I have written several articles on the coronavirus and on masks and healthcare issues. A series of links have been provided at the bottom of this article for your convenience. This article will, however address a different aspect of the virus or on healthcare issues in general.
I know COVID has been around a while, so now even my third part is acting very sluggish. So I will start a 5th installment. The previous three sections will remain all accessible for viewing, though they will now function as an archive. https://common-sense-in-america.com/2023/11/08/the-coronavirus-exposed-part-4-more-updates/. I am anticipating that this will most likely be my last installment in quite some time, as the updates are failry infrequent now.
Table of Contents
-COVID-19 can ruin your sleep in many different ways—here’s why
-COVID-19 can interfere with your period in many ways. Here’s how.
-Why does COVID-19 cause brain fog? Scientists may finally have an answer.
COVID-19 can ruin your sleep in many different ways—here’s why
Scientists are learning more about the havoc that viruses and bacteria wreak on sleep. Here’s what you need to know about seeking care for insomnia.
Six weeks after a mild case of COVID-19 early in the pandemic, Erika Thornes started waking up every night between 2 and 3 a.m. Unable to fall back asleep, she would listen to podcasts, read, and scroll through Twitter before finally dozing off by 4 or 5 a.m. Thornes, the mother of three teenagers in San Diego, continued to struggle to sleep through the night for more than two years after that—a pattern that improved only after she started taking a new medication following her second bout with the virus in the summer of 2023.
A similar thing happened to her husband during a COVID-19 infection. He was suddenly waking up at 3 a.m. every night. His sleep improved when he stopped testing positive, but the symptom was extreme while it lasted. “He was quite shocked,” she says. “He knew I was waking up, but I don’t think he quite understood the severity of ‘awake.’”
Nightmares. Days without sleep. Waking in a panic in the middle of the night. Sleeping for 18 hours a day. As COVID-19 swept through the global population, so too did reports of sleep disruptions both during an infection and in the weeks and months beyond.
Studies published since the pandemic began have revealed new details about how the virus altered sleep and have documented the general ways that bacterial and viral infections interfere with sleep through physical and psychological mechanisms. New research has also revealed how poor sleep during and after COVID-19 can exacerbate many symptoms of both acute and long COVID—including brain fog—and how insomnia can lower production of antibodies after vaccination.
Recognizing the potential for SARS-CoV-2—the virus that causes COVID-19—to upset sleep, experts say, can help people get the care they need.
How sleep and the immune system affect each other
Sleep is intricately entwined with the immune system, a link both well-known and still mysterious. Getting enough rest can help prevent infections, according to evidence and observations going back thousands of years. But infections can also disrupt sleep in complicated ways.
Studies in animals show that viruses and bacteria alter both the amount of time spent sleeping and the kind of sleep, says John Axelsson, director of the Sleep Laboratory at Stockholm University’s Stress Research Institute in Sweden. When researchers inject rabbits or rodents with moderate doses of bacteria or viruses, the animals sleep more. They get more non-rapid eye movement sleep, a deep restful state thought to be important for recovery; and they spend less time in dream-filled REM sleep.
Cytokines, a category of molecules that can stimulate or slow down inflammation, appear to play a major role in these patterns, Axelsson says. When healthy animals are sleep deprived, levels of some pro-inflammatory cytokines in the brain rise, causing the animals to sleep more than usual. When scientists block these cytokines, animals don’t sleep more—even when they are sleep deprived.
It’s harder to do the same kind of research in people, and results are mixed about how sleep changes during illnesses. But studies suggest that, at least to some extent, inflammatory molecules affect sleep in ways comparable to other animals. In studies from the 1990s and early 2000s, researcher Thomas Pollmächer and colleagues injected people with bits of bacterial cell walls, called endotoxins, and found that mild activation of the immune system increased the drive for sleep and enhanced non-REM sleep.
But once the immune system revved up with increased cytokine levels and symptoms of illness, people experienced more disrupted sleep, not typically seen in animals. “The inflammatory system increases the drive for sleeping,” Axelsson says. “But at the same time, it then disrupts your sleep if you get a fever.”
To see how respiratory infections affect human sleep, Axelsson and colleagues recruited 100 healthy adults to keep a detailed sleep diary after experiencing the first symptoms of a respiratory infection while wearing a sleep-tracking device on their wrists. Of the 100 volunteers, 28 people got sick. Overall, those people spent longer in bed and slept more after their symptoms began, the researchers reported in 2019.
