Serena S. Spudich is a professor of neurology and chief of the Neurological Infections and Global Neurology Division at Yale School of Medicine. David A. Hafler is a professor of neurology and immunobiology, chairman of the Department of Neurology at the Yale School of Medicine and a member of the National Academy of Medicine.

It is understandable that the world has focused so much attention on the high mortality of covid-19 in older populations. This has led to a more sanguine approach to precautions such as mask-wearing and social distancing among many who don’t consider themselves at high risk from the virus. Thankfully, most people who contract covid-19 do survive the acute illness.

But there might be consequences of infection that we did not originally predict. Many patients in our clinics complain months after recovering from the disease of difficulty with concentration, finding words and completing complicated tasks. Given that more than one hundred million people worldwide have been infected by the novel coronavirus, how the disease affects the brain might be the neurologic research question of our time.

As physicians specializing in infectious and immunologic diseases of the brain, we care for and study patients to understand the interplay of infections and the body’s immune response in altering function of the nervous system. We know from experience that viruses impact the brain in diverse ways. With some infections, there are only modest consequences with transient fatigue or headache; on the other extreme, some viruses can directly infect and destroy brain cells, causing lasting damage and resulting in permanent impairments.

In scrambling to address the many unknowns of how the virus may impact the brain, we rushed in March 2020 to create a specialty consultation service to advise on and learn from these patients. Among a panoply of different conditions, we saw patients who woke up too slowly after long stays in intensive care, who experienced new strokes and who suffered unbearable headaches. Many of these patients died from respiratory or circulatory failure. The majority survived.

The good news was that the severe confusion, headaches and other acute neurologic symptoms for most patients improved as they recovered in the hospital. But as the weeks wore on, we began to notice new syndromes, many of which seemed to persist or even emerge days or weeks after the illness. We learned of new headaches that wouldn’t go away and disturbing changes in sensation on the skin all over the body. Individuals with no prior mood problems reported severe depression or anxiety that interfered with sleep or even caused thoughts of suicide. Frustrated health-care providers and students found going back to their routines at work or school challenging due to difficulties with concentration and multitasking. Patients even presented to our emergency services with new psychoses that unexpectedly emerged, including paranoia, delusions and violent behavior.

These syndromes raise many questions: Might neurological symptoms result from a direct viral infection in the brain, or a heightened immune reaction that may in some cases lead to an unchecked, autoimmune response against cells in the brain? Our own studies and those of our colleagues around the world suggest the latter. Other symptoms might be due to an unmasking of underlying conditions triggered by exposure to the virus, such as migraine headaches or early-stage memory disorders. Finally, some symptoms might be due to or intensified by the trauma of covid-19, isolation and the stress of this tumultuous moment in history.

With all of these questions comes an imperative for research. We need large, systematic studies to characterize and determine the frequency of and risk factors for these symptoms, including in races and ethnicities that have been disproportionally affected by the pandemic. Essential to these studies will be defining the biological underpinnings of these syndromes, to help develop targeted treatments.

Cynthia Adinig has been to the hospital upwards of 20 times for debilitating symptoms related to long-haul covid-19, but has been dismissed by doctors. (Lindsey Sitz/The Washington Post)

It’s also clear that we must do everything we can — mask-wearing, physical distancing, vaccination — to prevent new infections, particularly with the expansion of more infectious variants. The demographics of patients we see in our clinic with post-covid-19 neurologic syndromes are worrisome: Many are young and otherwise healthy people. Early in the pandemic, we were concerned about long-term brain health in patients who had prolonged stays in intensive care, but in our experience, such symptoms occur even in patients who experienced mild disease and were never hospitalized. Death rates do not tell the full story; survival after covid-19 infection might not be completely straightforward.

We must harness all of the investigative tools and expertise that we have developed in infectious and autoimmune diseases of the nervous system to understand how the brain might be affected by this tiny pathogen. We call on the National Institutes of Health, research foundations and survivors of covid-19 to invest, partner and participate in solving this new biomedical mystery. And we call on the nation to halt the spread of this virus to prevent the low but real risk of lingering mental disorders.

Read more: