Pathophysiology of COVID-19: Mechanisms Underlying Disease Severity and Progression

Abstract

The global epidemiology of coronavirus disease 2019 (COVID-19) suggests a wide spectrum of clinical severity, ranging from asymptomatic to fatal. Although the clinical and laboratory characteristics of COVID-19 patients have been well characterized, the pathophysiological mechanisms underlying disease severity and progression remain unclear. This review highlights key mechanisms that have been proposed to contribute to COVID-19 progression from viral entry to multisystem organ failure, as well as the central role of the immune response in successful viral clearance or progression to death.

Keywords: COVID-19; coagulation; cytokine storm; multisystem organ failure; pathophysiolog.

FIGURE 1.

Characterization of key events in COVID-19 disease pathophysiological progression The dark blue shading indicates physiological viral host response over time, and the dark red shading indicates pathogenic hyperinflammatory host response over time. Figure adapted from Ref. , with permission from the Journal of Heart and Lung Transplantation.

FIGURE 2.

Physiological host immune response to SARS-CoV-2 infection 1: SARS-CoV-2 enters alveolar epithelial cells by binding to angiotensin converting enzyme 2 (ACE2) through surface spike (S) protein mediated by transmembrane serine protease 2 (TMPRSS2). 2: pulmonary recruitment of macrophages and dendritic cells in response to chemokine and cytokine release (early phase). 3: direct viral infection of pulmonary macrophages and dendritic cells causes expression of several proinflammatory cytokines and chemokines. 4: dendritic cells phagocytose virus in the lungs, migrate to secondary lymphoid organs, and activate antigen-specific T cells, which travel to the lungs and destroy virally infected alveolar cells.

FIGURE 3.

Laboratory/clinical profile and key potential mechanisms underlying extrapulmonary manifestations observed in severe COVID-19 patients NT-proBNP, NH₂-terminal-proB-type natriuretic peptide; ALT, alanine aminotransferase; AST, aspartate aminotransferase; aPTT, activated partial thromboplastin time; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; ESR, erythrocyte sedimentation rate.