Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Efectos Adversos a Largo Plazo , Pruebas de Función Respiratoria , Insuficiencia Respiratoria , COVID-19/complicaciones , COVID-19/fisiopatología , COVID-19/terapia , Comorbilidad , Convalecencia , Femenino , Alemania/epidemiología , Humanos , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/epidemiología , Efectos Adversos a Largo Plazo/etiología , Efectos Adversos a Largo Plazo/fisiopatología , Masculino , Persona de Mediana Edad , Debilidad Muscular/etiología , Debilidad Muscular/fisiopatología , Pruebas de Función Respiratoria/métodos , Pruebas de Función Respiratoria/estadística & datos numéricos , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
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.