'Long COVID' neurological symptoms traced to infected immune cells: Japan researchers

TOKYO -- Nerve disorder symptoms experienced by some COVID-19 patients may be caused by the infection of immune system cells that clean up the brain, a research team at Tokyo's Keio University has found.

People battling long-term effects of a coronavirus infection or so-called "long COVID" sometimes exhibit symptoms associated with central nervous system damage, such as convulsions, cognitive impairment, and "brain fog," a catchall term that includes low concentration, forgetfulness, confusion, and slowed thinking.

The coronavirus can enter the brain, but it is difficult for it to invade nerve cells themselves, and the mechanism for how the brain was infected had remained a mystery. What was known was that COVID-19 patients experienced a buildup of inflammatory substances in their brains.

Seeking to unravel what was happening, a Keio University research team led by neurology professor Hideyuki Okano used induced pluripotent stem (iPS) cells to produce cells including neurons and "microglia," a type of immune cell that cleans unwanted substances out of the brain. They infected these cells with imitation "pseudoviruses" resembling the original coronavirus and subsequent strains, including the omicron variant.

Of all the cell types in the experiment, the team found that only the microglia were infected by all the pseudovirus strains at a high rate. The researchers believe that infected microglia begin behaving abnormally or dying, resulting in the boost in inflammatory substances found in the brains of COVID-19 patients and, subsequently, neural tissue damage.

The study results raise the possibility that in some patients, the coronavirus is not entirely eliminated from the brain due to a decline in microglia and other immune functions, resulting in continued microglia infection and prolonged aftereffects.

"Anti-inflammatory drugs and drugs that suppress the function of substances released by microglia could be a treatment for (COVID-19's) aftereffects," commented research team member Yoshitaka Kase, a specially appointed lecturer in neuroscience at Keio University.

The results of the study were published in the journal Experimental Neurology.

(Japanese original by Ryo Watanabe, Science & Environment News Department)