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

The active lung microbiota landscape of COVID-19 patients through the metatranscriptome data analysis Yang Han Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China http://orcid.org/0000-0002-0034-5848 Zhilong Jia Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China http://orcid.org/0000-0003-2370-5073 Jinlong Shi Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China Weidong Wang Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China Kunlun He Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China

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.
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