The public often thinks of COVID-19 as a respiratory illness that can cause breathing difficulties.
However, an article published in the journal Science on January 20 indicates that in some circumstances, it can also have devastating consequences on the central nervous system.
Citing 15 scientific papers, the authors noted that "myriad neurological complications—including confusion, stroke, and neuromuscular disorders—manifest during acute COVID-19".
"Furthermore, maladies such as impaired concentration, headache, sensory disturbances, depression, and even psychosis may persist for months after infection, as part of a constellation of symptoms now called Long Covid," wrote Yale University professor of neurology Dr. Serena Spudich and Dr. Avindra Nath, clinical director the National Institute of Neurological Diseases and Stroke at the U.S. National Institutes of Health.
Moreover, the two authors stated in their article that these neuropsychiatric symptoms can strike younger people.
"Many people who experience neurologic symptoms that linger after acute COVID-19 are less than 50 years old and were healthy and active prior to infection," they wrote.
Spudich and Nath stated that the majority of these younger people "were never hospitalized during their acute COVID-19 illness, reflecting mild initial disease".
"The pathophysiological mechanisms are not well understood, although evidence primarily implicates immune dysfunction, including nonspecific neuroinflammation and antineural autoimmune dysregulation," they wrote.
"It is uncertain whether unforeseen neurological consequences may develop years after initial infection," they added. "With millions of individuals affected, nervous system complications pose public health challenges for rehabilitation and recovery and for disruptions in the workforce due to loss of functional capacity. There is an urgent need to understand the pathophysiology of these disorders and develop disease-modifying therapies."
One of the studies cited was a U.K.-wide examination of hospitalized patients, published in the Lancet in 2020.
Spudich and Nath pointed out that this study "identified the most common neurologic conditions as anosmia (loss of smell), stroke, delirium, brain inflammation, encephalopathy, primary psychiatric syndromes, and peripheral nerve syndromes".
Spudich and Nath also stated that "the preponderance of evidence from CSF [cerebrospinal fluid] and brain tissue suggests that immune activation and inflammation within the CNS [central nervous system] is the primary driver of neurologic disease in acute COVID-19".
They cited another paper, published in the Lancet Neurology in 2020, focusing on autopsy studies of patients with acute COVID-19. It showed "infiltration of macrophages, CD8+ T lymphocytes in perivascular regions, and widespread microglial activation throughout the brain".
A third study cited, which was published in Genome Medicine in 2021, examined single-cell analysis of brain tissue. Spudich and Nath wrote that it "also confirmed CD8+ lymphocyte infiltration and microglial activation" even without evidence of the SARS-CoV-2 RNA being detected in the brain parenchyma (functional tissue, such as neurons and glial cells, as well as collagen proteins).
"The robust, generalized, and SARS-CoV-2–specific immune responses observed in the CNS [central nervous system] are puzzling in the absence of readily detectable virus and may suggest transient infection of the brain very early in infection or low concentrations of viral antigen in the CNS," Spudich and Nath wrote.
Citing a 2020 study in the Journal of the American Medical Association Neurology, they pointed out that acute COVID-19 "is associated with heightened risk of stroke compared with influenza illness of similar severity, even after correcting for stroke risk factors".
"Overt cerebrovascular events during acute COVID-19 often occur in those with vulnerabilities to vascular disease (such as advanced age and cardiac disease)," Spudich and Nath stated.
The authors acknowledged that it's difficult to consider approaches to treating Long Covid, given the diversity and breadth of symptoms and the challenges of determining which ones might be due to the SARS-CoV-2 virus versus pre-existing or coincidental conditions.
"The problem is not the sniffles," Furness told the moderator, Dr. Brenda Hardie, at the time. "The problem is what the virus is doing elsewhere in the body from the toes to the testes to the brain. It is causing autoimmune disease. It is causing loss of brain tissue.
"We haven’t seen that in children because we haven’t looked," Furness emphasized. "But we have seen it in adults, literally—brain tissue disappearing."