Acute response to SARS-CoV-2 infection in alveolar and vascular compartments.

SARS-CoV-2 by utilizing ACE2 and TMPRSS2 invades epithelial layers to enter in alveolar compartment. Infected cell then releases DAMPs and PAMP molecules to alert immune system. While antigen presenting cells process and present SARS-CoV-2 antigen to CD4+ T cells, activation of innate and adaptive immune systems and production of inflammatory cytokines such as MCP-1, IL-1β, IL-6, and TNFα take place. These inflammatory monocytes cause production and activation of tissue factors that induce endothelial dysfunction. EC inflammation and cell death disrupts endothelial barrier and result in vascular leakage. Vascular neutrophilic inflammation can mediate platelet activation via proinflammatory cytokines to establish immune thrombosis. NET formation can contribute to prothrombotic state in hyperinflammation. Created with BioRender.com. ACE2, angiotensin converting enzyme 2; DAMP, damage-associated molecular pattern; IL, interleukin; PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; TMPRSS2, transmembrane serine protease 2; TNF, tumor necrosis factor.