ABSTRACT
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.
ABSTRACT
Background The mortality of COVID-19 differs between countries and regions. By now, reports on COVID-19 are largely focused on first-generation cases. This study aimed to clarify the clinical characteristics of imported and second-generation cases. Methods This retrospective, multicenter cohort study included 134 confirmed COVID-19 cases from 9 cities outside Wuhan. Epidemiological, clinical and outcome data were extracted from medical records and were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. Results 34.3% of the 134 patients were severe cases, and 11.2% had complications. As of March 7, 2020, 91.8% patients were discharged and one patient (0.7%) died. The median age was 46 years. The median interval from symptom onset to hospital admission was 4.5 (IQR 3-7) days. The median lymphocyte count was 1.1*109/L. Age, lymphocyte count, CRP, ESR, DBIL, LDH, HBDH showed difference between severe and no-severe cases (all P<0.05). Baseline lymphocyte count was higher in the survived patients than in the non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The IL-6 level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest CT images in 51.5% of the pneumonia cases. Conclusion Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.
Subject(s)
Pneumonia , Death , COVID-19 , Pulmonary FibrosisABSTRACT
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.