But this wasn’t a restful sleep. Infected people had difficulty falling asleep, woke up more, and had a more restless sleep especially when they were most symptomatic. As symptoms eased, sleep improved. Anecdotally, that’s the same pattern reported by many people with COVID-19—a lot of sleep initially followed by insomnia or other disruptions while sickest. The physiological drive to sleep more while getting sick might be adaptive—helping the body fight off the invader, Axelsson says.
Why sleep problems continue after COVID infection
For many people, sleep troubles don’t end on Day 10 or when a person tests negative. To gauge how often sleep troubles persist, researchers surveyed more than 650 long COVID patients who visited the Cleveland Clinic’s reCOVer Clinic between February 2021 and April 2022. Up to six months after an infection, 41 percent reported sleep disturbances; an additional 7 percent reported disturbances that were severe. Black patients, 12 percent of study participants, were three times more likely to report sleep problems compared with other groups—echoing disparities seen throughout the pandemic, says Cinthia Peña Orbea, a sleep specialist and lead author of the study, which was published in June.
Elsewhere, there have been reports of post-COVID-19 narcolepsy, excessive sleeping, and physically enacting dreams with movements like kicking and talking instead of lying still with typical sleep-induced paralysis, says Monika Haack, a psychoneuroimmunologist at Harvard Medical School in Boston, who co-authored a 2019 review of the links between sleep and disease.
Peña Orbea’s study suggests that long COVID-19 falls in line with other chronic illnesses for causing sleep issues. About 60 percent of people with HIV and more than 50 percent of people with hepatitis C experience poor sleep as do people with ME/CFS, also called chronic fatigue syndrome. People with inflammatory bowel disease, rheumatoid arthritis, and other inflammation-related diseases—all immune disorders—often suffer from lack of sleep.
Sleep disorders appear to be common after severe cases of COVID-19, according to new evidence. Among survivors who were admitted to the ICU, put on ventilators, or had extreme symptoms like a very low oxygen levels, a third had ongoing sleep disorders after recovering from their illness, found a 2023 review of 16 studies that included more than 10,500 people.
A direct link from insomnia to respiratory illness
Although getting a good night sleep has long been standard advice for staying healthy, there hadn’t been large studies to assess whether insomnia directly boosted the risk of getting sick, says Hanna Ollila, who studies sleep at the University of Helsinki and Massachusetts General Hospital. To fill the gap, she and colleagues turned to two databases containing health records from 558,000 people in Finland and the U.K.
Ollila’s team reported in 2023 that that a prior diagnosis of insomnia increased the later risk of developing an upper respiratory infection, influenza, and COVID-19. For COVID, the data suggested that insomnia made people more susceptible to developing severe illness rather than making them more vulnerable to infection. “The connection between sleep and infections has been a question in many earlier studies,” Ollila says. The new study, she says, helps draw a line from sleep disruption to risk of getting sick.
Again, inflammation appears to help explain the link. In a 2022 study, Haack and colleagues found that disturbing sleep in 24 healthy people led to the production of more molecules that prolonged inflammation and notably, a suppression of molecules that normally stop that inflammation. Even after three full nights of recovery sleep, inflammation persists, emphasizing the need to preserve good sleep in the first place.
Sleeplessness can cause or exacerbate many symptoms associated with both acute COVID and long COVID, including depression, fatigue, and brain fog. Those symptoms in turn can make it hard to sleep. “It’s always bi-directional,” Haack says. Insomnia, sleep apnea, and other disruptions, she says, “all can lower sleep quality, depth, continuity, or regularity, and dampen the immune supporting functions that come with normal sleep.”
Sleep is also important to get maximum benefits from vaccines, says Nikolaos Athanasiou, a pulmonologist at the University of Athens, Greece. Among 544 healthcare workers who hadn’t previously been infected with the SARS-CoV-2 virus, those with insomnia produced lower levels of antibodies in response to the COVID-19 vaccine. “It has not been pointed out enough,” Athanasious says, “that sleep deprivation and reduced sleep duration decreases immune response.”
Developing drugs for COVID-related sleep disorders?
