Anosmia is common in
COVID-19 patients, lasting for weeks or months following recovery. The
biological mechanism underlying olfactory deficiency in
COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the
proteins required for
SARS-CoV-2 infection. A recent study suggested that
anosmia results from downregulation of
olfactory receptors. We hypothesized that
anosmia in
COVID-19 may also reflect
SARS-CoV-2 infection-driven elevated expression of regulator of
G protein signaling 2 (RGS2), a key regulator of
odorant receptors, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published
RNA-sequencing datasets, 580 individuals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC = 14.5, Padj = 1.69 × 10-5 and FC = 2.4; Padj = 0.001, per dataset). Additionally, RGS2 expression was strongly correlated with
PTGS2, IL1B, CXCL8, NAMPT and other
inflammation markers with substantial upregulation in early
infection. These observations suggest that upregulated expression of RGS2 may underlie
anosmia in
COVID-19 patients. As a regulator of numerous
G-protein coupled receptors, RGS2 may drive further neurological symptoms of
COVID-19. Studies are required for clarifying the cellular mechanisms by which
SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in
inflammation. Insights on these pathway(s) may assist in understanding
anosmia and additional neurological symptoms reported in
COVID-19 patients.