Upper Respiratory Tract Microbiome Profiles in SARS-CoV-2 Delta and Omicron Infected Patients Exhibit Variant Specific Patterns and Robust Prediction of Disease Groups

The pandemic caused by SARS-CoV-2 virus is the reason for many deaths globally. It is hypothesized that the upper respiratory tract (URT) microbiome shares similarity with lung microbiota and can modulate host immune responses to the virus. During the pandemic, several SARS-CoV-2 variants have emerged with different clinical outcomes and immune dysfunction, yet their association with changes in the URT microbiome has not been identified which may provide an assessment of lung health in presence of those variants with differential disease outcomes. In this study, we sequenced V3-V4 region of 16S rRNA gene from URT microbiome of healthy controls, Delta and Omicron infected patients from Eastern India that showed higher inter-individual diversity (ß) and lower intra-individual diversity (a) in COVID-19 patients compared to healthy controls. Healthy control microbiome showed enrichment of commensals like Streptococcus symci, Prevotella melaninogenica, Neisseria perflava, Veillonella tobetsuensis, Veillonella nakazawae, Haemophilus parainfluenzae, Fusobacterium pesudoperidonticum and Bifidobacterium longum compared to COVID-19 samples. Ct value of patients significantly positively correlated with Streptococcus symci and Streptococcus toyakuensis indicating a possible inverse relation with viral load. We also observed few bacterial taxa like Staphylococcus caprae, Pseudomonas aeruginosa, Vibrio tritonious, and Rothia mucilaginosa are discriminating Omicron from Delta which is, in turn, enriched mostly with Enterobacter mori, Acinetobacter baumannii, and Klebsiella pneumoniae. Further investigation showed nine control associated bacteria had higher to lower trend among three groups viz., Control>Omicron>Delta. These bacteria also contributed to successful prediction of disease groups with high accuracy (90%±0.5) by random forest analysis.