with infections lasting longer than in humans could give SARS-CoV-2 room to explore a wide diversity of mutations and “build up a large ghost population of viruses that no one knows about”, says Martin, who says he finds this ‘reverse zoonosis’ theory convincing. Changes that make the virus better at spreading in its animal host won’t necessarily affect its ability to infect people, he says.
An animal reservoir could also explain why some of the mutations in Omicron have been rarely seen before in people, says Andersen.
In the dark
But others say that even a single viral jump from an animal to a person is a rare event — let alone three. Meanwhile, the virus has had plenty of opportunities to slip between people. And although some of Omicron’s mutations have been seen in rodents, that doesn’t mean they can’t happen or haven’t occurred in people, too, and have simply been missed.
Murrell also points out that SARS-CoV-2 didn’t immediately go through a period of accelerated evolution after jumping to people for the first time. When it spread to mink and deer, it did pick up changes, but not as many mutations as Omicron has accumulated, says Spyros Lytras, an evolutionary virologist at the University of Glasgow, UK. This means that the evidence isn’t sufficient to suggest Omicron’s predecessor would have undergone rapid selection after finding a new home in the wild.
To confirm this theory, researchers would need to find close relatives of Omicron in another animal, but they haven’t been looking — “something that has been horribly neglected”, says Martin. Since the pandemic began, researchers have sequenced fewer than 2,000 SARS-CoV-2 genomes isolated from other animals, mostly from mink, cats and deer.
Now that Omicron has taken off, how it evolves in people could offer more clues about its origins. It might, for instance, shed mutations that, in retrospect, are found to have helped it adapt to a different animal host, or in a person with a chronic infection. But it could also not change by much, leaving researchers in the dark.
The answer to Omicron’s emergence will probably be one or a combination of the three scenarios, says Bloom. But, he adds, researchers are far from explaining the processes that brought Omicron here, let alone predicting what the next variant will look like.
And many scientists say they might never find out where Omicron came from. “Omicron really shows us the need for humility in thinking about our ability to understand the processes that are shaping the evolution of viruses like SARS-CoV-2,” says Bloom.
Will Omicron end the pandemic? Here’s what experts say
The variant’s rapid spread, different vaccine strategies and varying levels of immunity worldwide make the pandemic’s future difficult to model.
On 11 January, just seven weeks after the Omicron variant was first reported, the World Health Organization (WHO) warned of a “tidal wave” of infection washing from west to east across the world. Fifty of the 53 countries in Europe and central Asia had reported cases of Omicron, said Hans Henri Kluge, the WHO’s regional director for Europe.
Countries would have to cope as best they could, he said, guided by their individual epidemiological situation, available resources, vaccination-uptake status and socio-economic context. In recent weeks, countries in Europe and the United States have felt the full force of the Omicron wave; in the United Kingdom, which has reported most infections, daily COVID-19 cases peaked at more than 160,000 earlier this month. Scientists there say all nations are facing the same major problem: the sheer speed at which the variant spreads.
And although the WHO and others have suggested that huge numbers of omicron infections could signal the end of the pandemic, because of the short-term surge in immunity that will follow, researchers warn that the situation remains volatile and difficult to model.
“It moves so fast that it gives very little time to prepare any kind of response. So, decisions have to be made under huge uncertainty,” says Graham Medley, an infectious-diseases modeller at the London School of Hygiene & Tropical Medicine, who advises the UK government.
Numbers of Omicron infections can double in less than two days, which is significantly faster than previous SARS-CoV-2 variants and closer to what public-health officials would expect from the milder influenza virus. “Omicron is flu on acid,” one scientist says.
“We haven’t seen that speed before, and it meant you couldn’t vax your way out of it,” adds Christina Pagel, a health-care data analyst at University College London. “Even if you could vax everybody, it still takes two weeks for the vaccine to kick in, and by then you’re in the middle of it.”
That places policymakers and the researchers who advise them in an unenviable position. “It was a situation where you either put in restrictions very, very early, or you do nothing,” Pagel says. “But if you wait to see what happens, then it’s too late.”
Along with other countries, Britain tightened regulations in December. But it was a controversial move, particularly because reports from South Africa, which was hit by Omicron the previous month, suggested that the variant seemed to cause less severe illness and hospitalization — a conclusion now supported by the experience of the United Kingdom and other places.
Difficult to model
UK modellers were initially torn about how to use information from South Africa. It’s relatively straightforward to update a computer model to account for changes in the biological properties of a new variant. However, as the pandemic has progressed, it has become much harder to simulate the baseline immune response of a country’s population, and so to judge how that will limit spread.
In the early days of the pandemic, researchers could assume that most people worldwide were equally susceptible to infection, because COVID-19 was a new disease and no vaccines were available. But 12 months of different vaccine strategies, types and take-up rates from country to country, as well as fluctuating rates of infection and recovery, have left a diverse immunological landscape.
“The probability that infection will put someone in hospital is absolutely a key parameter. But we are now estimating that in an obviously not naive population,” says Mark Woolhouse, an infectious-disease epidemiologist at the University of Edinburgh, UK, who also advises the government. “When you are making those sorts of estimates, formally you really should remake them for every population you’re interested in. And that applies everywhere.”
Modellers were confounded by the lack of specifics in South African data about reduced severity. “There was no quantitative analysis,” Woolhouse says. “So, what numbers do you plug in? Are you saying 10% less pathogenic, or 50% less, or 90% less?”
Still, speaking in a personal capacity, Woolhouse says that some influential modellers in the United Kingdom were wrong not to allow for any reduced severity, instead working with assumed hospitalization rates for Omicron that were identical to those of previous variants. “That’s clearly a pessimistic assumption,” he says. “I do think it could have been much clearer from the beginning that there was this possibility it was less pathogenic and, you know, being crystal clear on what the policy implications of that difference might be.”
The heterogeneity in immunological baselines and other important factors, such as population dynamics from country to country, make it difficult to predict international spread of Omicron with any precision, or to assess — for example — how the variant might take hold in countries with lower vaccination rates. “It’s very hard to answer that question,” says Julian Tang, a consultant virologist at the Leicester Royal Infirmary, UK. “And it’s not very useful, because if you say it’s spreading in pattern XYZ across western Europe and then ABC across North America and MNO in Africa, that doesn’t really help anybody.”
The waning protection against infection that vaccines offer against Omicron also complicates the picture. Laboratory studies have indicated that inactivated-virus vaccines, which make up almost half of the ten billion doses distributed worldwide, elicit few antibodies against the variant. Does that mean that Omicron will rip through places that rely on these shots even faster?
Not necessarily, says Woolhouse. “The inactivated-virus vaccines might induce a broader immunity that would react to a wider range of strains because it will elicit immune responses against viral proteins other than spike, which is particularly variable,” he says. “It’s a very interesting question but I simply haven’t seen a formal analysis of it yet.”
That’s because there are few real-world data to go on. “It’s only just hitting countries that have used them,” says Pagel.
Among the countries that rely on inactivated-virus vaccines, Omicron seems to be making the most headway in the Philippines, which saw an exponential rise in COVID-19 cases this month, particularly in Manila. The number of new infections in the capital does seem to be dropping, but the virus is spreading farther afield. “Definitely cases are slowing down in the [National Capital Region], but in other regions it is now increasing,” said Maria Rosario Vergeire, health spokesperson for the Philippine government.
Vaccination rates are still relatively low in the Philippines, with just 53% of the population fully vaccinated. Officials there say they want to vaccinate all the country’s 77 million adults by May.
Although vaccines are likely to continue protecting against severe symptoms, Pagel says, infection will continue to spread. “I think the assumption is that none of the vaccines are going to give you long-lasting protection against infection,” she says.
Tang agrees: “I don’t think vaccines are the way this pandemic is going to end.”
When will it end?
So, how will it end? Not with Omicron, researchers predict. “This will not be the last variant, and so the next variant will have its own characteristics,” Medley says.
Given that the virus is unlikely to disappear completely, COVID-19 will inevitably become an endemic disease, scientists say. But that’s a slippery concept, and one that means different things to different people. “I think it’s the expectation that the general behavior is somehow towards the situation where we have so much immunity in the population that we would no longer see very deadly epidemics,” says Sebastian Funk, an epidemiologist at the London School of Hygiene & Tropical Medicine.
The transition to endemicity, or “living with the virus” without restrictions and safeguards, is difficult to model with any accuracy, he adds. That’s partly because even the best disease models struggle to make sensible forecasts beyond a few weeks ahead. It’s also because endemicity reflects a judgement call on how many deaths societies are willing to tolerate while the global population steadily builds up immunity.
For Woolhouse, COVID-19 will truly become endemic only when most adults are protected against severe infection because they have been exposed multiple times to the virus as children, and so have developed natural immunity. That will take decades, and it means many older people today (who were not exposed as children) will remain vulnerable and might need continued vaccinations.
That strategy has its flaws. Some of those exposed as children will develop long COVID. And it relies on children continuing to show much lower rates of severe illness as variants evolve.
There are no guarantees that the next variant will be milder, but Tang says that seems to be the pattern so far. “This virus is getting milder and milder with each iteration,” he says.
COVID reinfections surge during Omicron onslaught
Immunity acquired through previous infection is less effective against Omicron than against other variants, but the risk of severe COVID-19 remains low.
Since the Omicron variant of SARS-CoV-2 was first detected, the number of people reinfected with the coronavirus has been rising sharply — a trend that was not observed with previous variants. Researchers say that the new variant is probably driving the surge because it is able to evade the body’s immune defences.
“The situation now is really different. We’re talking about a variant with lots of immune-evasive properties,” says Laith Abu-Raddad, an infectious-disease epidemiologist at Weill Cornell Medicine–Qatar in Doha.
Studies have shown that the variant can outwit immunity induced by vaccination. Now Abu-Raddad and others are revealing how well Omicron can evade antibodies produced during previous SARS-CoV-2 infections. “The ability of Omicron to infect people with either vaccine- or infection-derived immunity is a key part of what made the recent surge so large,” says Marm Kilpatrick, an infectious-disease researcher at the University of California, Santa Cruz.
