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Three new studies on COVID-19 raise questions about the neuropsychiatric effects of mild to moderate cases that do not require hospitalization. The most alarming study reported that even in patients with mild disease who were not hospitalized, brain scans revealed post-injury contractions in global brain volume compared to controls. Two other studies have found links between higher rates of anxiety and depression.
Three new studies of COVID-19 provide new clarity and raise troubling new questions about the neuropsychiatric effects of the mild to moderate form of the disease that does not require hospitalization.
The most disturbing study used hundreds of pairs of brain MRIs from the UK Biobank taken over a few years. About half of the patients tested positive for SARS-CoV-2 between the two tests, while the other half did not. Although 96 percent of the patients who tested positive had mild disease that did not require hospital admission, examinations revealed post-injury contractures compared to controls in global brain volume, reduced gray matter thickness in the orbitofrontal cortex and parahippocampal gyrus, and changes in global brain volume. in tags. From tissue damage in areas connected to the primary olfactory cortex.
A second study, from six countries in northern Europe, prospectively followed the mental health effects of COVID-19 in 247,249 patients who did not require hospitalization. As a group, they showed a higher prevalence of depression but not anxiety. When ranked by illness severity, they found that those who had never gotten out of bed because of illness were less likely to have depression and anxiety than those who had not been diagnosed with COVID-19. However, those who had been bedridden for more than seven days were at a consistently higher risk of developing depression and anxiety than those who had never had COVID-19.
A third paper from researchers at Northwestern University examined plasma biomarkers of central nervous system injury in 64 patients treated there. Previously published results confirmed that hospitalized patients with COVID-19 encephalopathy had higher levels of plasma neurofilament light chain (pNfL) and plasma glial fibrillary acid protein (pGFAP). But among those with post-acute sequelae of SARS-CoV-2 (PASC), there was an association with blood-based evidence of neuroinflammation and increased levels of anxiety.
Barbara Hanson, Ph.D., first author of the study of plasma biomarkers, said she and her colleagues had hoped to find a plasma biomarker for PASC, or the so-called “long COVID,” but were surprised to find contact only with PASC patients with high levels. of anxiety.
“This is clearly not the direction we expected when we developed the study,” said Dr. Hanson, a postdoctoral fellow in the Kane and Ruth Dave Department of Neurology at Northwestern University. “But having this kind of evidence helps us better understand what kind of mechanisms may contribute to PASC.”
She and other neurologists said they were most impressed by the UK Biobank study that showed a reduction in brain volume after mild COVID-19.
“It was very surprising to see this kind of effect in individuals who did not need to be hospitalized,” Dr. Hanson said. It also demonstrates the usefulness of these types of long-term studies. If they did not have access to these images before patients contracted COVID-19, these comparison observations would not have been made.
However, the studies raised as many questions as they answered. Do other viral illnesses that require hospitalization lead to a slight decrease in brain volume? Do illnesses that are not severe enough to result in hospitalization but leave a person bedridden at home for a week increase the risk of depression and anxiety? And does anxiety related to illnesses other than COVID-19 raise levels of central nervous system biomarkers of infection? How long do all these effects last?
Posted in temper nature Online ahead of print on March 7, the UK Biobank study included 785 patients aged between 51 and 81 who had had their brains scanned by MRI for various reasons. Of these, 401 patients tested positive for SARS-CoV-2 after screening, while 384 did not. After an average of 141 days, a brain MRI was taken in both groups.
The previous and subsequent changes were amazing. Scans revealed significant longitudinal effects between the two groups, including greater reductions in gray matter thickness and tissue variation in the orbitofrontal cortex and parahippocampal gyrus, greater changes in tissue damage markers in regions functionally related to the primary olfactory cortex, and greater reduction in global brain volume.
In addition, tests of cognitive abilities showed a greater mean cognitive decline between the two time points in the virus-positive group.
“The findings of the limbic brain imaging may primarily be in vivo The authors conclude that hallmarks of degenerative disease spread through olfactory pathways, neuroinflammatory events, or loss of sensory input due to olfactory loss. Whether this adverse effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.”
