Morphologic Findings in the Cerebral Cortex in COVID-19: Association of Microglial Changes with Clinical and Demographic Variables

Abstract

Despite the enormous interest in COVID-19, there is no clear understanding of the mechanisms underlying the neurological symptoms in COVID-19. Microglia have been hypothesized to be a potential mediator of the neurological manifestations associated with COVID-19. In most existing studies to date, morphological changes in internal organs, including the brain, are considered in isolation from clinical data and defined as a consequence of COVID-19. We performed histological immunohistochemical (IHC) studies of brain autopsy materials of 18 patients who had died from COVID-19. We evaluated the relationship of microglial changes with the clinical and demographic characteristics of the patients. The results revealed neuronal alterations and circulatory disturbances. We found an inverse correlation between the integral density Iba-1 (microglia/macrophage-specific marker) IHC staining and the duration of the disease (R = −0.81, p = 0.001), which may indicate a reduced activity of microglia and do not exclude their damage in the long-term course of COVID-19. The integral density of Iba-1 IHC staining was not associated with other clinical and demographic factors. We observed a significantly higher number of microglial cells in close contact with neurons in female patients, which confirms gender differences in the course of the disease, indicating the need to study the disease from the standpoint of personalized medicine.

Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments

“…Thus, even a mild COVID-19 in the mouse model can cause significant neuroinflammation with microglial reactivity and elevated cytokines and chemokines, akin to that observed in postmortem brain samples from COVID-19 patients [ 37 ]. A recent study employing immune-histochemical staining of autopsied brain tissues from COVID-19 patients revealed neuronal alterations and circulatory disturbances of microglia [ 40 ]. Another study demonstrated altered purinergic signaling in microglia via ADTP secretion production when exposed to SARS-CoV-2 spike protein.…”