Understanding reinfection rates is crucial for assessing “how infections might surge and if hospitals will be able to cope”, says Catherine Bennett, an epidemiologist at Deakin University in Melbourne, Australia.
The first signs of Omicron’s immune-evasive properties came from data collected in South Africa, says Bennett. In November last year, researchers showed higher-than-expected rates of reinfection compared with those of previous waves. Similar trends have now been documented elsewhere.
In England, more than 650,000 people have probably been infected twice; most of them were reinfected in the past two months, according to data collected by the UK Health Security Agency (see ‘Rising reinfections’). The agency considers an infection a ‘possible reinfection’ if it took place at least three months after a previous one, but does not confirm that these are separate instances through genetic sequencing of the virus. Before mid-November, reinfections accounted for about 1% of reported cases of COVID-19, but the rate has now increased to around 10%.
The UK Office for National Statistics in Newport has also seen a sharp increase in possible reinfections in recent months, as part of its random sampling of households across the country. The survey counts a possible reinfection if four months have passed since the previous one. The reinfection risk was 16 times higher between mid-December last year and early January this year when Omicron dominated, than in the 7 months leading up to December when Delta was the dominant variant.
Such surveys could be underestimating the true rate of reinfection because some infections go undiagnosed, and some could have happened sooner after the first infection — especially in countries where cases of Omicron quickly followed a Delta wave, says Bennett.
Multiple factors could explain the spike in reinfections, she says. With more people now already exposed to the virus, there is a higher chance of seeing reinfections. Omicron’s speedy spread also increases the chance. But the variant’s ability to evade immunity is probably playing a part, says Bennett.
In a correspondence published in The New England Journal of Medicine this month, Abu-Raddad and his colleagues measured the extent to which Omicron could evade immunity, as part of a nationwide study of infections in Qatar since the start of the pandemic. They found that although having previously been infected was around 90% effective at preventing an infection with the Alpha, Beta or Delta variants, it was only 56% effective against Omicron.
However, Abu-Raddad is encouraged by the results. Most reinfections occurred about one year apart, showing that a previous infection offers immunity for some time. And protection against severe COVID-19 caused by Omicron remained high, at around 88%.
But Shabir Madhi, a vaccinologist at the University of the Witwatersrand in Johannesburg, South Africa, says that the study probably missed many infections that were asymptomatic or mild and were therefore not recorded, so it might be overestimating the effectiveness of a previous infection against Omicron. He expected much lower protection against infection. Laboratory studies have shown that Omicron can successfully evade virus-blocking antibodies generated from earlier variants, which are a good proxy for protection against infection.
Ultimately, Abu-Raddad says that studying reinfections will help researchers to understand what SARS-CoV-2’s transition to an endemic virus will look like.
The 3 main theories for Omicron’s origins
Scientists are trying to pinpoint where and how the highly transmissible variant emerged so they can be better prepared for the next one.
Omicron’s arrival in November 2021 took scientists by surprise. Not because there was a new variant on the block, but because it had many and unusual mutations—some rare and others that had never been seen before. Also, its closest relatives weren’t recent variants but earlier versions of SARS-CoV-2, the virus that causes COVID-19, circulating more than a year ago.
That left the scientific community wondering where, exactly, Omicron came from. Some research suggests that this variant may have evolved in the body of someone who was immunocompromised; other molecular clues suggest that the virus jumped from a human to an animal where it evolved before jumping back into a human host.
It’s normal for a virus to mutate as it spreads from person to person, inevitably producing errors in its genetic code as it multiples. While most mutations may be benign, if any give the virus a survival advantage by making it, say, more transmissible or by aiding its ability to escape the host’s immune system, it may persist and result in new variants with more worrying traits.
“I don’t think other variants of concern are that much of a surprise compared to Omicron, which kind of came out of nowhere,” says Angela Rasmussen, a virologist at the University of Saskatchewan in Canada.
Analysis of its genome suggests that Omicron likely diverged from the original SARS-CoV-2 lineage in mid-2020. The SARS-CoV-2 virus typically acquires two mutations per month. For every lineage that’s been in circulation, “that [rate of mutation] has been pretty constant,” says Francois Balloux, a computational biologist at the University College London Genetics Institute in the United Kingdom. Over the course of about 18 months, that rate of mutation would suggest that the divergent virus strain would have acquired roughly 36 mutations.
But sequencing the Omicron’s genetic code revealed more than 50 mutations, of which at least 30 are in its critically important spike protein, which is essential for infecting human cells. “That’s a big jump,” Balloux says. Also, many of these mutations are clustered around the region in the spike where antibodies bind, blocking the ability of SARS-CoV-2 to enter the cell.
“All of them in a constellation like that,” says Rasmussen, “was certainly very different to anything we’ve been seeing circulating in the human population.”
Prolonged COVID-19 infections
Over the last two years, reports of COVID-19 infections that can persist for months to nearly a year in certain immunocompromised people have emerged. In the absence of a robust immune system, the virus can keep multiplying and pile up mutations that change its appearance and enable it to escape from antibodies produced to block infection.
“We know from other viruses, when you have an infection in an immunocompromised person, the lineage can accumulate more mutations than expected compared to the virus transmitting from person to person,” Balloux says.
New combinations of mutations can emerge, especially when an individual’s immune system doesn’t swiftly eradicate new viruses. Then certain individual mutations that otherwise might not survive are enshrined in the virus’s genetic code and accumulate under low immunity. Some of these individual mutations together could benefit the virus, he says.
In South Africa, for instance, virologist Tongai Maponga at Stellenbosch University and his colleagues recorded more than 20 mutations in a SARS-CoV-2 Beta variant that evolved over at least nine months in a patient struggling with advanced HIV disease. Scientists in the U.K. recorded novel mutations in three other patients with advanced HIV who had been harboring a SARS-CoV-2 Alpha infection for several months. In Portugal, scientists recorded unusually high number of SARS-CoV-2 mutations in an immunocompromised cancer patient whose infection persisted for at least six months and who was treated with the antiviral drug remdesivir and anti-inflammatory corticosteroids. These drugs may have suppressed the patient’s immune system and made it easier for SARS-CoV-2 to mutate and adapt.
Observing the evolution of SARS-CoV-2 in certain immunocompromised patients infected for longer durations, “we have some similarities and mutations that we’ve seen in variants of concern,” says Richard Lessells, an infectious disease physician at the University of KwaZulu-Natal in South Africa. That’s probably how Omicron evolved, according to some scientists.
Although it’s unclear how common such long-lasting COVID-19 infections may be in human populations, especially when several such patients are asymptomatic, Lessells says, “it doesn’t really matter—even if it’s an extremely rare event, if variants emerge that can then successfully spread into a population, then in only has to happen once or twice for that to be significant.”
This could also explain why genomic surveillance efforts in many parts of the world may not have detected a rare SARS-CoV-2 evolution event until it was too late to prevent transmission as the variant infected many people.
Could limited surveillance have let Omicron arise undetected?
But there’s another hypothesis that has gained attention: Perhaps Omicron simply evolved in a relatively isolated region that had limited capacity to analyze the genetic sequences of COVID-19 virus samples. That means Omicron could have circulated undetected in a population for a long time.
For instance, the B.1.620 variant of interest was first detected in Lithuania in April 2021, but researchers traced back its origin to central Africa, where some countries have grappled with limited genomic surveillance capabilities. Although the variant was potentially prevalent in the region, the hypothesis goes, its presence remained undetected and only became knownfrom cases in people who had traveled between Europe and Cameroon and Mali.
Rasmussen, however, thinks this hypothesis may not apply in the case of Omicron. “I think that’s unlikely because there aren’t many populations on Earth that are that isolated,” she says. “We would have seen ancestors of Omicron emerging in other populations [over time], and it would have been picked up at some point by genomic surveillance.”
Is Omicron a product of an animal host?
Wenfeng Qian, a geneticist at the Chinese Academy of Sciences, on the other hand, suspects that Omicron may have emerged in an animal—most likely mice and rats. Over the last year, SARS-CoV-2 has infected pet cats, dogs, and ferrets, ravaged mink farms, and spread to tigers and hyenas in zoos and white-tailed deer in the forests of North America.
Although mice initially served as poor hosts for SARS-CoV-2—because the protein receptors on the surface of the rodent cells blocked the virus from binding and entering—a study showed that newer variants like Alpha, Beta, and Gamma had a mutation called N501Y in their spike protein that allowed the virus to infect mice cells in laboratory tests. This mutation also occurs in Omicron. This mutation also occurs in Omicron. There are also a handful of other mutations, associated with rodent adaptation, which are seen in this variant.
Qian and his colleagues studied 45 mutations, including N501Y, in Omicron’s genome and noted that some of them matched the mutations typically seen in coronaviruses evolving in mice. They also found that the mutational signatures of Omicron’s predecessors weren’t consistent with patterns one might observe if SARS-CoV-2 evolved in a human host. RNA viruses, which include SARS-CoV-2, tend to rack up more mutations in which the genetic building block guanine is replaced with one called uracil—a so-called G-to-U mutation—when they infect and evolve in humans. But the limited number of G-to-U mutations in Omicron’s predecessors suggested to Qian it evolved in an animal host. However, with this, “we cannot identify the exact animal,” he says.
It’s possible that SARS-CoV-2 jumped from an infected person to mice or rats, spread among mice and evolved into Omicron, and then infected a human who might have come into contact with such an animal. This would be similar to the case of mink farmers who were infected with a mutated version of SARS-CoV-2 circulating among minks that caught COVID-19 from a human.
Still, many scientists support the hypothesis that Omicron may have evolved in an immunocompromised person with a prolonged COVID-19 infection. “The type of mutations we see in particular in poorly or untreated HIV patients are very reminiscent of Omicron,” Balloux says. Rasmussen agrees, but to her it doesn’t disprove the animal origin hypothesis or erase the potential risks from exposure to infected animals.
Maponga, Lessells, and their colleagues in South Africa are planning to closely monitor the trajectory of the SARS-CoV-2 virus in severely immunocompromised HIV patients. Rasmussen and her colleagues, on the other hand, are planning to survey domestic animals like horses, cows, sheep, and goats, as well as wildlife like white-tailed deer, raccoons, and small carnivores in Canada to understand their susceptibility to SARS-CoV-2, and in particular Omicron infections.