Ultimately, scientists might be able to develop medications that affect levels of cytokines to improve sleep, says James Krueger, an expert on the biochemistry of sleep at Washington State University in Spokane. But it’s a challenging task because the relationship between cytokines and sleep are extraordinarily complex. Some pro-inflammatory cytokines enhance sleep at low concentrations but at higher concentrations, they lead to wakefulness and fragmented sleep. There are also anti-inflammatory cytokines that mostly inhibit sleep at low concentrations.
Hundreds of proteins interact to regulate the immune system and other processes, Krueger says. COVID-19 and other infections tweak those interactions. Targeting those molecules remains a work in progress. “For complex behaviors and brain processes such as sleep, some new drugs have been developed over the past few years,” he says. “Time will tell if they are better than prior drugs.”
The impact of psychological stress
A better understanding of how infections affect sleep in biological ways will develop with more trials and better data, Axellson says. In the meantime, a slew of studies suggests that stress, disruption in routines, mental health, and other non-physiological factors related to illness also affect sleep.
During lockdowns, 57 percent of people reported poor sleep quality, found a 2020 survey by Italian researchers. Overall, people spent a longer time in bed while quarantined, studies show. But they didn’t sleep as well as before they were confined to their homes and isolated from others, and their dreams became more vivid, bizarre, and emotionally intense.
For many people, those issues persisted even after lockdowns ended, as people started getting out more and feeling less stressed, Italian researchers reported in 2021. The researchers speculated that for many people—including children—psychological distress lingered past the acute phase of the pandemic. A 2023 study by researchers in Spain found that sleep quality declined during lockdowns among kids, ages 5 to 9. Like adults, their sleep hasn’t bounced back since, possibly because of ongoing anxiety and a persistent increase in screen time.
How to improve sleep after COVID-19
Helping people get better rest during and after COVID-19 infections begins with acknowledging the importance of sleep, Haack says. That can include avoiding medications that disturb sleep, such as opioids, and reducing light, noise, and repeated wakeups for people who are hospitalized.
Establishing regular sleep routines with consistent bedtimes and wakeup times are often a part of insomnia care, Axelsson says. It can also help for people to restrict time in bed to increase sleep efficiency and avoid excessive time spent lying awake.
Haack recommends mindfulness apps to reduce stress and anxiety. For her long COVID-19 patients, Peña Orbea has seen cognitive behavioral therapy led to improvements. “With insomnia, the brain is in a hyper-arousal state,” she says. “We try to reset that arousal state of mind.”
Physical activity and being outside in daylight can help a subset of people who may have stopped going out because of their illness, Axelsson says. But for many with long COVID, exercise can cause serious setbacks, underscoring the need for individualized medical care if sleep problems persist post-COVID.
“Sleep disruption can be quite normal during the acute COVID infection, due to sleep-disrupting symptoms such as pain, coughing, stuffy nose,” Haack says. “If sleep disturbances continue to stay beyond the acute symptomatic phase or start to develop as a new symptom, that is the time to seek help.”
COVID-19 can interfere with your period in many ways. Here’s how.
There could be temporary disruptions to your cycle after the vaccine—or more significant issues after a severe bout of COVID-19.
Raven La Fae, a 32-year-old artist in Calgary, Canada, has always been able to predict their menstrual periods almost to the day; it arrived every 28 days and lasted for five. But after contracting COVID-19 in late 2020, that’s no longer the case.
La Fae’s bout with the disease lasted for two miserable weeks. A menstrual cycle landed expectedly during that time, but what was shocking to them was how long the bleeding continued—10 days.
“My period has been funky ever since,” La Fae laments, and after another round of COVID-19 it became even less predictable. While the days between cycles have mostly returned to baseline, the number of days of bleeding have not, lasting up to 10 days a month.
From the beginning of the pandemic, women worldwide noticed changes to their menstrual cycles. In some cases, this happened after contracting the virus; in others, after receiving a vaccine. With so many people recording their cycles in period-tracking apps, researchers have been able to document the phenomenon.
Initially, many physicians were taken off guard. La Fae’s healthcare provider, after determining hormone levels were normal, said she couldn’t explain it. People complained their doctors dismissed their hunch the virus might be linked to disrupted cycles.
