Virus World

If you've had COVID-19, it may still be messing with your brain. Those who have been infected with the virus are at increased risk of developing a range of neurological conditions in the first year after the infection, new research shows. Such complications include strokes, cognitive and memory problems, depression, anxiety and migraine headaches, according to a comprehensive analysis of federal health data by researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care system. Additionally, the post-COVID brain is associated with movement disorders, from tremors and involuntary muscle contractions to epileptic seizures, hearing and vision abnormalities, and balance and coordination difficulties as well as other symptoms similar to what is experienced with Parkinson's disease. The findings are published Sept. 22 in Nature Medicine.  Overall, COVID-19 has contributed to more than 40 million new cases of neurological disorders worldwide, Al-Aly said. Other than having a COVID infection, specific risk factors for long-term neurological problems are scarce. "We're seeing brain problems in previously healthy individuals and those who have had mild infections," Al-Aly said. "It doesn't matter if you are young or old, female or male, or what your race is. It doesn't matter if you smoked or not, or if you had other unhealthy habits or conditions." 

Few people in the study were vaccinated for COVID-19 because the vaccines were not yet widely available during the time span of the study, from March 2020 through early January 2021. The data also predates delta, omicron and other COVID variants. A previous study in Nature Medicine led by Al-Aly found that vaccines slightly reduce -; by about 20% -; the risk of long-term brain problems. "It is definitely important to get vaccinated but also important to understand that they do not offer complete protection against these long-term neurologic disorders," Al-Aly said. The researchers analyzed about 14 million de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation's largest integrated health-care system. Patients included all ages, races and sexes. They created a controlled data set of 154,000 people who had tested positive for COVID-19 sometime from March 1, 2020, through Jan. 15, 2021, and who had survived the first 30 days after infection. Statistical modeling was used to compare neurological outcomes in the COVID-19 data set with two other groups of people not infected with the virus: a control group of more than 5.6 million patients who did not have COVID-19 during the same time frame; and a control group of more than 5.8 million people from March 2018 to December 31, 2019, long before the virus infected and killed millions across the globe.

The researchers examined brain health over a year-long period. Neurological conditions occurred in 7% more people with COVID-19 compared with those who had not been infected with the virus. Extrapolating this percentage based on the number of COVID-19 cases in the U.S., that translates to roughly 6.6 million people who have suffered brain impairments associated with the virus. Memory problems -; colloquially called brain fog -; are one of the most common brain-related, long-COVID symptoms. Compared with those in the control groups, people who contracted the virus were at a 77% increased risk of developing memory problems. "These problems resolve in some people but persist in many others," Al-Aly said. "At this point, the proportion of people who get better versus those with long-lasting problems is unknown." Interestingly, the researchers noted an increased risk of Alzheimer's disease among those infected with the virus. There were two more cases of Alzheimer's per 1,000 people with COVID-19 compared with the control groups. "It's unlikely that someone who has had COVID-19 will just get Alzheimer's out of the blue," Al-Aly said. "Alzheimer's takes years to manifest. But what we suspect is happening is that people who have a predisposition to Alzheimer's may be pushed over the edge by COVID, meaning they're on a faster track to develop the disease. It's rare but concerning." Also compared to the control groups, people who had the virus were 50% more likely to suffer from an ischemic stroke, which strikes when a blood clot or other obstruction blocks an artery's ability to supply blood and oxygen to the brain. Ischemic strokes account for the majority of all strokes, and can lead to difficulty speaking, cognitive confusion, vision problems, the loss of feeling on one side of the body, permanent brain damage, paralysis and death.

"There have been several studies by other researchers that have shown, in mice and humans, that SARS-CoV-2 can attack the lining of the blood vessels and then then trigger a stroke or seizure," Al-Aly said. "It helps explain how someone with no risk factors could suddenly have a stroke." Overall, compared to the uninfected, people who had COVID-19 were 80% more likely to suffer from epilepsy or seizures, 43% more likely to develop mental health disorders such as anxiety or depression, 35% more likely to experience mild to severe headaches, and 42% more likely to encounter movement disorders. The latter includes involuntary muscle contractions, tremors and other Parkinson's-like symptoms. COVID-19 sufferers were also 30% more likely to have eye problems such as blurred vision, dryness and retinal inflammation; and they were 22% more likely to develop hearing abnormalities such as tinnitus, or ringing in the ears. "Our study adds to this growing body of evidence by providing a comprehensive account of the neurologic consequences of COVID-19 one year after infection," Al-Aly said. Long COVID's effects on the brain and other systems emphasize the need for governments and health systems to develop policy, and public health and prevention strategies to manage the ongoing pandemic and devise plans for a post-COVID world, Al-Aly said. "Given the colossal scale of the pandemic, meeting these challenges requires urgent and coordinated -; but, so far, absent -; global, national and regional response strategies," he said.

