Transcriptome analysis reveals increased abundance and diversity of opportunistic fungal pathogens in nasopharyngeal tract of COVID-19 patients

Abstract

We previously reported that SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiomes (bacteria, archaea and commensal respiratory viruses) with inclusion of pathobionts. This study aimed to assess the possible changes in the abundance and diversity of resident mycobiome in the nasopharyngeal tract (NT) of humans due to SARS-CoV-2 infections. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 = 8, Recovered = 7, and Healthy = 7) were collected for RNA-sequencing followed by taxonomic profiling of mycobiome. Our analyses indicate that SARS-CoV-2 infection significantly increased (p < 0.05, Wilcoxon test) the population and diversity of fungi in the NT with inclusion of a high proportion of opportunistic pathogens. We detected 863 fungal species including 533, 445, and 188 species in COVID-19, Recovered, and Healthy individuals, respectively that indicate a distinct mycobiome dysbiosis due to the SARS-CoV-2 infection. Remarkably, 37% of the fungal species were exclusively associated with SARS-CoV-2 infection, where S. cerevisiae (88.62%) and Phaffia rhodozyma (10.30%) were two top abundant species. Likewise, Recovered humans NT samples were predominated by Aspergillus penicillioides (36.64%), A. keveii (23.36%), A. oryzae (10.05%) and A. pseudoglaucus (4.42%). Conversely, Nannochloropsis oceanica (47.93%), Saccharomyces pastorianus (34.42%), and S. cerevisiae (2.80%) were the top abundant fungal species in Healthy controls nasal swabs. Importantly, 16% commensal fungal species found in the Healthy controls were not detected in either COVID-19 patients or when they were cured from COVID-19 (Recovered). We also detected several altered metabolic pathways correlated with the dysbiosis of fungal mycobiota in COVID-19 patients. Our results suggest that SARS-CoV-2 infection causes significant dysbiosis of mycobiome and related metabolic functions possibly play a determining role in the progression of SARS-CoV-2 pathogenesis. These findings might be helpful for developing mycobiome-based diagnostics, and also devising appropriate therapeutic regimens including antifungal drugs for prevention and control of concurrent fungal coinfections in COVID-19 patients.