Finding the origin of Omicron may not help us get over the pandemic, she says. “But it can improve how we monitor for new variants.”
Why does the Omicron sub-variant spread faster than the original?
Early studies suggest that the BA.2 lineage might prolong the Omicron wave, but won’t necessarily cause a fresh surge of COVID infections.
COVID-19 researchers are rushing to understand why a relative of the main Omicron variant is displacing its sibling in countries around the world.
The variant, known as BA.2, has spread rapidly in countries including Denmark, the Philippines and South Africa in the past few weeks. It follows the initial spread of the BA.1 Omicron variant of the virus SARS-CoV-2, which was first identified in southern Africa in late November and quickly spread worldwide.
A laboratory study1 of BA.2 suggests that its rapid ascent is probably the result of it being more transmissible than BA.1. And other preliminary studies suggest that BA.2 can readily overcome immunity from vaccination and previous infection with earlier variants, although it is not much better than BA.1 at doing so.
If real-world epidemiological studies support these conclusions, scientists think that BA.2 will be unlikely to spark a second major wave of infections, hospitalizations and deaths after Omicron’s initial onslaught.
“It might prolong the Omicron surge. But our data would suggest that it would not lead to a brand-new additional surge,” says Dan Barouch, an immunologist and virologist at Beth Israel Deaconess Medical Center in Boston, Massachusetts, who led the laboratory study, posted on the medRxiv preprint server on 7 February.
BA.2’s steady rise in prevalence in multiple countries suggests that it has a growth advantage over other circulating variants, says Mads Albertsen, a bioinformatician at Aalborg University in Denmark. That includes other forms of Omicron, such as a less-prevalent lineage called BA.3 (see ‘Omicron’s many variants’).
“From a scientific perspective, the question is why,” says Barouch. Researchers think that a large part of the reason Omicron quickly replaced the Delta variant is its ability to infect and spread among people who had been immune to Delta. So one possibility for BA.2’s rise is that it’s even better than BA.1 at overcoming immunity — potentially including the protection gained from a BA.1 infection.
The variants’ differing behaviours could be explained by their many genetic differences. Dozens of mutations distinguish BA.1 from BA.2 — particularly at key portions of the virus’s spike protein, the target of potent antibodies that can block infection. “BA.2 has a whole mess of new mutations that no one has tested,” says Jeremy Luban, a virologist at the University of Massachusetts Chan Medical School in Worcester.
To assess any differences between BA.1 and BA.2, Barouch’s team measured how well ‘neutralizing’, or virus-blocking, antibodies in people’s blood protected cells from infection by viruses with either variant’s spike protein1. The study looked at 24 people who had received three doses of the RNA vaccine made by Pfizer in New York City; they produced neutralizing antibodies that were slightly better at fending off infection by viruses with BA.1’s spike than those with BA.2’s. The same was true for a smaller group of people who had gained immunity from infection during the initial Omicron surge, and in some cases also from vaccination.
The small difference in overall potency against the two variants means that an ability to evade immunity is unlikely to explain BA.2’s ascent worldwide, says Barouch.
The results chime with those from a 9 February preprint2 led by virologist David Ho at Columbia University in New York City, which found that BA.2 and BA.1 had similar abilities to resist neutralizing antibodies in the blood of people who had been vaccinated or previously infected.
But Ho’s team also found signs that genetic mutations unique to BA.2 affect how some antibodies recognize the variant. The researchers found that one family of antibodies that attach to a part of the spike protein that binds to host cells was much less effective at neutralizing BA.2 than BA.1, and another type of spike antibody tended to be more active against BA.2. And a 15 February preprint3 led by virologist Kei Sato at the University of Tokyo found that hamsters and mice infected with BA.1 produced antibodies that were less potent against BA.2 than BA.1.
It’s not yet clear what the latest lab studies mean for immune protection against BA.2 in the real world. Barouch says his team’s study cannot indicate whether people who have recovered from BA.1 are susceptible to BA.2 reinfection. But he thinks his team’s data suggest that such risks are unlikely to be much higher for BA.2 than for BA.1.
According to news reports, researchers in Israel have identified a handful of cases in which people who had recovered from BA.1 became infected with BA.2. Meanwhile, Danish researchers have begun a study to determine how frequently such reinfections occur, says Troels Lillebaek, a molecular epidemiologist at the State Serum Institute in Copenhagen and chair of Denmark’s SARS-CoV-2 Variants Risk Assessment Committee. “If there was no protection, that would be a surprise and, I think, unlikely. We will know for sure within a few weeks.”
Another study, of Omicron spread in more than 8,000 Danish households, suggests that BA.2’s rise results from a mix of factors4. Researchers including Lillebaek found that unvaccinated, double-vaccinated and boosted individuals were all more susceptible to BA.2 infection than to BA.1 infection.
That unvaccinated people are also at heightened risk of BA.2 infection suggests that properties of the virus other than immune evasion are at least partly behind its enhanced transmissibility, says Lillebaek.
In Denmark, where vaccination rates are high, BA.2’s ascent is so far not causing significant problems, says Lillebaek. A preliminary study found that the variant seems to cause no more severe illness than does BA.1, including in children.
But BA.2 could pose greater challenges in places that have lower vaccination rates, says Lillebaek. The variant’s growth advantage over BA.1 means that it could extend Omicron peaks, increasing the odds of infection for older people and other groups at high risk of severe disease. “I think the main problem with BA.2 is even more transmission,” Lillebaek adds. “You risk even more people testing positive within a short time, putting strain on the hospital system.”
Mutation, mutation, mutation
There are also hints that BA.2 could limit treatment options. In laboratory experiments, Ho’s team found2 that the variant was resistant to a therapeutic monoclonal antibody, called sotrovimab, that was effective against BA.1. However, the drug’s manufacturer, Vir Biotechnology in San Francisco, California, said in a press release on 9 February that its own unpublished experiments suggest that sotrovimab remains effective against BA.2.
Identifying the specific properties of BA.2 and the genetic mutations responsible for its growth advantage will be no simple matter, says Luban. In other fast-spreading variants, including Alpha and Delta, researchers have spotted mutations that seem to speed transmission, but these are unlikely to fully explain those variants’ behaviour.
And molecular mechanisms that seem important for other variants’ advantages — such as those that control the virus’s ability to bind tightly to human cells or to quickly fuse its membrane with those of infected cells — might be less crucial in distinguishing between BA.1 and BA.2, adds Luban. “Omicron really slapped a lot of people in the face who thought everything was clear,” he says. “It’s a puzzle.”
Are COVID surges becoming more predictable? New Omicron variants offer a hint
Omicron relatives called BA.4 and BA.5 are behind a fresh wave of COVID-19 in South Africa, and could be signs of a more predictable future for SARS-CoV-2.
Here we go again. Nearly six months after researchers in South Africa identified the Omicron coronavirus variant, two offshoots of the game-changing lineage are once again driving a surge in COVID-19 cases there.
Several studies released in the past week show that the variants — known as BA.4 and BA.5 — are slightly more transmissible than earlier forms of Omicron, and can dodge some of the immune protection conferred by previous infection and vaccination.
“We’re definitely entering a resurgence in South Africa, and it seems to be driven entirely by BA.4 and BA.5,” says Penny Moore, a virologist at the University of the Witwatersrand in Johannesburg, South Africa, whose team is studying the variants. “We’re seeing crazy numbers of infections. Just within my lab, I have six people off sick.”
However, scientists say it is not yet clear whether BA.4 and BA.5 will cause much of a spike in hospitalizations in South Africa or elsewhere. High levels of population immunity — provided by previous waves of Omicron infection and by vaccination — might blunt much of the damage previously associated with new SARS-CoV-2 variants.
Moreover, the rise of BA.4 and BA.5 — as well as that of another Omicron offshoot in North America — could mean that SARS-CoV-2 waves are beginning to settle into predictable patterns, with new waves periodically emerging from circulating strains (see ‘Omicron’s new identities’). “These are the first signs that the virus is evolving differently” compared with the first two years of the pandemic, when variants seemed to appear out of nowhere, says Tulio de Oliveira, a bioinformatician at Stellenbosch University in South Africa, who led one of the studies.
By analysing viral genomes from clinical samples, de Oliveira and his colleagues found1 that BA.4 and BA.5 emerged in mid-December 2021 and early January 2022, respectively. The lineages have been rising in prevalence since then, and currently account for 60–75% of COVID-19 cases in South Africa. Researchers have also identified the variants in more than a dozen other countries, mostly in Europe.
On the basis of the growth in BA.4 and BA.5 case numbers in South Africa — which now average nearly 5,000 per day, from a low of around 1,200 in March — de Oliveira’s team estimates that the variants are spreading slightly faster than the BA.2 sub-lineage of Omicron (which itself was a bit more transmissible than the first Omicron variant, BA.1). The study was posted on the medRxiv preprint server and has not yet been peer reviewed.
The boost in transmissibility is “quite an advantage”, and similar in magnitude to the advantages that some other fast-spreading SARS-CoV-2 variants had over their predecessors, says Tom Wenseleers, an evolutionary biologist at the Catholic University of Leuven in Belgium. “Taking everything together and looking at all the data, it seems a sizeable new infection wave is certain to come.”
Jesse Bloom, a viral evolutionary biologist at Fred Hutch, a research centre in Seattle, Washington, agrees that BA.4 and BA.5 are spreading faster than other Omicron lineages. “What is still unclear is why they are more transmissible,” he says. “One possibility is that they are just inherently better at transmitting.” The other is that the variants are better at eluding immune responses such as antibodies, allowing them to infect people with prior immunity.
Both are closely related to BA.2 — although exactly how is not clear, Bloom adds (see ‘Pathogen progression’). BA.4 and BA.5 both carry a key mutation called F486V in their spike proteins — the viral protein responsible for infection and the prime target of immune responses. Bloom’s team has previously found that this mutation could help variants to dodge virus-blocking antibodies.
Further studies suggest that BA.4 and BA.5 are growing, at least in part, because of their ability to evade immune responses. A team led by virologist Alex Sigal at the Africa Health Research Institute in Durban, South Africa, analysed blood samples from 39 people who had been infected during the first Omicron wave, 15 of whom had been vaccinated2.
