Cerebrum Spring 2021

the study . “Some had horrible fever and were very sick for two or three weeks, but others had felt they just had a cold for a few days. There was no association between initial severity and later symptoms.” “Brain fog”—the kind of memory, thinking, and focusing problems that Ehekircher describes —was the most common neurological symptom, affecting 81 percent of patients. [Such phenomena might arguably reflect, at least in part, anxiety or depression surrounding the illness, or the stress of living in a world in turmoil. A study now in progress might help illuminate this question.] In addition to cognitive dysfunction, two-thirds had persistent headache, and more than 50 percent had numbness and tingling, muscle pain, and/or disorders of taste and smell. Nearly one-third had tinnitus or blurred vision. The patients in the study were predominantly female (70 percent) and young (average age, 43), mirroring sex and age demographics for Long Covid generally. Whether strictly biological or partly psychological, the mental effects of Long Covid are apparently substantial. A self- administered cognitive assessment of 84,000 people in the UK found those who had had confirmed or suspected Covid-19 one to three months earlier performed more poorly than others in many ways. “There were particular deficits in executive function— decision-making and concentration—and higher language functions,” says Adam Hampshire , of the Computational, Cognitive, and Clinical Neuroimaging Laboratory at Imperial College London, first author of the paper, which has yet to be peer reviewed. His preliminary findings accord with subjective reports, he says. Deficits were most marked in the patients who had been sickest: the equivalent of an 8.5-point drop in IQ for those who had needed ventilators. Declines were more modest but still significant in individuals who had remained at home. “A lot of these people say they have sleep disturbances,” Hampshire says. “And if you look at the cognitive pattern, it’s similar to what you’d expect after several days without sleep: brain fog, trouble finding words, forgetting what you’re doing. What we don’t know is: what’s cause, what’s effect?” Depression and anxiety “had little association with cognitive performance,” Hampshire observes. But such mental maladies are a significant problem in their own right. One study examined records of 62,354 patients, both hospitalized and non-hospitalized, weeks to months after their bouts with Covid-19, and found the incidence of psychiatric symptoms pronounced enough for clinical diagnosis (most frequently, anxiety and mood disorders) to be 18 percent. This was significantly more than the rate in comparison groups of individuals who had had other illnesses. Among Covid survivors with no prior psychiatric history, the

The “music” involves a good deal more than fatigue. Sufferers frequently find it hard to think, focus, or remember. Some become clinically depressed or anxious. A galaxy of physical problems, most prominently shortness of breath, but including diverse aches, pains, and troubling symptoms fill out the picture of what has come to be called “Long Covid” or “Long- haul Covid.” “I suspect that much of this broad effect is related to some kind of neurological injury, whether to the brain, muscles, or immune system, and needs to be really studied,” says Nath. Such common problems as racing pulse, constipation, dizziness due to low blood pressure, or even shortness of breath, may reflect dysfunction in the autonomic nervous system. In recent months in particular, research and clinical efforts have increasingly focused on Long Covid. Dozens of online support groups for sufferers have appeared, along with an expanding universe of clinics, nationwide and abroad, dedicated to their care. complications. This included more cytokines and activated B cells than in the bloodstream, and antibodies that target both the viral spike protein and brain tissue. “This not only suggests viral invasion, but that neurological symptoms might be driven by autoantibodies—think of an autoimmune condition like multiple sclerosis,” he says. “That one of the antibodies specific to spike protein is also binding to human tissue suggests that molecular mimicry seen in other viral diseases could also be here.” Such a process, Song says, might explain the tenacity of Long Covid. “In a lot of these kinds of diseases, the autoimmune response persists for a decade. It’s like a floodgate: Once it’s open, you can’t close it back up.” While estimates vary widely, from ten percent upward, chronic problems clearly bedevil an enormous number of Covid-19 survivors. One study of 143 patients who had been hospitalized for Covid found that 87.5 percent had at least one persistent Covid-19-related symptom, chiefly fatigue and shortness of breath. Two months after their disease began; 55 percent had three symptoms or more. Neurological symptoms in Long Covid can be diverse, persistent, and by no means limited to those who had been ill enough to require hospitalization. In a series of 100 patients at a Northwestern Covid-19 clinic who had neurological problems six weeks after initial Covid diagnosis, 85 percent still had four or more symptoms an average of three months later. “These patients had had mild Covid, in that they had never needed oxygen,” says Edith Graham, a clinical neuroimmunology fellow at Northwestern and lead author of In a study (which has not undergone peer review), Eric Song , a researcher at Yale University, and his colleagues found evidence of immune activity in the cerebrospinal fluid (CSF) of Covid patients who had neurological



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