Cited research published in Nature Medicine (Sept. 22, 2022):

https://doi.org/10.1038/s41591-022-02001-z 

Fluvoxamine is both inexpensive and highly effective at preventing mild COVID-19 from turning severe.  A cheap, widely available drug used to treat mental illness cuts both the risk of death from COVID-19 and the need for people with the disease to receive intensive medical care, according to clinical-trial results1. The drug, called fluvoxamine, is taken for conditions including depression and obsessive–compulsive disorder. But it is also known to dampen immune responses and temper tissue damage, and researchers credit these properties for its success in the recent trial. Among study participants who took the drug as directed and did so in the early stages of the disease, COVID-19-related deaths fell by roughly 90% and the need for intensive COVID-19-related medical care fell by roughly 65%. “A major victory for drug repurposing!” Vikas Sukhatme at Emory University School of Medicine in Atlanta, Georgia, who studies drug repurposing, wrote in an e-mail to Nature. “Fluvoxamine treatment should be adopted for those at high risk for deterioration who are not vaccinated or cannot receive monoclonal antibodies.”  Study co-author Angela Reiersen, a psychiatrist at Washington University School of Medicine in St. Louis, Missouri, has long been interested in using fluvoxamine to treat a rare genetic condition. While monitoring the fluvoxamine literature before the pandemic, she came across a 2019 study showing that fluvoxamine reduced inflammation in mice with sepsis2. When COVID-19 hit, “I immediately thought back to that paper with the mice,” she says. Reiersen and her colleagues partnered with the organizers of the TOGETHER Trial, which aims to identify approved drugs that can be repurposed to treat COVID-19.

The team’s study included 1,497 people in Brazil who had COVID-19 and were at high risk of severe disease. Roughly half received fluvoxamine, and the rest received a placebo. The trial’s results, published on 27 October, mean that fluvoxamine is one of a handful of therapies that show strong evidence of preventing progression from mild to severe COVID-19. The only early-stage treatments currently recommended by the US National Institutes of Health are monoclonal antibodies, which are costly and difficult to administer in an outpatient setting. Experts are excited about the results, but stress that there are caveats. “We don’t know how applicable this would be in a setting outside of Brazil,” said infectious-disease specialist Paul Sax at Brigham and Women’s Hospital in Boston, Massachusetts. And infectious disease specialist Taison Bell at the University of Virginia in Charlottesville questions how the authors define severe COVID-19, which factors into the assessment of fluvoxamine’s efficacy. The team examined whether people needed more than six hours of treatment in an emergency setting, rather than using the more common metric of hospitalization. Reiersen says the six-hour metric reflects Brazil’s approach to managing COVID-19, in which care is delivered not in hospitals but in COVID-19-specific emergency treatment centres that provide both inpatient and outpatient services.

A COVID drug for the people?

Fluvoxamine’s low cost could make it accessible worldwide, says study co-author Edward Mills, a health researcher at McMaster University in Hamilton, Canada. A ten-day course costs only about US$4, and the drug’s patents have expired, meaning that any company can produce it. “I’ve worked a lot in Africa, for example, where four dollars is a manageable cost,” Mills says. It’s possible that pairing fluvoxamine with a drug that interferes with viral replication, such as Merck’s upcoming antiviral molnupiravir, could be even more effective, Mills says. “It would be fascinating to look at whether or not the antiviral and [anti-inflammatory drugs combined] give you much greater treatment benefits than either alone.”

Results of the clinical trial published in The Lancet Gobal Health (Oct. 27, 2021):

 https://doi.org/10.1016/S2214-109X(21)00448-4 

Anxiety disorders, depression, and insomnia were the most common disorders reported after people developed the disease. People across the world have been experiencing a higher level of stress due to the pandemic, but researchers at the University of Oxford have found the link between COVID-19 and mental illness may be more direct than initially thought. A study published in The Lancet found one in five people diagnosed with COVID-19 developed some form of mental illness 90 days after being diagnosed with the disease caused by the novel coronavirus. The patients had not had mental health disorders prior to contracting the coronavirus.  The study analyzed data from 69 million people in the United States, 62,000 of whom were COVID-19 patients. Anxiety disorders, depression, and insomnia were the most common disorders reported after people developed the disease. 