In lab experiments, antibodies in these samples were several times less effective at preventing cells from being infected by BA.4 or BA.5 than they were at keeping out the original Omicron strain. However, antibodies produced by people who had been vaccinated were more potent against the new variants than were those from people whose immunity stemmed solely from BA.1 infection. The study was posted on medRxiv.
Another study3, posted on the ResearchSquare preprint server and led by virologist Xiaoliang Xie at Peking University in Beijing, also found that antibodies triggered by BA.1 infection were less potent against BA.4 and BA.5. Moore says the results chime with her unpublished experiments, too.
BA.4 and BA.5’s capacity to escape immunity, although not dramatic, “is enough to cause trouble and lead to an infection wave” — but the variants are not likely to cause disease much more severe than was seen during the previous wave, especially in vaccinated people, Sigal said in a Twitter post. “They clearly have an advantage in antibody escape, which is one contributing factor in why they are spreading,” says Bloom.
Hospitalizations are slowly ticking up in South Africa — from a low of just under 2,000 people in hospital with COVID-19 in early April — but researchers say it’s too soon to tell whether BA.4 and BA.5 will put much pressure on health-care systems. “The hospitals are empty in South Africa and we have high population immunity,” says de Oliveira.
The next wave
Although BA.4 and BA.5 have been detected in several European countries and in North America, the variants might not set off a fresh COVID-19 wave in these places — at least right away. The closely related BA.2 variant has just swept through Europe, so the population’s immunity could still be high, says Wenseleers. “It gives hope that maybe in Europe it will have a smaller advantage and will cause a smaller wave.”
Some parts of North America are also seeing the rise of other Omicron sub-lineages that have spike-protein mutations in some of the same places as in BA.4 and BA.5. One such variant — called BA.2.12.1 — also has the capacity to evade antibodies triggered by a previous Omicron infection and vaccination, according to the study3 led by Xie, and separate work by virologist David Ho at Columbia University in New York City. (Ho hasn’t yet reported his team’s data in a preprint, but has shared them with US government officials.)
The emergence of these strains suggests that the Omicron lineage is continuing to make gains by eroding immunity, says Ho. “It’s pretty clear that there are a few holes in Omicron that are gradually being filled up by these new sub-variants.”
If SARS-CoV-2 continues along this path, its evolution could come to resemble that of other respiratory infections, such as influenza. In this scenario, immune-evading mutations in circulating variants, such as Omicron, could combine with dips in population-wide immunity to become the key drivers of periodic waves of infection. “It is probably what we should expect to see more and more of in the future,” says Moore.
Previous variants, including Alpha, Delta and Omicron, differed substantially from their immediate predecessors, and all emerged, instead, from distant branches on the SARS-CoV-2 family tree.
Wenseleers and other scientists say we shouldn’t rule out more such surprises from SARS-CoV-2. For instance, Delta hasn’t completely vanished and, as global immunity to Omicron and its expanding family increases, a Delta descendant could mount a comeback. Whatever their source, new variants seem to emerge roughly every six months, notes Wenseleers, and he wonders whether this is the structure that COVID-19 epidemics will settle into.
“That is one way to read the patterns that have been observed so far,” says Bloom. “But I think we should be cautious in extrapolating general rules from a fairly short observation time frame.”
Two new Omicron variants are spreading. Will they drive a new U.S. surge?
The subvariants BA.4 and BA.5 may dodge immunity, especially in unvaccinated people, possibly causing a spike in infections worldwide.
Two new Omicron variants are spreading. Will they drive a new U.S. surge?
The subvariants BA.4 and BA.5 may dodge immunity, especially in unvaccinated people, possibly causing a spike in infections worldwide.
Two new Omicron variants are spreading. Will they drive a new U.S. surge?
The subvariants BA.4 and BA.5 may dodge immunity, especially in unvaccinated people, possibly causing a spike in infections worldwide.
New versions of Omicron are again causing a surge of COVID-19 cases in South Africa, and studies show that these new subvariants are so different from the original version of Omicron that immunity generated from a previous infection may not provide much protection.
Dubbed BA.4 and BA.5, the new subvariants are nearly identical to each other, and both are more transmissible than the Omicron BA.2 subvariant. In South Africa, they replaced the BA.2 strain in less than a month. They are now responsible for a spike in South Africa’s COVID-19 cases, which have tripled since mid-April.
“If you were unvaccinated, what you got is almost no immunity to BA.4 and BA.5,” says Alex Sigal, a virologist at the Africa Health Research Institute and at the University of KwaZulu-Natal. “There might be some immunity that may be enough to protect against severe disease, but not sufficient to protect against symptomatic infection.”
South Africa is the worst hit country on the continent, with more than 100,523 official deaths from COVID-19—and that’s likely a gross underestimate according to a recent study in The Lancet. With BA.4 and BA.5 now on the rise, the death toll is likely to grow, as only a third of the South African population has received a COVID-19 vaccine; the rate of vaccination is even lower in the rest of Africa.
For now, the subvariant known as BA.2.12.1 remains dominant in the U.S., causing new hospitalizations to spike in the last week by more than 17 percent nationally and by as much as 28 percent in the Great Lakes area, and Washington D.C. and the surrounding region. But the new subvariants have spread to more than 20 countries across North America, Asia, and Europe, and already 19 cases of BA.4 and six cases of BA.5 have been identified in the U.S.
How are BA.4 and BA.5 different from other Omicron variants?
South Africa has become a bright spot within Africa for sequencing samples of SARS-CoV-2. This swift sequencing was critical in alerting the world in December 2021 to the discovery and surge of the original Omicron strain, called BA.1. Now the same team has discovered BA.4 and BA.5.
“The BA.4 and BA.5 sub-variants were identified because South Africa is still doing the vital genetic sequencing that many other countries have stopped doing,” said Tedros Adhanom Ghebreyesus, the Director General of the World Health Organization, at a press conference on May 4. “In many countries we’re essentially blind to how the virus is mutating. We don’t know what’s coming next.”
That sequencing has revealed that for both BA.4 and BA.5, the spike protein is similar to the one in BA.2, except for six mutations. The spike protein is the part of the SARS-CoV-2 virus that anchors to receptors on human respiratory cells and allows the virus to infect the cell.
“The three modifications present in the spike of BA.4 and BA.5, compared to BA.2, are most likely associated to antibody escape and improved viral fitness and binding to the ACE2 receptor,” says Olivier Schwartz, head of the Virus and Immunity Unit at Institut Pasteur in France.
Two of the changes on the spike can make these viruses more infectious, says Ravindra Gupta, an immunologist and infectious diseases specialist at the University of Cambridge in the U.K. as shown by his previous research. The upside is that these same mutations make it easy for researchers to rapidly distinguish the new subvariants from BA.2 in a standard PCR test.
Another mutation present in BA.4 and BA.5 is also found in other variants of concern, including Delta, Kappa, and Epsilon. It increases infectivity and weakens immunity from existing antibodies, according to a preliminary study from China.
The Chinese study also shows that a rare change seen before only 54 times among 10 million viral sequences helps BA.4 and BA.5 to evade BA.1-specific antibodies. This same mutation also enabled SARS-CoV-2 to infect mink and ferrets during April 2020 outbreaks in mink farms.
In addition to these spike protein mutations, BA.4 and BA.5 also have small changes in viral proteins whose exact function are not well known.
Where did BA.4 and BA.5 evolve?
A preliminary genetic analysis estimates that the new subvariants may have originated in South Africa at around the same time as other Omicron variants, in mid-December 2021 and early January 2022, respectively. But scientists don’t yet know their origin for sure.
“BA.4 and BA.5 may well have originated from the same kind of common source as BA.1, BA.2, and BA.3, but it’s not certain,” says Richard Lessells, an infectious diseases doctor at the University of KwaZulu-Natal in Durban, South Africa. He is part of the nation’s sequencing team that discovered all of these Omicron variants.
Possible routes of evolution may have been an animal host, such as a mouse; or it may have gestated in some immunocompromised patients, as has been shown to occur through accumulation of mutations during a chronic infection by Gupta.
“The alternative is that BA.4 and BA.5 may have evolved from BA.2,” says Lessells.
BA.4 and BA.5 dodge previous immunity
In the first study of BA4 and BA.5 on immunity, which has not yet been peer reviewed, scientists led by Sigal, of the Africa Health Research Institute, isolated live viruses from nasal swabs. The scientists then ran tests to see whether antibodies from unvaccinated and vaccinated people who had been infected with the original Omicron BA.1 strain just a few months ago were able to neutralize these new variants. Sigal’s team discovered that these antibodies weren’t able to protect against symptomatic infection.
That’s concerning, because in low- and middle-income countries less than one in six people have yet received a single dose of any COVID-19 vaccine. Even in the United States, nearly 23 percent of the population remains unvaccinated.
“BA.4/5 data are interesting and somewhat surprising,” says Gupta, referring to the sharp decline in immunity seen in studies so far. “It is greater than I would have predicted,” he says. “It may be that [the] biology of this virus has completely changed in terms of how quickly it’s able to evolve.”
The South African study does have some good news for vaccinated people: “We found that you get a lot of protection from vaccines, even if you got infected with Omicron despite being vaccinated—a lot more protection than if you weren’t vaccinated going forward,” says Sigal.
Sigal’s study also suggests that BA.4 and BA.5 may cause less severe disease, especially among vaccinated people, compared to previous Omicron variants. This may explain why fewer people seem to be getting severe disease despite the rise in COVID-19 hospitalizations in South Africa. The median length of hospitalization also appears to be shorter, but deaths due to COVID-19 are rising faster in patients of older age.
“BA.4/5 data do reinforce the need for boosters in vulnerable people to keep the antibody levels high,” says Gupta.
In the meantime, Moderna has published data on its new mRNA-1273.211 candidate booster vaccine—which mixes ancestral spike protein with a mimic of the Beta variant spike. Although not yet peer reviewed, the results seem to show superior protection for up to six months even against the Omicron variant.
“Vaccines are designed to prevent severe disease, to keep us out of hospital and off the ventilator,” says Lessells. “And they are still doing that extremely well, in the face of all these different variants.”
