People who have had COVID-19 are at increased risk of developing neurological conditions within the first year after infection, according to a detailed analysis of federal data by researchers at Washington University School of Medicine in St. Louis. Movement disorders, memory problems, strokes and seizures are among the complications. Credit: Sara Moser/University of Washington School of Medicine Strokes, seizures, memory and movement disorders are among the problems that develop in the first year after infection. If you’ve had COVID-19, your brain may still be affected. Those infected with the SARS-CoV-2 virus are at increased risk of developing a range of neurological conditions in the first year after infection, according to new research. A comprehensive analysis of federal health data reveals that such complications include strokes, cognitive and memory problems, anxiety, depression and migraine headaches. “Our study provides a comprehensive assessment of the long-term neurological consequences of COVID-19.” — Ziyad Al-Aly, MD In addition, the post-COVID-19 brain is associated with movement disorders, from tremors and involuntary muscle contractions to seizures, balance and coordination difficulties, and hearing and vision abnormalities, as well as other symptoms similar to those seen with Parkinson’s disease. The findings, by researchers at Washington University School of Medicine in St. Louis and the St. Louis Veterans Affairs System, were published Sept. 22 in the journal Nature Medicine. “Our study provides a comprehensive assessment of the long-term neurological consequences of COVID-19,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at the University of Washington. “Previous studies have looked at a narrower set of neurological outcomes, mostly in hospitalized patients. We evaluated 44 cerebrovascular and other neurological disorders in both non-hospitalized and hospitalized patients, including those admitted to the intensive care unit. The results show the devastating long-term effects of COVID-19. These are part and parcel of long-term COVID. The virus is not always as benign as some people think.” Al-Aly said that overall, COVID-19 has contributed to more than 40 million new cases of neurological disorders worldwide. A comprehensive analysis of federal data by researchers at Washington University School of Medicine in St. Louis shows that people who have had COVID-19 are at increased risk of developing neurological conditions within the first year after infection. Movement disorders, memory problems, strokes and seizures are among the complications. Credit: Sara Moser/University of Washington School of Medicine Other than infection with COVID-19, specific risk factors for long-term neurological problems are lacking. “We see brain problems in previously healthy people and in people who have had mild infections,” Al-Aly said. “It doesn’t matter if you’re 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.” Very few of the study participants were vaccinated for COVID-19. This is because vaccines were not yet widely available at the time of the study, which ran from March 2020 to early January 2021. Notably, the data also predates delta, micron and other variants of COVID. “Overall, COVID-19 has contributed to more than 40 million new cases of neurological disorders worldwide.” An earlier study led by Al-Aly published in Nature Medicine found that the vaccines slightly reduced — by about 20 percent — the risk of long-term brain problems. “It’s certainly important to get vaccinated, but also important to understand that they don’t offer complete protection against these long-term neurological disorders,” Al-Aly said. The scientists analyzed about 14 million de-identified medical records in a database maintained by the US Department of Veterans Affairs. It is the nation’s largest comprehensive health care system, and patients include all ages, races, and genders. The research team then created a controlled dataset of 154,000 people who had tested positive for COVID-19 sometime between March 1, 2020, and January 15, 2021, and who had survived the first 30 days after infection. Neurological outcomes in the COVID-19 data set were compared using statistical modeling with two other groups of people who had not been infected with the virus: a control group of more than 5.6 million patients who did not have COVID-19 over the same time period; and a control group of more than 5.8 million people from March 2018 to December 31, 2019, before the pandemic left millions around the world infected and killed by the SARS-CoV-2 virus. Ziyad Al-Aly, MD, has led multiple long-term COVID studies as a clinical epidemiologist at Washington University School of Medicine in St. Louis and the St. Louis Veterans Health System. His research includes the devastating effects of the virus on the heart, kidneys and mental health. Credit: Matt Miller/University of Washington School of Medicine Brain health was analyzed by the scientists over the course of a year. Compared to those who were not infected with the virus, neurological conditions were 7% more common in people with COVID-19. Extrapolating this rate based on the number of COVID-19 cases in the U.S. translates to about 6.6 million people who have suffered brain injuries related to SARS-CoV-2. One of the most common brain-related, long-term symptoms of Covid is memory problems – colloquially called brain fog. People infected with the virus had a 77% increased risk of developing memory problems compared to those in the control groups. “These problems resolve in some people, but persist in many others,” Al-Aly said. “At this point, the proportion of people who improve versus those with long-term problems is unknown.” Interestingly, the research team noted an increased risk of Alzheimer’s disease among those infected with the virus. Compared to the control groups, there were two more Alzheimer’s cases per 1,000 people with COVID-19. “It’s unlikely that someone who had COVID-19 would escape Alzheimer’s,” Al-Aly said. “Alzheimer’s takes years to manifest itself. But what we suspect is happening is that people who are predisposed to Alzheimer’s disease may be pushed to the limit by COVID, meaning they are on a faster path to developing the disease. It’s rare but worrying.” Also, people who had the virus were 50% more likely to have a stroke compared to the control groups. This happens when a blood clot or other blockage blocks an artery’s ability to deliver blood and oxygen to the brain. Ischemic strokes account for the majority of all strokes and can lead to difficulty speaking, vision problems, cognitive confusion, loss of sensation on one side of the body, paralysis, permanent brain damage, 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 blood vessels and then cause 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, and 35% more likely to experience mild to severe headaches. They were also 42% more likely to experience movement disorders, which include 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 inflammation of the retina. They were also 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 description of the neurological consequences of COVID-19 one year after infection,” said Al-Aly. The long-term effects of COVID on the brain and other systems underscore the need for governments and health systems to develop policies, as well as public health and prevention strategies to manage the ongoing pandemic and plan for a post-COVID-19 world , Al-Aly said. “Given the colossal scale of the pandemic, addressing these challenges requires urgent and coordinated – but, so far, absent – global, national and regional response strategies,” he said. Citation: “Long-Term Neurological Effects of COVID-19” by Evan Xu, Yan Xie and Ziyad Al-Aly, 22 September 2022, Nature Medicine.DOI: 10.1038/s41591-022-02001-z This research was funded by the US Department of Veterans Affairs. the American Society of Nephrology; and KidneyCure. Data supporting the findings of this study are available from the US Department of Veterans Affairs. VA data are freely available to researchers behind the VA firewall with an approved VA study protocol.
