COVID-19 Lung Injury: Unique and Familiar Aspects of Pathophysiology

Acute lung injury (ALI), diagnosed clinically as acute respiratory distress syndrome (ARDS), refers to a spectrum of acute inflammatory processes culminating in increased permeability of the pulmonary alveolar–capillary barrier and impaired gas exchange. The pandemic caused by the novel coronavirus, SARS-CoV-2, has raised questions as to the similarities and differences between COVID-19 lung injury and ALI of other etiologies. This review summarizes current knowledge regarding the pathophysiology of ALI and COVID-19 lung injury and draws comparisons between the latter and other infectious etiologies of ALI. Indeed, severe COVID-19 is characterized by a unique array of disease mechanisms including suppression of interferon responses, widespread inflammasome activation, altered leukocyte phenotypes, and hyperactive thrombotic activity. Moreover, these mechanisms manifest as a unique clinical progression, which further differentiates COVID-19 from other viral respiratory pathogens such as SARS, MERS, and influenza. These unique features of COVID-19 pathophysiology bear important implications for current and future therapeutic strategies.