Cognitive Impairment in Long COVID Mirrors Post-Chemotherapy Effects

Stanford University neuro-oncologist Michelle Monje, MD, PhD, along with Akiko Iwasaki, PhD, of Yale University, and David Putrino, PhD, of Mount Sinai Health System, has discovered that chemotherapy and COVID-19 infection cause neuro-inflammation in similar ways.

“I worried back in the spring of 2020 that we would perhaps see a syndrome very similar to what we see after cancer therapy, that we might start to see a cognitive syndrome characterized by things like impairment in memory, executive function, attention, speed of information processing, multitasking,” Dr. Monje told STAT. “And then, you know, within months, reports of exactly that sort of complaint started to emerge.”

Dr. Monje and colleagues set out to investigate whether the physiologic process causing long COVID-related cognitive impairment mirrored the way that methotrexate directly stimulates certain microglia in the brain’s white matter to turn astrocytes neurotoxic and damage the formation of myelin. The researchers infected mice with a mild form of COVID-19. In addition, they studied brain samples from 9 patients who died from COVID-19 infection and serum samples from patients with long COVID with or without cognitive impairment.

In patients with long COVID, the scientists found high levels of cytokines and chemokines and signs of microglial activity similar to that observed in the brains of patients who have undergone chemotherapy. In particular, one chemokine linked to cognitive impairment was higher in patients with long COVID “brain fog” than in those who did not report cognitive symptoms.

Further studies are required to build on the basic science and determine whether treatments for “chemo brain” could help with COVID-related cognitive impairment.

Sources: STAT, Jan. 28, 2022; Fernández-Castañeda A, Lu P, Geraghty AC, et al. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. bioRxiv. 2022 Jan 10;2022.01.07.475453.