No Genetic Causal Relationship between COVID-19 and Herpes Zoster: A Bidirectional Mendelian Randomization Analysis.

PURPOSE

Increased incidences of herpes zoster (HZ) have been reported among COVID-19 patients, but the underlying causal mechanisms remain unclear. Inspired by an atypical case of HZ in a COVID-19 patient, we conducted a bidirectional Mendelian randomization (MR) analysis to investigate potential causal relationships.

PATIENTS AND METHODS

The genetic statistics were extracted from the COVID19-hg GWAS meta-analyses and the IEU GWAS database. MR analyses were performed using the inverse-variance weighted (IVW) method as the primary approach, with MR-Egger, weighted median, simple mode, and weighted mode methods as supplementary strategies. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept, and MR-PRESSO analysis, while outliers were evaluated with MR-radial plots.

RESULTS

The MR analysis did not support a significant causal relationship between COVID-19 and HZ. In the forward analysis, the IVW method revealed no significant associations between COVID-19 susceptibility (β = -0.053, SE = 0.182, P = 0.77), hospitalization (β = 0.060, SE = 0.069, P = 0.38), or severity (β = 0.015, SE = 0.048, P = 0.75) and HZ. Similarly, the reverse analysis showed no significant effect of HZ on COVID-19 susceptibility (β = 0.006, SE = 0.006, P = 0.33), hospitalization (β = -0.012, SE = 0.012, P = 0.32), or severity (β = -0.015, SE = 0.020, P = 0.46). Sensitivity analyses confirmed these findings, showing no substantial heterogeneity or horizontal pleiotropy.

CONCLUSION

Our findings provide no evidence of a causal relationship between genetic predisposition to COVID-19 and the risk of HZ reactivation. The observed clinical association may be attributable to non-genetic factors, such as immune suppression or stress related to COVID-19 and its treatment. Further studies are warranted to explore these alternative mechanisms and improve clinical management of HZ in the context of COVID-19.