The virus attacks the central nervous system

The authors of the study said they were unsure why the virus would increase mental health problems in people with otherwise no history of mental illness, and that more research is needed.Simon Wessely, a psychiatry professor at King's College London who was not involved in the study, told Reuters the link between mental health and COVID-19 might be explained by how COVID-19 attacks the central nervous system.  Michael Bloomfield, a consultant psychiatrist at University College London, added the effects of the coronavirus coupled with the external stress of the pandemic might be why this correlation between COVID-19 and mental illness exists. "This is likely due to a combination of the psychological stressors associated with this particular pandemic and the physical effects of the illness," Bloomfield told Reuters. 

Previous research found COVID-19 can lead to lasting cognitive effects 

Mental health consequences aren't the only neurological symptoms exhibited by COVID-19 patients. A study published in the Annals of Clinical and Translational Neurology in October found 80% of people hospitalized with COVID-19 had neurological symptoms like muscle aches, dizziness, and confusion. It also found one-third of COVID-19 patients sustained encephalopathy, a broad term for damage to the brain.  The study published in The Lancet found that in addition to mental illness, people over the age of 65 who developed COVID-19 were more likely to receive their first diagnosis of dementia, a neurological disorder, within 90 days. 

People with previous mental illness were 65% more likely to develop COVID-19

The study authors said they were also surprised to find how vulnerable mental illness made people to contracting COVID-19. People who had mental health conditions prior to the pandemic were 65% more likely to develop COVID-19.  "This is important when we think of the people at risk which should receive the vaccine first. It might be that a history of mental illness should be considered in this decision," Dr. Maxime Taquet, lead author of the study, told Insider. 

Study cited published in The Lancet (Nov. 9, 2020):

https://doi.org/10.1016/S2215-0366(20)30462-4

If you suffer from anxiety, depression or loneliness or feel stressed or worry frequently about Covid-19, you may be at higher risk of developing long Covid, a new study found. You may have up to a 50% higher risk of developing long Covid-19 if you suffer from common psychiatric issues such as anxiety or depression. Signs of the malady can include breathing problems, brain fog, chronic coughing, changes in taste and smell, overwhelming fatigue, difficulties in performing daily life functions, and disruptions in sleep that can last months, even years, after the infection has cleared the body.  People who self-identified as having anxiety, depression or loneliness, or who felt extremely stressed or worried frequently about the coronavirus were more likely to experience long Covid-19, according to the study published this month in JAMA Psychiatry. "We found participants with two or more types of psychological distress before infection had a 50% higher risk of getting long Covid," said study coauthor Dr. Siwen Wang, a research fellow in the department of nutrition at the Harvard T.H. Chan School of Public Health in Boston. 

About 40 million adults over 18 in the United States live with an anxiety disorder, while over 21 million have suffered from major depression, according to national statistics. Many mental health conditions often overlap, with concurrent diagnoses, experts say. More than a fifth of adults in the US (22%) and the UK (23%) say they often or always feel lonely, a Kaiser Family Foundation study said. "Having higher levels of psychological distress prior to a Covid infection also increased the risk of getting long Covid by 50%," Wang said. "Those people also reported more symptoms seen in long Covid."  Instead, the study's message should be that people with existing psychological distress are closer to the "disaster" of long Covid, said Ely, codirector of Vanderbilt's Critical Illness, Brain Dysfunction and Survivorship Center. "Imagine 10 people are running a race, and you give five people a head start," Ely said. "Those are the people who already had a mental health issue -- they are just closer to the unfortunate finish line of getting long Covid."

Cases of major depressive disorder and anxiety disorders increased by more than a quarter worldwide in 2020 due to the COVID-19 pandemic, according to the first global estimates of impacts of the pandemic on mental health, published in The Lancet. In 2020, cases of major depressive disorder and anxiety disorders increased by 28% and 26%, respectively. Women were affected more than men, and younger people were more affected than older age groups. Countries with high COVID-19 infection rates and major reductions in the movement of people—a consequence of measures such as lockdowns and school closures—had the greatest increases in prevalence of major depressive disorder and anxiety disorders. Even before the COVID-19 pandemic, major depressive disorder and anxiety disorders—which can increase the risk of other health outcomes such as suicide—were major contributors to the global burden of disease, affecting millions of men and women of all ages around the world. Lead author Dr. Damian Santomauro, of the Queensland Centre for Mental Health Research, School of Public Health, University of Queensland, Australia, said: "Our findings highlight an urgent need to strengthen mental health systems in order to address the growing burden of major depressive disorder and anxiety disorders worldwide. Promoting mental wellbeing, targeting factors contributing to poor mental health that have been made worse by the pandemic, and improving treatment for those who develop a mental disorder should be central to efforts to improve support services. Even before the pandemic, mental health-care systems in most countries have historically been under-resourced and disorganised in their service delivery. Meeting the added demand for mental health services due to COVID-19 will be challenging, but taking no action should not be an option."  Until now, no studies had analysed the global impact of the COVID-19 pandemic on prevalence of major depressive disorder and anxiety disorders in 2020. Most previous work consisted of surveys in specific locations over a short time period. The new study is the first to assess global impacts of the pandemic on major depressive disorder and anxiety disorders, quantifying the prevalence and burden of the disorders by age, sex, and location in 204 countries and territories in 2020.