Why call it BA.2.12.1? A guide to the tangled Omicron family
Nature explores how subvariants are named, and why none of Omicron’s family members has been upgraded to a ‘variant of concern’.
For the foreseeable future, the coronavirus SARS-CoV-2 will continue evolving into new variants that lead to waves of infections. In 2020 and 2021, the World Health Organization (WHO) announced the emergence of variants of concern by giving them names from the Greek alphabet. But this year, Omicron has remained in the spotlight, with members of its family — subvariants — fuelling surges as they evade antibodies that people have generated from previous infections and vaccines. For example, the Omicron subvariant BA.2.12.1 is gaining ground in North America, now accounting for about 26% of the SARS-CoV-2 genomes submitted to the GISAID data initiative, and BA.4 and BA.5 are spreading rapidly in South Africa, comprising more than 90% of genomes sequenced.
Given the subvariants’ increasing dominance, Nature spoke to researchers to make sense of the current wonky names, and to learn why the WHO hasn’t given them Greek monikers that could spur policymakers to take stronger action.
How do scientists first identify a variant?
SARS-CoV-2 acquires mutations as it replicates in cells. Technically, this means that millions of variants probably arise every day. But the majority of mutations don’t improve the virus’s ability to survive and reproduce, and so these variants are lost to time — outcompeted by fitter versions.
A small portion of variants do, however, gain traction. When this happens, researchers conducting genomic surveillance flag samples that all have the same set of distinct mutations. To find out whether these samples constitute a new branch on the SARS-CoV-2 family tree, they contact bioinformaticians who have established nomenclature systems for the virus. One popular group, called Pango, consists of about two dozen evolutionary biologists and bioinformaticians who compare the samples’ sequences with hundreds of others using phylogenetic software.
The group’s name derives from a software program called Pangolin, originally created by bioinformatician Áine O’Toole at the University of Edinburgh, UK. If the analysis suggests that the new samples derived from the same recent common ancestor, it means that they are a distinct lineage on the coronavirus tree. In determining whether to name the lineage, Pango considers whether the variants have appeared more frequently over time, and whether their mutations are in regions of the virus that might give it a competitive edge. At this point, a lineage label doesn’t indicate risk. Rather, it allows scientists to keep an eye on a variant and learn more.
“We want to name everything that jumps out at us at an early stage so that we can define it and track it, and see if it is growing quickly relative to other lineages,” says Andrew Rambaut, an evolutionary biologist at the University of Edinburgh and a member of Pango. “You probably won’t hear of most of the lineages we name,” he says, because they couldn’t compete with other versions of SARS-CoV-2 and have disappeared.
How are variants named?
When naming a variant, the Pango committee uses a hierarchical system that indicates the variant’s evolutionary history and when it was detected relative to others. The initial letters in the name reflect when Pango gave the lineage a label, following in a sequence from A to Z, then from AA to AZ, BA to BZ, and so on. Separated by a full stop, the next numbers indicate the order of branches from that lineage. For example, BA.1, BA.2, BA.3, BA.4 and BA.5 are the first five branches descending from an original Omicron ancestor. And BA.2.12.1 is the 12th lineage to branch off from BA.2, and then the first named branch on that 12th bush. All subvariants are variants, but researchers use the former term when they want to imply that the lineages belong to a larger grouping, such as Omicron.
If a variant evades the immune system much more effectively than others in circulation, causes more severe disease or is much more transmissible, the WHO might determine it to be a ‘variant of concern’ and change its name to a Greek letter (see ‘Evolution of a virus’). For instance, the multiple concerning mutations in a variant labelled as B.1.1.529 last year, coupled with its rapid rise, prompted the WHO to change its name to Omicron in November 2021. Whereas Pango’s technical names are meant to help researchers track SARS-CoV-2 evolution, the WHO’s system places a priority on the ease of communication to the public.
Given all these variants, is SARS-CoV-2 evolving more rapidly than other viruses?
Not necessarily, Rambaut says. Researchers are finding an incredible amount of diversity in SARS-CoV-2, but they’re also sequencing this virus at an unprecedented rate. A record 11 million SARS-CoV-2 genomes have been uploaded to the popular GISAID data platform since January 2020. By contrast, researchers have uploaded about 1.6 million sequences of the influenza virus to GISAID’s EpiFlu database since May 2008.
Still, Rambaut says, many questions remain about how SARS-CoV-2 is evolving, because sequencing is nearly absent in some parts of the world, and some countries with raging outbreaks are scaling back genomic surveillance.
Could Omicron’s subvariants, such as BA.4, eventually receive Greek names?
Yes, although it hasn’t happened yet. Some researchers argue that the Omicron subvariants currently fuelling surges, such as BA.4 and BA.2.12.1, deserve simpler names to aid communication with governments and the public at a time when regard for COVID-19 control measures, such as face masks, is waning. They also point out that unlike Delta’s subvariants — which were not discussed much in the media — BA.4 and BA.2.12.1 can overcome immunity provided by earlier infections with other Omicron subvariants. This was unexpected, says Houriiyah Tegally, a bioinformatician at the Centre for Epidemic Response and Innovation in Stellenbosch, South Africa. “Everyone thought that only new variants would cause new waves, but now that we’re seeing that Omicron can do it, maybe we should adapt the system of naming,” she suggests.
But the WHO is so far resisting this idea. WHO virologist Lorenzo Subissi says that the capacity for immune evasion isn’t wildly different between Omicron subvariants. He adds that the agency’s assessment could change if future studies prove that an Omicron subvariant causes more severe disease than other Omicron varieties. The technical lead of the WHO’s COVID-19 response, Maria Van Kerkhove, adds that the agency also doesn’t recommend swapping a technical label for a Greek name in the hope of spurring leaders to take the ongoing pandemic more seriously. “This is already a scary virus, it is still killing huge numbers of people unnecessarily,” she says, suggesting that world leaders should already be paying attention.
How months-long COVID infections could seed dangerous new variants
Tracking SARS-CoV-2 evolution during persistent cases provides insight into the origins of Omicron and other global variants. What can scientists do with this knowledge?
6/15/2022 4:12 PM
These are mutations that accumulated in the spike protein of SARS-CoV-2 during a seven-month-long infection. Illustration by Nik Spencer/Nature;
Virologist Sissy Sonnleitner tracks nearly every COVID-19 case in Austria’s rugged eastern Tyrol region. So, when one woman there kept testing positive for months on end, Sonnleitner was determined to work out what was going on.
Before becoming infected with SARS-CoV-2 in late 2020, the woman, who was in her 60s, had been taking immune-suppressing drugs to treat a lymphoma relapse. The COVID-19 infection lingered for more than seven months, causing relatively mild symptoms, including fatigue and a cough.
Sonnleitner, who is based at a microbiology facility in Außervillgraten, Austria, and her colleagues collected more than two dozen viral samples from the woman over time and found through genetic sequencing that it had picked up about 22 mutations (see ‘Tracking spike’s evolution’). Roughly half of them would be seen again in the heavily mutated Omicron variants of SARS-CoV-2 that surged around the globe months later. “When Omicron was found, we had a great moment of surprise,” Sonnleitner says. “We already had those mutations in our variant.”
Omicron did not arise from the woman’s infection, which doesn’t seem to have spread to anyone. And although no definitive links have been made to individual cases, chronic infections such as hers are a leading candidate for the origins of Omicron and other variants that have driven COVID-19 surges globally. “I don’t think there can be any doubt in anyone’s mind that these are a source of new variants,” says Ravindra Gupta, a virologist at the University of Cambridge, UK.
Researchers want to understand how the virus might evolve the ability to spread from person to person more easily, to evade the immune response, or to become more or less severe. Some or all of these qualities might be forged during the course of a chronic infection. “We don’t quite understand what can evolve in a single individual — and what cannot,” says Alex Sigal, a virologist at the Africa Health Research Institute in Durban, South Africa.
The odds are remote that this knowledge could help to predict the next deadly strain or even to trace variants such as Omicron to their origin. Still, virologists hope that by improving their understanding of viral evolution, they will be able to anticipate what future variants might look like — and potentially find better ways to treat chronic infections. “It’s such an important problem, given that we don’t want another variant that we can’t handle,” says Sigal.
Since late 2019, scientists have sequenced the genomes of more than 11 million samples of SARS-CoV-2 taken from people. These efforts have drawn an evolutionary tree that is remarkable in its breadth, showing how the virus has changed during its march around the planet, gaining just a couple of stable mutations per month as it moves from person to person.
“But that’s only one part of the evolutionary story,” says Sarah Otto, an evolutionary biologist at the University of British Columbia in Vancouver, Canada. Each person’s infection is its own universe, where new mutations arise as the infection spreads from cell to cell. Most of these changes won’t matter to the virus, and many will do it harm. But some might give it a slight advantage over other versions of the virus in that person’s body, enhancing its ability to spread or providing some resistance to immune defenses. These two traits — infectivity and immune evasion — are the main ways in which SARS-CoV-2 has evolved since it first emerged in 2019.
In acute SARS-CoV-2 infections, which generally last a week or two before being cleared by the immune system, versions of the virus with advantageous mutations have little time to outcompete those that lack them. The odds of a virus with such an advantage being transmitted to another individual are therefore small. Studies suggest that only a few virus particles — maybe even just one — are needed to seed a new infection. “Which of those viruses happens to be in the aerosol droplet you sneeze out at the time someone walks by and breathes in is largely a matter of luck,” says Jesse Bloom, a evolutionary biologist at the Fred Hutchinson Cancer Center in Seattle, Washington. “So, most of the beneficial mutations that have arisen in a patient are lost, and then evolution has to start up all over again.”
This ‘transmission bottleneck’ is the reason SARS-CoV-2 picks up around two mutations per month globally, on average. But in chronic infections, which last for weeks to months, viruses with advantageous mutations have time to outcompete others.
Compared with acute cases, these long-term infections also allow time for much more viral diversity to develop. And through a process called recombination, which can shuffle the genomes of SARS-CoV-2 particles together, mutations that are beneficial in one part of the body, such as the upper airways, might show up in viruses bearing other useful properties, says Andrew Rambaut, an evolutionary biologist at the University of Edinburgh, UK. “If the result is a fitter virus, it can suddenly take off.”
