The active lung microbiota landscape of COVID-19 patients through the metatranscriptome data analysis

Introduction: With the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the interaction between the host and SARS-CoV-2 was widely studied. However, it is unclear whether and how SARS-CoV-2 infection affects lung microflora, which contribute to COVID-19 complications. Methods: Here, we analyzed the metatranscriptomic data of bronchoalveolar lavage fluid (BALF) of 19 COVID-19 patients and 23 healthy controls from 6 independent projects and detailed the active microbiota landscape in both healthy individuals and COVID-19 patients. Results: The infection of SARS-CoV-2 could deeply change the lung microbiota, evidenced by the α-diversity, β-diversity, and species composition analysis based on bacterial microbiota and virome. Pathogens (e.g., Klebsiella oxytoca causing pneumonia as well), immunomodulatory probiotics (e.g., lactic acid bacteria and Faecalibacterium prausnitzii, a butyrate producer), and Tobacco mosaic virus (TMV) were enriched in the COVID-19 group, suggesting a severe microbiota dysbiosis. The significant correlation between Rothia mucilaginosa, TMV, and SARS-CoV-2 revealed drastic inflammatory battles between the host, SARS-CoV-2, and other microbes in the lungs. Notably, TMV only existed in the COVID-19 group, while human respirovirus 3 (HRV 3) only existed in the healthy group. Our study provides insights into the active microbiota in the lungs of COVID-19 patients and would contribute to the understanding of the infection mechanism of SARS-CoV-2 and the treatment of the disease and complications. Conclusion: SARS-COV-2 infection deeply altered the lung microbiota of COVID-19 patients. The enrichment of several other pathogens, immunomodulatory probiotics (lactic acid or butyrate producers), and TMV in the COVID-19 group suggests a complex and active lung microbiota disorder.