In this study we conducted
RNA sequencing on two brain regions (olfactory bulb and amygdala) from subjects who died from
COVID-19 or who died of other causes. We found several-fold more transcriptional changes in the olfactory bulb than in the amygdala, consistent with our own work and that of others indicating that the olfactory bulb may be the initial and most common brain region infected. To some extent our results converge with pseudotime analysis towards common processes shared between the brain regions, possibly induced by the systemic immune reaction following
SARS-CoV-2 infection. Changes in amygdala emphasized upregulation of
interferon-related
neuroinflammation genes, as well as downregulation of synaptic and other neuronal genes, and may represent the substrate of reported acute and subacute
COVID-19 neurological effects. Additionally, and only in olfactory bulb, we observed an increase in angiogenesis and platelet activation genes, possibly associated with microvascular damages induced by
neuroinflammation. Through coexpression analysis we identified two key genes (CAMK2B for the synaptic neuronal network and
COL1A2 for the angiogenesis/platelet network) that might be interesting potential targets to reverse the effects induced by
SARS-CoV-2 infection. Finally, in olfactory bulb we detected an upregulation of olfactory and taste genes, possibly as a compensatory response to functional deafferentation caused by viral entry into primary olfactory sensory neurons. In conclusion, we were able to identify transcriptional profiles and key genes involved in
neuroinflammation, neuronal reaction and olfaction induced by direct
CNS infection and/or the systemic immune response to
SARS-CoV-2 infection.