In a statement issued with the study, the lead author noted that the amount of change associated with SARS-CoV-2 infection varies across brain regions.
“On average, affected participants showed 0.2 percent to 2 percent additional loss or tissue damage compared to uninjured participants,” said Gwenelle Dowd, assistant professor in the Nuffield Department of Clinical Neuroscience at the University of Oxford. “To understand the magnitude of these effects, large or small, it is worth placing them in the context of what happens in healthy aging. It has been previously shown that annually people lose about 0.2 percent to 0.3 percent of gray matter in areas related to memory.”
Dr speculated. David that the abnormalities are linked to the loss of the sense of smell. “Repeated olfactory loss has been shown in previous studies to lead to a loss of gray matter in areas of the brain related to smell. Unfortunately, we do not have information on the symptoms of affected participants, such as olfactory loss.”
Regarding whether changes in brain volume are temporary or permanent, she noted that a research paper from Germany published in 2021 showed slow but significant recovery from new cortical dysfunction and cognitive impairment in a series of chronic COVID-19 patients.
Jennifer Frontera, MD, professor of neurology in the department of neurological care and stroke at New York University’s Grossman School of Medicine, said she found the paper “very compelling.”
“The strength of this study is that they underwent MRI before and after COVID-19,” said Dr. Frontera.
However, she expressed caution in interpreting the clinical significance of the findings. “I would hesitate to draw a direct line between the volumetric changes and the cognitive capabilities of the population that has been infected with the mild COVID-19 virus,” said Dr. Frontera. “The vast majority are unlikely to have cognitive problems.”
mental health effects
Dr. Hanson’s study was published online in preprint on March 7 in Neuroscience: Neuroimmunology and Neuroinflammation, included nine patients hospitalized with COVID-19 encephalopathy on blood draw; Nine were previously hospitalized with COVID-19 but diagnosed with severe SARS-CoV2 (PASC) sequelae, 38 were never hospitalized but had PASC, and eight were healthy controls.
Whether or not they were hospitalized with acute SARS-CoV-2 infection or not, patients subsequently diagnosed with PASC showed “similar PASC symptoms, lower quality-of-life standards, and cognitive impairment,” the paper noted. However, in plasma biochemical tests, only those with anxiety had significantly increased neuronal scores, as measured by serum GFAP/NfL.
The research paper stated that “Quantitative measurements of anxiety and depression revealed a linear relationship between increased neuronal scores and anxiety, but not depression, in patients with PASC neuroblastoma.” “These data shed new light on the SARS-Cov-2 neurodegenerative disease and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.”
A neurologist who recently published results from the International Registry of Hospitalized Patients with COVID-19 noted that the study of central nervous system biomarkers was relatively small.
said Anna Marisa Cervantes-Arslanian, MD, chief of neurological care and neuroinfection disease at Boston Medical Center and assistant professor of neurology, neurosurgery and medicine at Boston University School of Medicine.
The third new study was published online in preprint on March 14 in The Lancet Public Health, also sheds light on COVID-19’s mild impact on mental health. The observational study included 247,249 patients from Denmark, Estonia, Iceland, Norway, Sweden and the United Kingdom, 4 percent (9979) of whom were diagnosed with COVID-19 but never hospitalized.
As a group, participants diagnosed with COVID-19 had a slightly higher prevalence of mental health effects than participants without COVID-19, with an 18 percent higher prevalence of depressive symptoms and a 13 percent higher prevalence of poor sleep quality. However, they did not have a higher prevalence of anxiety.
The most interesting results emerged when researchers compared COVID-19 participants who were bedridden at home versus those who had never been bedridden. Those who never got to bed had a 17% lower risk of depression and a 23% lower risk of developing anxiety than those who had never been diagnosed with COVID-19. However, individuals who remained bedridden for more than seven days were 61 percent more likely to develop depressive symptoms and 43 percent more likely to develop anxiety than those who were never diagnosed with COVID-19.
The researchers concluded that the findings, “call for increased vigilance about the development of negative mental health among patients with the severe acute illness phase of COVID-19.”