The active lung microbiota landscape of COVID-19 patients (preprint)

With the outbreak of COVID-19 causing by 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 contributes to COVID-19 complications. 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. The infection of SARS-CoV-2 could deeply change the lung microbiota, evidenced by the -diversity, {beta}-diversity and species composition analysis based on bacterial microbiota and virome. Pathogens (such as Klebsiella oxytoca causing pneumonia as well), immunomodulatory probiotics (such as 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 only existed in the healthy group. Our study provides insight into the active microbiota in the lungs of COVID-19 patients and will contribute to the understanding of the infection mechanism of SARS-CoV-2 and the treatment of the disease and complications.

Heightened innate immune responses in the respiratory tract of COVID-19 2 patients

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV44 2 infection has posed a severe threat to global public health. It is unclear how the human 45 immune system responds to this infection. Here, we used metatranscriptomic 46 sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight 47 COVID-19 cases. The expression of proinflammatory genes, especially chemokines, 48 was markedly elevated in COVID-19 cases compared to community-acquired 49 pneumonia patients and healthy controls,suggesting that SARS-CoV-2 infection causes 50 hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate 51 interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous 52 IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potential, with 53 overrepresentation of genes involved in inflammation. The transcriptome data was also 54 used to estimate immune cell populations, revealing increases in activated dendritic 55 cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection 3 56 could further our understanding of disease pathogenesis and point towards antiviral 57 strategies.

Overly Exuberant Innate Immune Response to SARS-CoV-2 Infection (preprint)

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection has posed a severe threat to global public health. It is unclear how the human immune system responds to the virus infection. Here, we profiled the immune transcriptome signatures by metatranscriptome sequencing for the bronchoalveolar lavage fluid from eight COVID-19 cases. The expression of the proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases as compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection caused hypercytokinemia. Contrasting with SARS-CoV, which is thought to induce inadequate interferon (IFN) response, SARS-CoV-2 robustly triggered the expression of myriad IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potentials, characterized by the overrepresentation of genes involved in inflammation. Collectively, we profiled the molecular signatures of the host response to SARS-CoV-2 infection, which could help to understand the disease pathogenesis and provided clues for tailored antiviral strategies, such as IFN therapy.