Causal affects of Nasal microbiota on COVID-19 phenotypes: A two-sample bidirectional Mendelian randomization study

<bold>Background:</bold> The nasal microbiome modulates the host immune response and influencing the susceptibility and severity of respiratory infections. However, the causal effects of nasal microbiota on COVID-19 phenotypes are unclear. <bold>Methods:</bold> We performed bidirectional Mendelian randomization using summary statistics from the 4D-SZ cohort’s nasal microbiome data and the latest COVID-19 host genetics initiative. We used the inverse-variance weighted as the primary method to estimate the causal effects and performed sensitivity analyses to assess the robustness of the results. <bold>Results:</bold> We found evidence of a causal effect of family Lactobacillaceae (odds ratio (OR), 1.028; 95% confidence interval (CI), 1.002–1.054; P = 0.035) and species Anaerococcus nagyae (OR, 1.046; 95% CI, 1.000–1.093; P = 0.048) on increasing the risk of COVID-19 susceptibility. Moreover, family Lactobacillaceae (OR, 1.044; 95% CI, 1.016–1.074; P = 0.002) also increased the risk of COVID-19 hospitalization. On the other hand, order Micrococcales (OR, 0.902; 95% CI, 0.825–0.986; P = 0.024) and genus Corynebacterium (OR, 0.691; 95% CI, 0.491–0.973; P = 0.034) decreased the risk of COVID-19 severity. We also detected reverse causation from several taxa to COVID-19 phenotypes, suggesting that COVID-19 infection may alter the nasal microbiota composition. <bold>Conclusions:</bold> This study provides novel insights into the potential causal relationship of nasal microbiome with COVID-19 phenotypes. Our findings may have implications for the prevention, diagnosis, and treatment of COVID-19. Further studies are needed to validate the causal effects and elucidate the underlying mechanisms.