SARS-CoV-2 pathogenesis

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating pandemic. Although most people infected with SARS-CoV-2 develop a mild to moderate disease with virus replication restricted mainly to the upper airways, some progress to having a life-threatening pneumonia. In this Review, we explore recent clinical and experimental advances regarding SARS-CoV-2 pathophysiology and discuss potential mechanisms behind SARS-CoV-2-associated acute respiratory distress syndrome (ARDS), specifically focusing on new insights obtained using novel technologies such as single-cell omics, organoid infection models and CRISPR screens. We describe how SARS-CoV-2 may infect the lower respiratory tract and cause alveolar damage as a result of dysfunctional immune responses. We discuss how this may lead to the induction of a 'leaky state' of both the epithelium and the endothelium, promoting inflammation and coagulation, while an influx of immune cells leads to overexuberant inflammatory responses and immunopathology. Finally, we highlight how these findings may aid the development of new therapeutic interventions against COVID-19.