Bioinformatic analyses suggest augmented interleukin-17 signaling as the mechanism of COVID-19-associated herpes zoster.

Herpes zoster results from latent varicella zoster virus reactivation in the dorsal root ganglia, causing blistering rash along the dermatomal distribution and post-herpetic neuralgia. Increasing studies indicated that there may be a correlation between herpes zoster and COVID-19. Nevertheless, the detailed pathophysiological mechanism is still unclear. We used bioinformatic analyses to study the potential genetic crosstalk between herpes zoster and COVID-19. COVID-19 and herpes zoster were associated with a similar subset of genes involved in "cytokine-cytokine receptor interaction," "Jak-STAT signaling pathway," and "IL-17 signaling pathway," including TNF, IL10, ESR1, INFG, HLA-A, CRP, STAT3, IL6, IL7, and IL17A. Protein-protein interaction network assay showed that the combined gene set indicated a raised connectivity as compared to herpes zoster or COVID-19 alone, particularly the potentiated interactions with APOE, ARSA, CCR2, CCR5, CXCL13, EGFR, GAL, GP2, HLA-B, HLA-DRB1, IL5, TECTA, and THBS1, and these genes are related to "cytokine-cytokine receptor interaction". Augmented Th17 cell differentiation and the resulting enhanced IL-17 signaling were identified in both COVID-19 and herpes zoster. Our data suggested aberrant interleukin-17 signaling as one possible mechanism through which COVID-19 could raise the risk of herpes zoster.