The Upper Respiratory Tract (URT) is an important site for the predisposition and multiplication of the SARS-CoV-2 virus. Therefore, URT is a critical site to investigate the changes in the microbiome caused by the SARS-CoV-2 infection. In this study, we have used the whole genome shotgun metagenomic approach to investigate URT swab samples (n=96) collected from SARS-CoV-2-positive individuals (n=48) (non-hospitalised but symptomatic) and healthy controls (n=48) belonging to five districts of central India. This study aims to compare the phageome diversity and investigate the correlation of the phageome profiles with the sample type (SARS-CoV-2 or Control) to determine the nature of phage-host interactions and to assess the effect of SARS-CoV-2 viral load over host and phage abundance. The results showed that Detrevirus was a prominent bacteriophage in controls and Maxrubnervirus in SARS-CoV-2 samples. Higher Chao1 indices were observed in the SARS-CoV-2 group for bacteria (886.00 vs. 351.00, p < 0.0001) and phages (39.00 vs. 16.00, p = 0.0002). The Simpson index was lower for bacteria (0.88 vs. 0.93, p = 0.0024) and higher for phages (0.86 vs. 0.79, p = 0.0384). Ct-dependent variations in bacterial (H = 6.69, p = 0.035) and phage (H = 8.97, p = 0.011) abundances were also observed. Disrupted host-phage interactions were observed in SARS-CoV-2 samples, with a weaker model fit (logistic R2 = 0.7425) than controls (logistic R2 = 0.9265). These findings highlight the need to integrate virome and bacteriome analyses with potential diagnostic, prognostic, and therapeutic applications for infectious disease research.

The authors have declared no competing interest.

The authors are thankful to CSIR-NEERI for providing funds under project OLP-57 (March 2023 -April 2024) for conducting this study

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