Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation

Neuroinflammation and COVID-19

“…In addition to effects on the BBB, serum cytokines may directly impact neuronal functions. Recent work found serum CCL11 levels were positively correlated with post-acute cognitive deficits in COVID-19 patients and that in a mouse model, injection of CCL11 was sufficient to impair the generation of new neurons in the hippocampus [ 22 ]. Understanding the serum cytokines associated with cognitive impairment will be an important step in identifying biomarkers for patients at risk of PASC.…”

“…Current evidence suggests that SARS-CoV-2 infection may promote pro-inflammatory cytokine release in the CNS, as analysis of cerebrospinal fluid (CSF) from COVID-19 patients with neurological symptoms found elevated levels of IL-1β, TNF-α, IL-8, IL-6, IL-15, MCP-1, and MIP-1β [ 23 , 24 ]. Even during mild SARS-CoV-2 infection in a mouse model, inflammatory cytokines (IL-6, CXCL5, CCL11) were elevated at acute and post-acute timepoints in the CSF [ 22 ]. This could directly impact CNS function as many of these cytokines are known to target various neural cell types.…”

“…Microglial activation induced by injection of S1 into the meninges of rats correlated with sickness behavior, anxiety, and cognitive deficits [ 59 , 65 ]. A mouse model of mild COVID-19 found that activated microglia persisted for up to 7 weeks post infection, suggesting that microglia could be partly responsible for neurological PASC [ 22 ]. However, detailed, mechanistic studies are needed to define how SARS-CoV-2 induced microglial activation impacts patient outcomes.…”

“…Histopathological analyses of SARS-CoV-2 infected primates identified evidence of neuronal death [ 67 ]. Two publications demonstrated that rodent models of acute COVID-19 exhibit decreased neurogenesis in the dentate gyrus region of the hippocampus and a loss of myelination in subcortical white matter tracts, with the former study confirming loss of neurogenesis in humans [ 22 , 68 ]. Multiple post-mortem studies of human and primate tissue noted increased GFAP staining, but more data is needed to understand alterations in astrocyte function and the sources of astrocyte activation [ 41 , 42 ].…”

COVID fog demystified

“…Given the sheer scale of infections, there is a pressing need to understand how cognitive dysfunction emerges in long COVID. In this issue of Cell, a new paper by Ferna ´ndez-Castan ˜eda and colleagues (Ferna ´ndez-Castan ˜eda et al, 2022) begins to address this need. Using mice as a model, they expressed human ACE2, the viral entry receptor required for successful COVID infection.…”