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 sarscov- 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 sarscov- 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