Hydrogen Sulfide (H₂S)-Producing Oral Bacteria May Protect Against COVID-19

COVID-19 mortality rates have varied dramatically across the globe. Yet the reasons behind these disparities remain poorly understood. While recent research has linked gut microbes to these variations, the role of oral bacteria, a main port of entry for the coronavirus, remains unexplored. We investigated the relationship between oral microbiota and COVID-19 mortality rates across eight countries. Raw sequencing data of 16S rRNA regions from oral microbiota in 244 healthy subjects from eight countries were obtained from public databases. We employed a generalized linear model (GLM) to predict COVID-19 mortality rates using oral microbiota composition. GLM revealed that high abundances of hydrogen sulfide (H₂S)-producing bacteria, particularly Treponema, predicted low COVID-19 mortality rates with a markedly low p-value. Unsupervised clustering using a combination of LIGER and t-SNE yielded four oral microbiome "orotypes." Orotypes enriched in H₂S-producing bacteria coincided with lower mortality rates, while orotypes harboring Haemophilus or Rothia were associated with increased vulnerability. To validate our findings, we analyzed influenza mortality data from the same countries, observing similar protective trends. Our findings suggest that oral bacteria-produced H₂S may serve as a critical initial defense against SARS-CoV-2 infection. H₂S from oral bacteria may prevent infection through antiviral activity, blocking ACE2 receptors, suppressing cytokines, and boosting antioxidants. This highlights the oral microbiome's role in COVID-19 outcomes and suggests new preventive and therapeutic strategies.