The Neurologic Consequences of COVID-19
There have been many anecdotal reports and small studies regarding neurologic symptoms during the acute phase of COVID-19 as well as after the acute phase. Now, at the American Academy of Neurology Virtual Annual Meeting, May 17-22, 2021, both retrospective and prospective observational studies are beginning to quantify these neurologic effects.
Neurologic Symptoms in Acute COVID-19
Some of the earliest reports from Wuhan China showed neurologic symptoms in approximately one-third of people with COVID-19. A report from the UK of 153 patients hospitalized with COVID-19 who had neurologic symptoms showed cerebrovascular (more common in people over age 60) and neuropsychiatric symptoms (more common in those under age 60) to be most prevalent. Multiple reports from have documented a higher risk of stroke in people with COVID-19 without other risk factors for stroke. A cohort report from the US showed that across 10 hospitals, 82% of 509 people admitted to ICU with COVID-19 had neurologic symptoms, with 68% having encephalitis.
Data were presented from the European ENERGY registry of 214 people with COVID and the GCSNeuroCOVID cohort of 3,055 people with COVID-19. Of these individuals, approximately 80% had neurologic symptoms. The most common clinically verified symptoms were encephalopathy (~50%), which was associated with a 5.5 times higher risk of in-hospital mortality, followed by coma (17%), stroke (~3%), sensory symptoms, and seizures. Other neurologic symptoms included abnormal brainstem reflexes, aphasia, abnormal tone, movement abnormalities, and dysautonomia. Meningitis and myelopathy were seen in fewer than 0.2% of individuals. The presence of neurologic symptoms correlated with age, severity of COVID-19, and the presence of an underlying neurologic condition. The risk of in-hospital mortality was over twofold higher in people with underlying neurologic conditions, and the presence of any neurologic symptom during acute COVID-19 increased the risk of mortality sixfold.
Long-COVID or Post-acute COVID-19 Neurologic Issues
It has also become clear that a subset of people have persistent or develop newly emergent neurologic symptoms after recovery from acute COVID-19—termed long-COVID, long-hauler COVID, or postacute sequelae of SARS-CoV-2 infection (PASC). As suggested by the last of these terms, PASC can occur even when the illness caused by SARS-CoV-2, COVID-19, did not. No prevalence data are yet available. Considering the high rate of infection and illness from SARS-CoV, if only 1% of people with documented infections develop PASC, that would be 1.4 million cases. A preliminary study from a postCOVID neurology clinic at Yale showed that 67% of people with PASC had not been hospitalized for COVID-19, and some did not ever have a positive test for SARS-CoV-2 because of limited availability of testing and possibly poor test sensitivity when they were tested.
Reported symptoms include fatigue, memory dysfunction, attention difficulties, brain fog, sensory disturbances, pain or headache, and motor and autonomic dysfunctions. In an international survey answered by 3,762 people, the most common neurologic symptoms were cognitive (eg, brain fog, memory issues, slurring words, and speech/language issues) and sensorimotor (eg, sensory changes, dizziness/balance, neuralgia, tremors, vibrating sensations, headache, insomnia, and sleep difficulties). Some cases of psychosis have been reported, and in 1 such case, a novel autoantibody was found. Another study found that people with PASC had higher levels of inflammatory markers in their cerebrospinal fluid.
National Institutes of Health Response
Prior to presentation of these data, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease and chief medical advisor to President Biden, and Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke were on hand to answer questions from the Academy regarding COVID-19 and neurologic consequences of the pandemic.
Dr. Fauci noted, "We've been chasing myalgic enchephalitis and chronic fatigue syndrome without ever knowing what the etiologic agent was. Now we have an absolutely well-identified etiologic agent causing a highly parallel condition that should be very helpful to understand these postviral syndromes that have been mysterious to us for years. Maybe this will give us a chance for that breakthrough."
Dr. Koroshetz said "the virus affects systems in the body that we know are essential to the brain, particularly the vascular system. . . and clearly the nervous system takes a hit with encephalopathies seen clinically and breakdown of the blood-brain-barrier seen on autopsied tissue. The big question is, what are the long-term consequences on the nervous system? There is now funding available for people to study PASC and try to understand the condition."
Both Dr. Koroshetz and Dr. Fauci expressed optimism that having 4 highly effective vaccines would result in lower rates of infection and illness from SARS-CoV-2. They emphasized that there is still much to learn and develop from understanding why SARs-CoV-2 has such a broad range of effects in different age groups, whether retransmission is possible after vaccination, how to more quickly detect and treat the virus so that fewer severe cases of COVID occur, and how to detect, treat, and eventually prevent PASC.