As a result of chronic infections, globally, “this virus has opportunities not just to evolve in one way, in one direction, but literally thousands, maybe tens of thousands of directions over months”, Otto says.
No two chronic infections are identical. But in dozens of case reports, researchers have begun to identify common signatures of long-term infection. One of the most striking, says Otto, is the large number of amino-acid changes that accrue in the virus’s spike protein, which helps it to infect cells and is a primary target for the body’s immune response.
Many of these mutations map to regions of the spike that are targeted by antibodies, such as its receptor binding domain (RBD) and the N-terminal domain, which are involved in recognizing and infecting host cells. This makes sense, says Darren Martin, an evolutionary virologist at the University of Cape Town in South Africa. If a person’s immune system fails to clear an infection fully, the surviving viruses are likely to bear immunity-evading mutations that helped them to survive the attack. One study, which has not been peer reviewed, found that the most common mutation in chronic infections is at a position in the spike protein’s RBD called E484. Changes at this site can prevent some potent infection-blocking antibodies from attaching to the virus.
Some mutations don’t work particularly well on their own. Last year, Gupta and his team described a 102-day infection in a man in his 70s who had a compromised immune system, and who ultimately died from the infection. After doctors had treated him with convalescent plasma — the antibody-containing portion of blood donated by people who had recovered from COVID-19 — Gupta’s team found that viruses with a pair of spike-protein mutations were thriving in the man’s airways.
One of the mutations, called D796H, conferred resistance to antibodies — but this benefit came at a cost to the virus. When the researchers engineered a non-replicating ‘pseudotype virus’ to carry the D796H mutation and measured how well it could infect cells in the lab, they found that this mutation alone made the pseudotype virus significantly less infectious. But when the pseudotype virus also contained a second mutation found in the same person — a two-amino-acid deletion at sites 69 and 70 — infectivity was restored almost completely. Such compensatory mutations, which have more time to emerge in chronic infections, allow the virus to make evolutionary leaps, says Gupta. “Viruses struggle to do that when they’re jumping between hosts very quickly.”
In some cases, mutations have made sense only with hindsight. In late 2020, Jonathan Li, a physician-scientist at Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues released the first detailed report of a chronic SARS-CoV-2 infection: an ultimately fatal case in a 45-year-old man who had a rare autoimmune disease. The virus developed mutations linked to antibody resistance, including E484K, and another spike mutation called N501Y, which lab studies had suggested improves the virus’s ability to bind to host-cell receptors, potentially boosting infectivity.
The significance of the N501Y change became apparent when it was detected in a trio of fast-growing lineages later named the Alpha, Beta and Gamma variants of concern (VOCs). Omicron bears this mutation, as well as several others identified in the man’s infection. “He really was the harbinger of what was to come,” Li says.
Seeking variant origins
Alpha, identified in the United Kingdom in late 2020, was the first SARS-CoV-2 variant suspected to have emerged from a chronic infection. But that wasn’t the only possible explanation, says Rambaut. The variant might have arisen in a region — probably outside the United Kingdom — that had little capability to conduct genomic surveillance of SARS-CoV-2. Alternatively, Alpha could have evolved in an animal reservoir (the variant’s N501Y mutation enables it to infect mice, rats and mink).
A chance discovery nevertheless suggests that a chronic infection was the most likely source of Alpha. Rambaut and Verity Hill, an evolutionary biologist at the University of Edinburgh, reported in a March preprint the discovery of an intermediate version of Alpha in UK sequencing data. The sequence was collected from a person in southeast England in July 2020, two months before Alpha was first detected in the same region.
The virus had acquired the N501Y mutation, as well as several other hallmarks of Alpha, but it lacked the full suite of changes. “It’s accumulating these mutations. It was probably a bit rubbish at spreading,” Hill says. Only once the Alpha intermediate gained further mutations did it have the capacity to take off, she suggests.
Combinations of mutations are seen in Omicron, too. That variant — which includes several sub-lineages with many overlapping mutations — is brimming with genetic changes linked to both immune escape and infectivity that had been spotted before. But what stood out to Martin was that the BA.1 subvariant that set off most countries’ Omicron waves has a collection of 13 spike mutations that scientists had rarely seen individually, let alone all together in a single virus.
Martin and his colleagues hypothesize that, among this unique set of mutations, are some that helped to offset the evolutionary costs associated with the mutations that hastened Omicron’s spread. “Those trade-offs take a long time to resolve and those require, in my opinion, chronic infections,” says Martin. These could be in humans or in animals, he adds.
Another characteristic of Omicron — the reduced severity of disease — could also be a product of chronic infection. Lab studies have suggested that Omicron’s relative mildness could be a result of its preference for infecting cells in the upper airways, as opposed to those in the lung. The variant probably evolved from a strain that adeptly infected both upper and lower airways. Gupta suspects that Omicron’s shift probably depended on the kind of coordinated evolution that occurs when a virus spends months in a single person’s body. But what’s not clear are the evolutionary forces that propelled such a shift, he adds.
On the lookout
Chronic infections could be the best explanation for how variants such as Omicron and Alpha evolved. But it’s not obvious how one of the defining characteristics of most variants — their ability to spread like wildfire between people — might evolve in a single individual. “That’s a real mystery,” says Bloom. “When something’s not under selection, you often lose it. During a chronic infection there’s no longer selection for transmissibility.”
One possible explanation is that the same molecular mechanisms that help SARS-CoV-2 to infect a person’s airways, lungs and other organs are also important for enabling the virus to spread to others. “The same transmission dynamics are required when it’s inside you as when it’s going from one person to another,” says Martin.
But there is a difference between a virus that merely retains the ability to transmit, and one such as Omicron or Alpha that can cause a global surge in cases. A massive boost in transmissibility or the capacity to infect previously immune people might be what sets a dangerous VOC apart, says Rambaut. “It’s not that all chronic infections are going to produce VOCs. It’s going to be one in a million.”
That means that surveillance is unlikely to detect a variant at its point of emergence. In a May preprint, researchers spotted an Omicron strain that had picked up other spike mutations during chronic infection in an immunocompromised individual, and showed that it had spread to several people in the same hospital, as well as in the local community. But wider spread of such infections seems exceedingly rare. A February preprint documenting 27 people with chronic infections reports no evidence that any had spread the virus to other individuals. If VOCs so rarely emerge from chronic infections, it will be difficult to prevent them without reducing overall rates of infection around the world, says Adi Stern, an evolutionary virologist at Tel Aviv University in Israel, who led the study.
Nevertheless, there is an urgent need to understand the viral factors that contribute to chronic infections. “We need to go beyond the case reports and understand what the virus is actually evolving during this time,” says Sigal.
Sigal and his team are tracking people with advanced HIV, whose immune systems can be severely compromised, to identify factors associated with chronic SARS-CoV-2 infection. HIV infects immune cells called CD4+ T cells, which also support the production of antibodies against viruses such as SARS-CoV-2. In unpublished work, Sigal and his colleagues have found that low levels of CD4+ T cells are associated with a risk of chronic SARS-CoV-2 infection, and that many of the cases are mild, with few or no respiratory symptoms.
People with compromised immune systems aren’t the only potential source of variants. Researchers have documented SARS-CoV-2 infections lasting multiple weeks in people with healthy immune systems. From the perspective of natural selection, even a relatively short three-week infection provides exponentially more opportunities for the virus to evolve, compared with an acute infection lasting a week, says Martin.
People with relatively healthy immune systems might also provide the virus with more selection pressure than individuals who have impaired immune responses, says Hill. But how to identify people who are susceptible to such infections or what their symptoms might look like is an open question. “I would suspect they’re a lot more common than we realize,” says Hill.
Last year, Gonzalo Bello, a virologist at the Oswaldo Cruz Institute in Rio de Janeiro, Brazil, and his colleagues identified several strains of SARS-CoV-2 circulating in Amazonas state in Brazil. These carried some — but not all — of the mutations found in the Gamma variant that drove the region’s ferocious second wave in 2021. But each of the Gamma-like strains also had their own unique mutations: evidence, Bello says, that Gamma might have evolved not from a single chronic infection, but from transmission chains of medium-length infections involving relatively healthy people.
Such transmission chains could have contributed to the diversity of Omicron lineages, Bello suggests. “Maybe these individuals are where some of the steps in the origin of VOCs are happening,” he says. And if chronic infections in healthy people are a likely source of VOCs, improving global vaccination rates could help to prevent new ones emerging, Hill adds. “When you’ve got these huge uncontrolled waves of infection, you’re sowing the seeds for the next.”
Antiviral drugs and other treatments taken during a chronic infection could also be playing a part in the virus’s evolution. One trait scientists are looking out for is resistance to COVID-19 drugs such as Paxlovid (nirmatrelvir–ritonavir) and molnupiravir. (Resistance to the antiviral remdesivir has already been documented in chronic infections.) The drugs affect highly conserved viral proteins — for which the barrier to drug resistance is high — but evolutionary leaps that characterize chronic infections could buy the virus time to come up with a way around that, says Gupta.
In unpublished laboratory experiments, a team led by virologist David Ho at Columbia University in New York City has found that SARS-CoV-2 can take numerous paths to Paxlovid resistance. Some involve gaining compensatory mutations that allow the virus to overcome the costs of Paxlovid resistance, allowing them to thrive, at least in the lab. Such mutations are unlikely to be behind anecdotal reports of recurring SARS-CoV-2 symptoms after Paxlovid treatment, says Ho (who himself experienced such a rebound). But if the treatment, which is normally taken for five days, is administered for a longer period to treat a chronic infection, there is a good chance resistance will emerge.
There is also an urgent need to identify effective treatments for chronic infections — particularly in people with immune-system impairments, who don’t always mount a strong response to vaccines. Most approved monoclonal antibody drugs are not effective against Omicron and its offshoots, and researchers have shown in a preprint that resistance to these therapies can emerge when they’re used to treat chronic infections.