“When COVID started we were worried about people dying, so other things were overlooked,” admits Hugh Taylor, chair of obstetrics and gynecology at Yale Medicine. In retrospect, Taylor says, patients should have been alerted to this possibility. “We see irregular menstrual cycles with other acute infections, so it isn’t surprising it happens here.”
Without research or reassurance from physicians, women were alarmed by the deviations in their periods, Taylor says, and for good reason: “We’ve been warning people for years that changes in a period might be a symptom of a hormonal imbalance, or even cancer.”
When girls and women noticed unexpected shifts in their cycle after receiving a COVID-19 shot, some second-guessed their decision to get a vaccine, says Candace Tingen, a program director at the National Institute of Child Health and Human Development, which awarded $1.67 million to five research institutions to study the issue.
Tingen points out that her institute has long emphasized the importance of menstrual cycles to health. “We talk about it as a fifth vital sign,” she says (the other four being body temperature, blood pressure, pulse, and respiration).
Most concerning to younger women was whether these changes could reduce fertility, Taylor says.
It wasn’t until early 2022—two years into the pandemic—that a study of 2,000 American couples published in the American Journal of Epidemiology resolved the question. Women trying to conceive who’d had the virus saw no decrease in fertility. Similarly, the COVID shot had no impact on conception rates.
Both virus and vaccine may temporarily alter menstruation
Several NIH-funded studies have confirmed that COVID does alters cycle lengths in many women, albeit only briefly.
Thousands of reproductive-age women using a period tracking app reported that the time between their periods expanded by more than a day in the month following infection or vaccination, which for most returned to normal the following cycle, researchers reported in August.
Another study of 127 women of childbearing-age in Arizona who had contracted COVID found 16 percent reported some alteration; most common were irregular cycles or longer gaps between bleeds. These shifts were more likely in those whose infection involved more symptoms or was more severe (but not to the point of hospitalization).
Women in this study also had increases in the premenstrual syndrome symptoms of mood changes and fatigue.
“We think of the menstrual period as an acute event that occurs for a few days, but hormones are changing throughout the entire cycle,” explains Leslie Farland, an epidemiology professor at the University of Arizona and the study’s principal investigator.
A large study published in June focused on COVID vaccinations confirmed that here too the number of days between periods increases by about a day during the month of vaccination, but returns to normal after.
That aligns with a prior study tracking 4,000 U.S. women who used one period tracking app and found that, for the vast majority of women, cycles shifted slightly and temporarily; however, the length of bleeding didn’t change, says Alison Edelman, an obstetrician and gynecologist at Oregon Health and Science University and the study’s principal investigator. A second study by Edelman, of nearly 20,000 women in North America and Europe using the same app reported similar findings.
Still, ten percent of the women in Edelman’s study saw their period shift by more than a week after getting the shot. However, these women were also largely back to normal the following month.
None of these studies explain situations like La Fae’s, where menstrual cycles are changed significantly and persistently.
How does coronavirus change a period?
Exactly how the coronavirus or vaccine affects the menstrual cycle isn’t clear.
One hypothesis posits that COVID-19 may affect what’s known as the hypothalamic-pituitary-ovarian axis. To begin each monthly cycle, the hypothalamus gland signals the pituitary gland to secrete two hormones that together release an egg from the ovaries.
It’s possible the coronavirus affects the hypothalamus directly, Taylor says, but the body may also proactively decrease the activity of these glands if the virus is detected. “This has evolutionary advantages, because you don’t want to get pregnant when you’re fighting off a physical stressor, which could be an illness or malnutrition or the like,” he explains.
Alternatively, the immune system engaged in fighting the virus could alter the normal inflammatory response of the uterine lining (endometrium) during the cycle.This may be why people who experienced a more intense bout of COVID—indicating a higher viral load and more immune activity—have higher rates of menstrual changes, as the University of Arizona study found.
That was the case for Annette Gillaspie, a 41-year-old registered nurse in Hillsboro, Oregon, who contracted COVID in 2020 and was extremely ill for more than two weeks. She has since experienced long COVID symptoms, including a fluctuating heart rate and fatigue so extreme a shower can send her to bed for days. Her periods are unusually long and heavy—gushing for almost two weeks some months—and even having a hormonal intrauterine device inserted didn’t reduce the bleeding as it normally does. At some point, she says, she’ll likely have to undergo a hysterectomy.
