SARS‑CoV‑2 Associated Shifts in the Upper Respiratory Tract Mycobiome in Non-hospitalized Cases

SARS‑CoV‑2 infection is associated with marked changes of the upper respiratory tract mycobiome. URT mycobiome Changes in non-hospitalized patients however, remains poorly defined. We performed shotgun metagenomic sequencing of 95 upper respiratory tract swab samples from 48 symptomatic SARS‑CoV‑2-positive individuals and 47 healthy controls from central India. Fungal diversity and community structure were compared using alpha- and beta-diversity analyses, while differential taxa were identified using prevalence-based testing and a Directional Significance Score (DSS). SARS‑CoV‑2-positive samples showed significantly higher fungal alpha diversity than controls, with increased Shannon diversity (p = 0.000319) and Simpson diversity (p = 0.017). Beta-diversity analysis showed significant separation between groups for both Bray-Curtis and Jaccard distances (PERMANOVA p = 0.001), with significant dispersion effects as well (PERMDISP p = 0.001). DSS analysis showed certain fungal taxa associated with the SARS-CoV-2 group, including enrichment of Candida orthopsilosis, Malassezia furfur, Aspergillus glaucus, Aspergillus terreus, and Aspergillus niger, while Malassezia arunalokei, Aspergillus chevalieri, and Aspergillus sydowii were enriched in controls. These findings indicate that SARS‑CoV‑2 infection is associated with URT mycobiome dysbiosis and enrichment of clinically relevant opportunistic fungi in community cases.