atients with COVID-19 exhibit a broad spectrum of disease progression, with 81% showing mild, moderate or no symptoms; 14% showing severe symptoms; and 5% experiencing critical disease with high mortality risk 1 . The risk of developing severe or critical disease has been associated with advanced age 1,2 , comorbidities 1,2 , hyperactivation of the immune system 3,4 , sex 1,2 and other factors. However, an understanding of these risk factors at the molecular and cellular levels is in its infancy.In this study, we investigated the immune response in patients with COVID-19 by single-cell RNA sequencing (scRNA-seq) of nasopharyngeal and bronchial samples to identify molecular correlates of disease severity. Two recent studies applied scRNA-seq to bronchioalveolar lavage fluid samples from patients with COVID-19 and provide an extensive characterization of the inflammatory immune phenotype in the lower respiratory tract 5,6 . However, SARS-CoV-2 and other coronaviruses infect and replicate in both COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis
The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.
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