Vaccines trigger more minor shifts
Vaccines trigger the body’s immune system response, albeit a smaller one than the disease, so the same mechanisms could be involved in their temporary menstrual cycle disruptions, Tingen says.
Disseminating this reassuring information to women so they know to expect this possible side effect is an important public health task, Tingen says.
Anyone whose cycle remains significantly altered for several months, however, should check with their healthcare provider, Taylor says. “My suspicion is that people on the cusp of a medical condition—thyroid abnormalities, hormonal irregularities, bleeding from fibroids—might be pushed over the edge” by the coronavirus or COVID vaccine.
Edelman hopes this will be a teaching moment for her profession. “Menstrual health has been woefully understudied, not just in vaccine trials but in almost every area of research,” she says. “Yet half the population will, does, or has menstruated, and this routine biological function has meaning for the individual and for science.”
Why does COVID-19 cause brain fog? Scientists may finally have an answer.
Nearly 40 percent of long COVID patients suffer from the disorienting condition. Destroyed connections between brain cells may be to blame.
When scientists infected brain organoids—pinhead-size bits of brain tissue grown in the lab—with the virus that causes COVID, they found that not only does it spread in neurons in the brain, it also accelerates the destruction of connections between neurons—called synapses—that are essential for communication.
These discoveries expand understanding of how SARS-CoV-2 can damage the nervous system. COVID-19 patients continue to suffer with a range of symptoms, especially neural and behavioral problems, long after the infection. One such condition, commonly known as brain fog, causes disorientation, memory loss, chronic headache, and numbness, and it affects nearly 40 percent of long COVID patients.
“There are many case reports, even some in our own clinic, of patients who have symptoms [of brain fog] lasting upwards of a year,” says Ayush Batra, a neurologist at Northwestern University Feinberg School of Medicine.
Carl Sellgren, a psychiatrist and cellular biologist, and his team at the Karolinska Institute in Sweden used organoids to study what SARS-CoV-2 does to brain.
“It was quite striking that very small amounts of the virus could quite rapidly spread in the organoids and eliminate an excessive number of synapses,” says Ana Osório Oliveira, a neuroscientist in Sellgren’s team.
Another study found that spike protein—which coats the outer surface of the virus—directly eliminates synapses causing loss of memory in lab mice by causing inflammation.
Destroying too many connections between neurons, or over-pruning, may be causing brain fog in long COVID patients. “This could be one of the many reasons—probably—why we are observing a range of neurological symptoms, even after the infection is long gone,” says Samudyata, a postdoctoral researcher at Karolinska Institute who led the study and only uses one name.
Virus has been found in autopsied brain tissues and throughout the bodies of patients, who died more than 200 days after contracting COVID-19. It is evidence that the virus is capable of persisting in organs throughout the body.
“There are some persistent virus reservoirs that can cause a chronic inflammatory response or autoimmune attack on the brain, which can cause pruning and brain shrinkage,” says Batra.
Pruning connections between neurons is essential for learning
The brain is made of a dense and dynamic network of nerve cells that communicate through synapses that change as humans learn. “Synapses are essentially how cells talk to each other and how information is passed from one part of the brain to another,” Lancaster says.
Synapses are responsible for all the functions of the brain, from memory to controlling movement to feeling emotions, and they are constantly remodeled. “That’s how we learn,” she says.
The junctions between neurons that talk to each other frequently have more knob-shaped synapses that produce neurotransmitters—chemicals that transmit signals to other neurons. Conversely, neurons that communicate less or not at all have fewer synapses because they are removed, or pruned, by immune cells called microglia. Microglia make up to 17 percent of the cell population in some parts of the human brain and perform housekeeping duties by migrating through the brain eating dead cells and scavenging weak synapses.
Although synaptic pruning is most active in developing brains such as in fetuses and infants, it continues in healthy brains throughout life and is necessary for encoding new memories and erasing the ones it no longer needs. Synaptic pruning is also critical for the brain to recover from an injury; allowing it to strengthen synapses which relearn the lost skills and remove synapses that no longer function.
Using brain organoids to study neural damage
Studying a direct link between COVID-19 and cognitive dysfunction, such as brain fog, is difficult in living brains. That is why studies are often limited to cadavers of COVID-19 patients. But brain organoids, often called mini-brains, allow scientists to see in real time how SARS-CoV-2 affects living tissue.
