COVID-19 is known to be associated with multiple changes in gene expression, but many of these are also seen in chronic brain conditions as well as in some abnormal mental conditions. A recent study published on the preprint server bioRxiv* in October 2020 uncovers the molecular basis of this association.
Though severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes predominantly respiratory symptoms, it is becoming clear that many other organ systems can also be involved. Symptoms related to the brain include anosmia, headache, memory loss, cognitive deficits including loss of concentration, and chronic tiredness, especially common in previously hospitalized COVID-19 patients.
Such symptoms could be due to direct neuronal and glial infection by the virus or indirect damage due to the infection and subsequent inflammation. The long-term persistence of such symptoms occurs in both SARS and MERS.
Some studies have detected the presence of SARS-CoV-2 RNA in the olfactory mucosa and the cerebrospinal fluid (CSF). On the other hand, experiments have failed to prove infection in neuronal organoids, and the relevance of these systems has not been established.
Thirdly, the physiological profile of many brain regions significantly affected by COVID-19 remains unclear.
Cell type-specific gene expression changes in the brain of COVID-19 patients. a, Study design. Colored triangles denote brain regions studied for each patient. b, Uniform Manifold Approximation and Projection (UMAP) of 23,626 nuclei captured from the human medial frontal cortex, colored by cell type and labeled with percent of total nuclei. Note, that as in prior reports32,34,35, the ‘Endothelial’ cluster also exhibits vascular mural cell markers. c, Differentially expressed gene (DEG) counts for each cell type (MAST with default thresholds, FDR < 0.05, Log (fold change) > 0.25 (absolute value)). The intensity of the blue color and the size of the squares are proportional to entry values. d, Example differentially expressed genes (DEGs) in COVID-19: excitatory (Ex N) and inhibitory (In N) neurons, astrocytes (Ast), oligodendrocytes (Oli), oligodendrocyte precursor cells (OPC), and microglia (Mic). e, Matrix layout for intersections of DEGs shared across and specific to each cell type. Circles in the matrix indicate sets that are part of the intersection, showing that most DEGs are cell type-specific. f, Fraction of total up- and downregulated genes (y-axis) as a function of the total number of cell types in which the differential expression occurs. Biological pathways associated with genes downregulated in COVID-19 that are common to ≥2 cell types are shown (n = 161 genes, hypergeometric test, FDR correction).
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