Pathology of COVID-19 affects CNS with longer symptom course

CHICAGO — The neurological pathology of COVID-19 becomes more complex as symptoms persist and tends to affect the central nervous system more prominently, according to an expert at the American Neurological Association annual meeting.

“It hasn’t gone away — there are 400 people still dying every day from COVID in the United States,” Avindra Nath, MD, clinical director of intramural research at the National Institute of Neurological Disorders and Stroke at NIH, said during the presentation. “It’s still 10-times more [than the amount of] people [who] die of influenza.”

All coronaviruses cause neurological complications, Nath explained, each of which possesses different receptors that result in different pathologies. And while clinicians and researchers have become focused on the respiratory effects of COVID-19, the virus affects the CNS and produces longer-lasting health issues.

The long-term devastation of COVID and complications from infection, Nath said, all affect brain function. Although there are many variants to COVID-19, the differences between them are not clear with respect to how each one affects the CNS.

However, Nath noted, it appears that effects of newer strains of the virus tend to linger longer than earlier variants. “The virus may be getting persistent,” he said.

Neurological impacts, according to Nath, can be divided into three categories: acute, subacute and chronic. Acute impacts include loss of smell, stroke, difficulty with respiration and recovery, or sudden death during sleep. Subacute affects include inflammatory syndromes such as encephalomyelitis, hemorrhagic encephalopathy and multisystem inflammatory syndrome, while chronic affects are defined by what is known as long COVID.

With respect to long COVID, Nath said there is no consensus on a definition — the diagnosis was coined by patients themselves. However, he offered two broad categories based on symptom course: one in which the severity of symptoms increases and does not resolve as time goes on, and another in which symptoms are initially mild, then decrease sharply or disappear over days or weeks, with new symptoms suddenly appearing and increasing. The latter, he added, is challenging to address due to the intermittent healthy middle gap, in which patient and doctor are left to determine whether the two episodes are related.

Patients dealing with long COVID can be easily divided into four subcategories between those who suffer from respiratory, cognition, autonomic or neuralgic pain issues.

The main pathogenetic factor at issue, Nath said, is whether COVID can enter the brain through nasal mucosa. While studies have shown that a small amount of the virus was found in very few individuals at autopsy, the fact that it is rarely detected may demonstrate that direct invasion of the virus likely does not explain neurological pathology.

“I think we need to look at all neuronal injury, vascular injury, biomarkers. We need to start immunotherapies,” Nath said to conclude his presentation. “And at the same time, study disease pathophysiology together.”