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NEUROIMMUNOLOGY

Shared COVID- and chemo-fog

Cell https://doi.org/10.1016/j.cell.2022.06.008 (2022)

Even after seemingly mild infection with SARS-CoV-2, many suffer from persistent cognitive impairment, or ‘COVID brain fog’, that resembles the ‘chemo-fog’ associated with cancer therapy. Chemo-fog is known to be mediated by microglial reactivity and subsequent neural dysregulation, and a study published in Cell investigated whether COVID recruits similar pathophysiological processes. In a mouse model of mild respiratory SARS-CoV-2 infection, the authors observed elevated cytokines and chemokines in serum and cerebrospinal fluid, increased microglial reactivity specifically in white matter, a loss of oligodendrocytes and myelin, and decreased hippocampal neurogenesis. These changes persisted for many weeks after the respiratory infection had cleared, and had human counterparts: brain tissue from patients with COVID-19 also showed white-matter-specific microglial reactivity and, intriguingly, cytokine CCL11 levels were higher in the plasma of patients with long-COVID who had ‘brain-fog’ than in plasma from patients without cognitive symptoms. Systemic CCL11 injection in mice induced white-matter microglial reactivity in hippocampus, along with impaired neurogenesis. Mild respiratory influenza in mice caused similar neuroinflammation and hippocampal pathology, but only transient subcortical white-matter changes. This work starts to unravel the mechanisms that underlie persistent COVID-related cognitive impairments, opening the door for future studies on how these mechanisms may depend on COVID-19 variant, vaccination status and age.

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Correspondence to Charlotte Arlt.

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Arlt, C. Shared COVID- and chemo-fog. Nat Neurosci 25, 838 (2022). https://doi.org/10.1038/s41593-022-01120-7

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