Internal medicine

Pathology

ARDS

Disease

Pathogenesis

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Biology

Pandemic

Immunology

Lung

Inflammation

Coronavirus

Pneumonia

Acute respiratory distress

Medicine

Immune system

Diffuse alveolar damage

Nature Reviews Microbiology

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. In this Review, Lamers and Haagmans explore recent clinical and experimental advances in understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis, interactions with host cells and the involvement of the immune system in the development of severe disease. Specifically, they focus on mechanisms underlying the development of COVID-19-associated acute respiratory distress syndrome.

SARS-CoV-2 pathogenesis