Convalescent plasma should create a higher evolutionary barrier than monoclonal antibody therapies, says Arturo Casadevall, a microbiologist at John Hopkins Bloomberg School of Public Health in Baltimore, Maryland. Plasma that contains high levels of diverse antibodies has been shown to be effective at treating COVID-19, and some physicians are now giving it to people with compromised immune systems.
Antiretroviral drugs that target HIV can also help people living with that virus to clear chronic SARS-CoV-2 infections, but adherence to the drugs can be a challenge, Sigal notes.
Last October, UK clinicians reported a case in which a person’s chronic infection was cleared after they received a COVID-19 vaccine. For the Austrian woman whom Sonnleitner and her colleagues studied, the end of her seven-month infection also followed vaccination. But it’s impossible to know if the vaccine is what helped her to recover.
That outcome is rare for people with chronic infections, however; many reports end in death. “They really are heartbreaking cases,” Stern says. As many parts of the world attempt to move on from the pandemic, with some healthy people shrugging their shoulders at ‘mild’ Omicron infections, Stern says we must do more to protect those who are most at risk of a chronic SARS-CoV-2 infection. “It’s dangerous for them — and it’s dangerous for us as a society.”
Why Omicron variants BA.4 and BA.5 are causing fresh U.S. outbreaks
More infectious than past strains, these subvariants can also more easily escape antibodies from vaccines and previous infections.
Two Omicron subvariants are now causing more than half of new coronavirus infections in the United States—and both are very good at dodging antibodies in people who have been vaccinated and boosted, as well as in people who had a previous COVID-19 infection.
First spotted by scientists in South Africa in January and February this year, the BA.4 and BA.5 subvariants became dominant in the U.S. in less than two months, according to this week’s estimates from the U.S. Centers for Disease Control and Prevention. For the week ending on June 25, BA.4 accounted for 15.7 percent of new cases, while BA.5 was responsible for 36.6 percent.
“BA.4/BA.5 certainly is more infectious compared to previous Omicron variants,” says Yunlong Richard Cao, an immunologist at the Biomedical Pioneering Innovation Center at Peking University in Beijing, China. Cao’s research shows that one of the most concerning traits of these variants is their ability to evade the immune system and break through herd immunity.
That’s of particular concern because almost a quarter of the eligible U.S. population has not received a vaccine of any kind. And for those who have, even a full dose doesn’t seem to sufficiently block the new variants.
“Two doses do not offer much in terms of protection against BA.4 and BA.5,” says Shan-Lu Liu, a virologist at the Ohio State University in Columbus. A little over half of U.S. adults have received their first booster dose, but more than 30 percent of those over 65 have not, and they are at high risk for COVID-19 infection or reinfection.
Despite this concern, experts stress that vaccines and boosters are not completely ineffective: “Immunity from current vaccines is still expected to provide robust protection against severe disease, hospitalization, and death,” says Dan Barouch, an immunologist at Harvard Medical School in Boston.
How much do these subvariants dodge immunity?
In addition to Cao’s work, multiple studies are showing that BA.4 and BA.5 excel at dodging antibodies.
“Following [even a] third dose of the Pfizer vaccine, BA.4 and BA.5 escaped from vaccine-induced and infection-induced antibodies more effectively than prior Omicron variants,” says Barouch. His research also shows that BA.4 and BA.5 can effectively dodge antibodies created after Omicron breakthrough infections in vaccinated people.
Liu’s research shows that people who received just two doses of either mRNA vaccine did not produce sufficient antibodies to block any Omicron subvariant, including BA.4 and BA.5. While a booster dose significantly improved protection, it was still less efficient against BA.4 and BA.5.
And in a study that is not yet peer reviewed, Alex Sigal, a virologist at the Africa Health Research Institute and at the University of KwaZulu-Natal in Durban, South Africa, found that antibodies from a previous infection with the original Omicron BA.1 strain do not protect against BA.4 and BA.5 infection in either partially vaccinated or unvaccinated people.
What makes BA.4 and BA.5 different?
While BA.4 and BA.5 are almost identical to each other, BA.5 spreads even faster than its “twin” and all other Omicron variants, according to the data from the United Kingdom.
The two variants differ from the Omicron BA.2 subvariant by just six mutations within the spike protein—the part of the SARS-CoV-2 virus that anchors to receptors on human respiratory cells and allows the virus to enter.
Kei Sato, a virologist at the University of Tokyo, has shown that one of these mutations helps the virus anchor to human cells and replicate better.
“It’s quite a useful sort of mutation for the virus,” says Ravindra Gupta, an immunologist and infectious disease specialist at the University of Cambridge in the U.K. Sato and Gupta’s work has shown that this mutation weakens the potency of existing antibodies.
Sato’s unpublished research also indicates that in hamsters, BA.4 and BA.5 target lung tissues more efficiently than previous Omicron variants. But it’s too early to say whether BA.4 and BA.5 can cause more severe diseases in humans, says Olivier Schwartz, a virologist and immunologist at the Pasteur Institute in France.
In South Africa, the surge in infection caused by BA.4 and BA.5 did not lead to as many hospitalizations as the original Omicron wave, says Tulio de Oliveira, a bioinformatician at Stellenbosch University in South Africa who discovered the Omicron variants.
“We do know that it didn’t really drive much of a severity wave in South Africa, which is somewhat reassuring,” says Gupta, “although they’re a much younger population.”
In Portugal, on the other hand, where BA.5 now accounts for almost 90 percent of infections, hospitalization and intensive-care admissions have risen during the past six weeks, mainly among people ages 60 years and older.
What’s next for the vaccines?
Both Moderna and Pfizer have developed new types of “bivalent” boosters that are based on both the Omicron BA.1 subvariant and the original version of SARS-CoV-2 used in the approved shots.
It’s unclear how the updated bivalent booster will fare against BA.4 and BA.5, since both the Moderna and Pfizer boosters generated a weaker antibody response to these subvariants than to BA.1. The U.S. Food and Drug Administration has admitted that the bivalent booster is “already somewhat outdated.”
Regardless, an FDA advisory panel recommended on Tuesday to start using the updated COVID-19 booster shots in the fall.
Along with improvements to the vaccines, preventive strategies such as social distancing, avoiding crowded indoor places, and masking remain very effective at reducing infection risk and decreasing the likelihood that new immunity-evading variants will evolve.
“Waning vaccine immunity and decreased masking are also major contributors to the continued circulation of the virus,” says Barouch.
“We just have to be a bit careful in our daily life,” says Sigal. “COVID-19 is not done.”
Omicron BA.4.6 is slowly rising and Evusheld won’t work, FDA warns
14-day daily average
IN THE LAST TWO WEEKS:
CONFIRMED CASES (-34%)
REPORTED DEATHS (-20%)
Although the Omicron subvariant BA.5 is currently causing most new COVID-19 cases in the United States, a new emerging variant could drive another winter surge, according to White House chief medical adviser, Anthony Fauci.
BA.5 accounts for nearly 81 percent of the genetically sequenced samples collected in the U.S. between September 25 and October 1, but the number of cases caused by another Omicron subvariant called BA.4.6–which is capable of evading immunity from vaccination and previous infection—is steadily rising. It currently accounts for 13 percent of the sequenced samples.
New daily Covid-19 cases
14-day daily average0200,000400,000600,000800,000March 2020AprilMayJuneJulyAug.Sept.Oct.Nov.Dec.Jan. 2021Feb.MarchAprilMayJuneJulyAug.Sept.Oct.Nov.Dec.Jan. 2022Feb.MarchAprilMayJuneJulyAug.Sept.Oct.
Note: Counties recording fewer than five days of confirmed cases and having fewer than 10 cases are not shown.
The growing number of BA.4.6 cases led the U.S. Food and Drug Administration to issue a warning indicating that Evusheld—the only monoclonal antibody authorized for COVID-19 prevention in immunocompromised individuals and people who can’t take the COVID-19 vaccine—may be completely ineffective against subvariants like BA.4.6.
The agency has directed healthcare providers to inform patients using Evusheld about the risks of COVID-19 infection as the BA.4.6 subvariant circulates. The advice is to get tested if symptoms develop and seek medical attention immediately if the COVID-19 test is positive.
Confirmed cases by month
Source: New York Times, Census Bureau
What comes after Omicron? New variants are emerging.
Though they don’t yet have their own Greek names, many variants of SARS-CoV-2 continue to evolve and spread.
Every few months for the first two years of the pandemic the public learned the name of a new coronavirus variant that had emerged and was more adept at infecting us or causing severe disease. Ten variants with Greek names—Alpha through Mu—killed millions. Then in November 2021, Omicron, a vastly different version of the virus emerged. For the past 10 months the World Health Organization hasn’t named any new variants, which begs the question: Has the virus stopped evolving?
At least 300 Americans have died from COVID-19 every day for the past three months and roughly 50,000 new COVID-19 infections were reported in the U.S. every day in September—all caused by new sublineages of Omicron: BA.2, BA.2.12.1, BA.4., and BA.5. Infection rates among U.S. nursing home residents have risen nine-fold since the end of April, and by August death rates almost quadrupled in this group, according to the data compiled by the AARP Public Policy Institute and the Scripps Gerontology Center at Miami University in Ohio. In the United Kingdom, often a harbinger of COVID-19 trends in the U.S., symptomatic infections have steadily increased since August 27—the day they hit lowest level this year—according to the ZOE COVID-19 study, an App-based project in which patients enter their symptoms on their phone. While WHO has not anointed any of these recent Omicron derivatives with a Greek letter of their own, experts fear these variants could undermine the new boosters and treatments, leading to a new wave of infections and deaths.
The coronavirus is continuously evolving and gaining novel mutations; to date there have been more than 200 newer Omicron sublineages and their derivatives. “SARS-CoV-2 evolution is not over,” says Olivier Schwartz, head of the Virus & Immunity Unit at Institut Pasteur, Paris.
Marion Koopmans, the director of the WHO Collaborating Center for emerging infectious diseases and a member of WHO’s mission to probe the origins of the COVID-19 pandemic says, “The situation is much better than it has been.” But she cautions that with fall and winter approaching, we should remain prepared for another substantial wave. “A marathon runner does not slow down before the finish line.”