Mini-brains can be used to study infection because scientists can control the amount of viruses that are exposed to individual cells, says Oliver Harschnitz, group leader in the Neurogenomics Research Centre at Human Technopole Institute in Milan, Italy, even though tissue organization is less structured than real brains.
Using brain organoids, Oliveira and her colleagues found that the virus itself was not directly pruning the synaptic connections but was activating the microglia.
“We found that following infection by SARS-CoV-2, somehow the microglia become immunoreactive, and eat more of the synapses than normal,” Samudyata says.
It’s a very interesting study because it really shows the quantitative differences in the microglial activity after COVID-19 and its effect on synapses says Ayush Batra, a neurologist at Northwestern University Feinberg School of Medicine.
Too much synapse pruning can be detrimental and has been linked to neurodevelopmental disorders such as schizophrenia, as well as neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.
In a follow-up study, Sellgren’s team has found that a protein called C4A—which helps remove microbes and infected cells—also tags synapses for removal. Although his research doesn’t directly connect C4A with brain fog, it suggests that inflammation after infection can affect pruning of synapse, depending on genetics, says Sellgren.
If the excessive elimination of synapses that occur in brain organoids after SARS-CoV-2 infection also occurs in people, it may destroy vital connections and explain why some with COVID-19 suffer from long-term neurological symptoms.
“Too much synapse elimination would be expected to affect a person’s ability to form new memories, or to remember existing ones, and could help explain the sluggish brain functions seen in brain fog,” Lancaster says.
This is consistent with studies done at the U.S. National Institutes of Health that have found antibodies produced in response to SARS-CoV-2 can attack the cells lining the brain’s blood vessels, causing damage and inflammation—which activates microglia—even if the virus doesn’t directly enter the brain. That may explain why, as Batra’s team has shown, some long COVID patients not sick enough to be hospitalized continue to experience neurologic symptoms beyond a year after initial infection.
Is the loss of synapses causing brain shrinkage?
A U.K. study has also shown that even mild COVID-19 can shrink the brain through loss of gray matter—the outermost layer of the brain that is vital for controlling movement, memory, and emotions—causing physical changes equivalent to a decade of aging. A new study, which has not yet been peer-reviewed, suggests that COVID-19 can accelerate the decline of cognitive ability equivalent to ten years of normal aging, especially after severe COVID disease or severe long COVID.
“We are still unclear what may contribute, in general, to a loss of gray matter volume or thickness observed using MRI,” says Gwenaëlle Douaud, a neuroscientist at the University of Oxford who led the study.
While synapse elimination, as shown in Samudyata’s study, could account for a small percentage of the change in the gray matter, says Douaud, more studies combining imaging with tissue sections are required to determine the other factors that lead to brain shrinkage.
Hyperactive microglia may cause problems in other ways. The Swedish study also shows that the pattern of genes turned on and off by the microglia in brain organoids after SARS-CoV-2 infection mimicked gene activity seen in neurodegenerative disorders. This may explain why there is a three times higher risk of developing neurological or psychiatric conditions within six months after COVID-19 compared with those who were not infected. In adults aged over 65, the risk of developing dementia after a COVID-19 infection is almost twice that of other respiratory infections.
However, scientists caution that much more research is needed to understand the effect of SARS-CoV-2 infection on the brain. As organoids resemble immature cells—like those in a fetal or post-natal state—this limits extrapolation of the results to mature adult brain cells.
“While these data are exciting and indicate a role for proinflammatory microglia in the disease mechanisms underlying long COVID, more studies are required to validate these findings and build on them,” Harschnitz says.
It’s also not known how long COVID affects quality of health and whether it has long term or irreversible effects on the brain. So as the pace of holiday and indoor winter activities picks up, Samudyata advises taking preventative measures and staying up to date on vaccinations to minimize the chance of getting COVID over and over. While it isn’t clear how the virus exerts detrimental effects on the brain, it’s evident that it does cause damage.
nationalgeographic.com, “COVID-19 can ruin your sleep in many different ways—here’s why.” By Emily Sohn; nationalgeographic.com, “COVID-19 can interfere with your period in many ways. Here’s how.” By Meryl Davids Landau; nationalgeographic.com, “Why does COVID-19 cause brain fog? Scientists may finally have an answer.” By Sanjay Mishra;
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