A systematic literature review was performed to identify population survey data published between January 1, 2020, and January 29, 2021. Eligible studies reported prevalence of depressive or anxiety disorders that were representative of the general population and had a pre-pandemic baseline. Using a disease modelling meta-analysis tool, data from eligible studies was used to estimate changes in prevalence of major depressive disorder and anxiety disorders due to COVID-19 based on age, sex, and location, including in locations for which no eligible studies were available. Estimates of daily COVID-19 infection rate and movement of people were used as indicators of the impact of the pandemic on populations. The systematic review identified 5,683 unique data sources, of which 48 (one of which reported across two regions) met inclusion criteria. Most studies were from Western Europe (22) and high-income North America (14), with others from Australasia (5), high-income Asia Pacific (5), East Asia (2), and central Europe (1). The meta-analysis indicates that increased COVID-19 infection rate and reduced movement of people were associated with increased prevalence of major depressive disorder and anxiety disorders, suggesting that countries hit hardest by the pandemic in 2020 had the greatest increases in prevalence of the disorders. In the absence of the pandemic, model estimates suggest there would have been 193 million cases of major depressive disorder (2,471 cases per 100,000 population) globally in 2020. However, the analysis shows there were 246 million cases (3,153 per 100,000), an increase of 28% (an additional 53 million cases). More than 35 million of the additional cases were in women, compared with close to 18 million in men.

Model estimates suggest there would have been 298 million cases of anxiety disorders (3,825 per 100,000 population) globally in 2020 had the pandemic not happened. The analysis indicates there were in fact an estimated 374 million cases (4,802 per 100,000) during 2020, an increase of 26% (an additional 76 million cases). Almost 52 million of the additional cases were in women, compared with around 24 million in men. Younger people were more affected by major depressive disorder and anxiety disorders in 2020 than older age groups. The additional prevalence of these disorders peaked among those aged 20-24 years (1,118 additional cases of major depressive disorder per 100,000 and 1,331 additional cases of anxiety disorders per 100,000) and declined with increasing age. Co-author Alize Ferrari, GBD mental disorders team lead at the Queensland Centre for Mental Health Research, School of Public Health, University of Queensland, Australia, said: "The COVID-19 pandemic has exacerbated many existing inequalities, and social determinants of mental health. Sadly, for numerous reasons, women were always more likely to be worse affected by the social and economic consequences of the pandemic. Additional caring and household responsibilities tend to fall on women, and because women are more likely to be victims of domestic violence, which increased at various stages of the pandemic. "School closures and wider restrictions limiting young people's ability to learn and interact with their peers, combined with the increased risk of unemployment, also meant that young people were also more heavily impacted by major depressive disorder and anxiety disorders during the pandemic. It is crucial that policymakers take underlying factors such as these into account as part of measures to strengthen mental health services."

The authors acknowledge that their study was limited by a lack of high quality data on the effects of COVID-19 pandemic on mental health in many parts of the world, particularly low- and middle-income countries. As a result, they say extrapolated estimates generated for countries where data was lacking should be interpreted with caution, and call for improved data coverage and quality globally. Most available data was based on self-reported symptom scales that only estimate probable cases of major depressive disorder and anxiety disorders. More data from diagnostic mental health surveys representative of the general population—of which only three covered the study period—will improve understanding of the pandemic's effects on mental health. The prevalence of other mental disorders—such as eating disorders—might also have been affected by the COVID-19 pandemic, and the authors say these should be assessed as new mental health surveys are undertaken. Writing in a linked Comment, Dr. Maxime Taquet and Professor Paul Harrison, from the University of Oxford, and Professor Emily Holmes, from Uppsala University and the Karolinska Institute, who were not involved in the study, said: "The first global insight into the burden of depressive and anxiety disorders during the pandemic by Santomauro and colleagues starkly highlights the impact of the pandemic on mental health globally." They echo the study authors' calls for action to strengthen mental health systems, saying: "The study should therefore urgently incentivise more research to determine the fuller geographic distribution of depression and anxiety, the prevalence of depressive and anxiety disorders, and the underpinning mechanisms to improve mental health in the context of the COVID-19 pandemic globally."

Original findings published in The Lancet (October 8, 2021):

https://doi.org/10.1016/S0140-6736(21)02143-7