SARS-CoV-2 variants are still evolving
Every time SARS-CoV-2, the virus that causes COVID-19, replicates during an infection, it can make mistakes and change a little bit. These changes, called mutations, are random and usually have no or little consequence for the virus. If the same mutation appears and spreads in unrelated populations, that suggests it offers an advantage to the virus. Those mutations then create a new branch of the SARS-CoV-2 evolutionary tree. The viruses that make up that branch are called “variants.”
“The more SARS-CoV-2 circulates, the more it may change,” says Maria Van Kerkhove, the epidemiologist who leads the COVID-19 response at WHO. Scientists also believe that Omicron like variants could evolve in people with compromised immune systems where the virus can persist longer while acquiring dozens of new mutations.
Some mutations can help a variant spread more easily or may cause more severe disease. Others can alter the appearance of the virus, enabling it to dodge immunity from previous infections or vaccines and making it more difficult to detect. These mutations can also render authorized therapies ineffective. When this happens, WHO labels the variant as interesting or concerning.
In May 2021, WHO began assigning variants of interest and variants of concern letters of the Greek alphabet. “But WHO does not name all variants,” says Anurag Agrawal, the chair of WHO’s Technical Advisory Group for Virus Evolution which makes recommendations on naming variants. “WHO only names a variant when it is concerned that additional risks are being created that require new public health action,” Agrawal explains.
Currently, all Omicron sublineages are considered variants of concern because they share similar characteristics: They spread more easily than earlier variants and can dodge previous immunity. But fortunately, infection from one Omicron subvariant still sufficiently reduces the risk of getting reinfected with another. The subvariants also don’t seem to pose greater risks that the parent Omicron, says Van Kerkhove.
Omicron variants show evolutionary leaps
The emergence of Omicron less than one year ago represented a big shift in SARS-CoV-2 evolution. More than half of COVID-19 infections worldwide since November 2021 were most likely caused by one of the five Omicron subvariants: BA.1, BA.2, BA.3, BA.4 and BA.5. With Omicron’s ability to dodge immunity from previous variants, it has prompted scientists, including Schwartz, to suggest that Omicron could even be considered a distinct SARS-CoV-2 serotype—a virus that is so different from previous variants that antibodies generated against one do not protect sufficiently against the other. For example, flu virus has three serotypes: influenza A, B, and C.
In the last few months Omicron BA.2 has spawned a series of variants including BA.2.75, BA.2.10.4, BJ.1, and BS.1. These variants, some carrying dozens of new mutations, are so different from parental variant BA.2 that scientists call them “second generation” variants. A second-generation variant represents a large evolutionary jump from previous variant lineages without small intermediate steps.
On the evolutionary scale, the newly spreading variants, such as BA.2.75 are more different from the original Omicron than Alpha, Beta, Gamma, and Delta were from the ancestral strains, says Thomas Peacock, a virologist at Imperial College London. All the mutations in these early variants look minor compared to Omicron and its subvariants, says Peacock.
“One potentially worrisome subvariant is BA.2.75.2, which carries additional mutations compared to BA.2.75 and seems to be particularly resistant to antibodies,” says Schwartz.
While WHO may not have given these new variants a Greek letter name, Yunlong (Richard) Cao, an immunologist at Peking University in Beijing says, “It’s definitely inappropriate to say there have been no new variants since November 2021.”
BA.5 is currently predominant in many countries, and BA.2.75 in others. They are both able to escape the immune systems of people who have been vaccinated and or suffered an infection, although current vaccines may still hold good.
“What we are seeing now is that evolution is continuing,” Koopmans says. This is what you would expect when there is the combination of substantial circulation and greater acquired immunity. “So we do expect further escape variants,” she adds.
There is an ongoing debate about how useful it is to lump all Omicron subvariants together. Although the Omicron lineages BA.1, BA.2, and BA.5 were close enough to be called Omicron, some scientists think that the new variants are distinctive enough that they could be given a new Greek letter name.
“Some of these new viruses are as genetically distinct as the original variants so it remains unclear how helpful it is thinking of them as Omicron still,” Peacock says.
WHO’s task force disagrees. “If any variant or subvariant is determined to be significantly different than other variants or subvariants of Omicron, they will be assigned a new name,” says Van Kerkhove. “But right now, all of these subvariants are considered Omicron, all are variants of concern, and all require enhanced actions in countries.”
As there is no reliable human data to indicate that the new Omicron subvariants are more severe than others, says Agrawal, the public health advice remains the same.
In the meantime, early diagnosis, early clinical care, appropriate use of available therapeutics, and vaccination are needed to reduce the spread of the virus and reduce the chance of new variants emerging, says Van Kerkhove. “We can live with COVID-19 responsibly and take simple measures to reduce the spread, such as distancing, masking, ventilation, cleaning hands, staying home if unwell.”
Surprising Omicron origins study comes under scrutiny
Sequences of early forms of the fast-spreading variant reported to have been circulating in West Africa could have resulted from contamination.
A study that proposes that ancestors of the fast-spreading Omicron coronavirus variant were circulating undetected in Africa for months before the alarm was raised has prompted fierce discussion. The paper, published last week in Science, identifies sequences that the authors say are from Omicron’s predecessors, which they say were spreading from August 2021, some three months before researchers in South Africa and Botswana noted the variant’s arrival in November that year. But many researchers think the sequences are probably the result of contamination in the laboratory.
“I’m somewhat sceptical of this paper,” says Angela Rasmussen, a virologist at the University of Saskatchewan in Saskatoon, Canada. Rasmussen is not convinced that the analysis rules out contamination during sample preparation and sequencing, which is a familiar problem for researchers in the field.
Researchers have been puzzled by Omicron’s emergence. The variant contains a host of unusual mutations that had not been seen before. There are currently three theories for the conditions that could have given rise to Omicron: that it gradually evolved in a part of the world where testing and genomic sequencing is limited; that it spread undetected in animals; and that the mutations accumulated in people with compromised immune systems infected for long periods.
Research over the past year has supported the third theory, but the latest analysis suggests that Omicron could have evolved undetected in western Africa, where sequencing is rare.
As part of the study, labs across 22 African countries analysed more than 13,000 virus samples taken from people who had COVID-19 between mid-2021 and early 2022. These samples had not been sequenced at the time of collection. The team developed a rapid and specific test to identify the BA.1 Omicron subvariant and the Delta variant. “This is a really cool way of doing variant-specific surveillance,” says Joshua Levy, an applied mathematician at Scripps Research in La Jolla, California.
The researchers found that, by the end of December 2021, Omicron had replaced Delta as the dominant variant across Africa, starting in the south and moving up towards the west and east, before taking over in northern Africa.
They also sequenced five virus samples from Benin in West Africa that were collected between 22 August and 27 October 2021, months to weeks before Omicron was first detected. Genomic analysis of the evolutionary relationship between these early sequences and Omicron suggests that they could be its close ancestors.
The early sequences contained some of the mutations that make BA.1 so transmissible, says study co-author Jan Felix Drexler, a virologist at the Charité University hospital in Berlin. They are “snapshots of what the virus looked like when it was getting to Omicron”. Drexler says Omicron probably evolved gradually by spreading from person to person, many of whom might already have developed some immunity to the virus.
But researchers who have reviewed the study and the virus sequences from Benin, which have been posted in a public repository, say that the sequences are probably false positives.
The pattern of evolution observed in the viral samples does not follow a sequential order, which would be expected if the virus gradually evolved over time, says Joel Wertheim, a molecular epidemiologist at the University of California, San Diego. “This doesn’t look like SARS-CoV-2 evolution, it looks like SARS-CoV-2 contamination.”
Another warning signal is that many of the sequences from Benin seem to carry several mutations specific to Delta, says Levy. “It’s very unlikely that these mutations would have popped up in a non-Delta sample.”
To explain some of these observations, researchers say that either the virus had to go through extensive recombination — in which viruses swap chunks of RNA with each other — or the sequences are the result of contamination in the lab. Richard Neher, a computational biologist at the University of Basel in Switzerland, thinks that recombination is unlikely and not consistent with what has been observed in the evolution of SARS-CoV-2 so far.
An alternative explanation that needs further investigation is that samples containing very small amounts of Delta variant were contaminated with Omicron, says Darren Martin, a computational biologist at the University of Cape Town in South Africa.
“I consider this the more likely explanation,” says Neher. “Given how rapidly Omicron spread once it entered the general population, it is unlikely that it had circulated for several months undetected across” Africa.
Drexler says he and his team used several techniques to ensure their sequencing was as robust as possible. He says they are now re-checking their data carefully. “Should there have been a mistake despite all our precautions, we will handle this appropriately, of course.”
Several researchers have requested detailed sequencing data from the paper’s authors, and many are withholding judgement until they have interrogated the raw data. Drexler says they are preparing to upload those data to a public repository.
Ultimately, the study points to the importance of genomic sequencing for tracking infectious diseases. Researchers in South Africa detected Omicron early and this paper highlights the strength of their genomic surveillance, says one of them, Tulio de Oliveira, a bioinformatician at Stellenbosch University’s Centre for Epidemic Response and Innovation, who helped to sound the alarm about Omicron.
Coronavirus in the U.S.: Where cases are growing and declining
In the United States, COVID-19 linked hospitalizations are rising again as highly contagious Omicron subvariants BQ.1.1 and BQ.1 spread rapidly across the country. That upward trend is particularly stark among individuals 70 years of age and older, who are particularly vulnerable because only 32.6 percent of vaccinated senior citizens have received their Omicron-specific booster.
These updated shots weren’t approved for use in kids under age five until yesterday, when the U.S. Food and Drug Administration authorized Omicron-specific boosters for use in younger children.
Note: Counties recording fewer than five days of confirmed cases and having fewer than 10 cases are not shown.
To date, kids between the ages of six months and four years were eligible to receive three shots of Pfizer-BioNTech’s original COVID-19 vaccine as their primary series. As early as next year, however, the companies will replace the third shot with its Omicron-specific one for children who are yet to receive their last dose.
Kids who received the original Moderna vaccine will be eligible to receive its updated version as a booster two months after completing their primary series.
For now, the FDA is urging parents to get their children vaccinated “as it can potentially help protect them from COVID-19 during a time when cases are increasing,” according to the federal agency’s December 8 statement.
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