Disruption in the Host-Phage Dynamics and Altered Microbial Diversity in the Upper Respiratory Tract of SARS-CoV-2 Infected Individuals

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 R ² = 0.7425) than controls (logistic R ² = 0.9265). These findings highlight the need to integrate virome and bacteriome analyses with potential diagnostic, prognostic, and therapeutic applications for infectious disease research.