Pathophysiology

SARS-CoV-2 enters the human body via interaction with angiotensin-converting enzyme 2 (ACE-2) receptors and releases its RNA inside epithelial cells, where it replicates. From the nasal epithelial cells, SARS-CoV-2 spreads to the alveoli of the lungs [7]. Endothelial injury is a key consequential pathologic event, leading to multiorgan failure. Compromise of vascular integrity of the alveoli results in pulmonary edema, disseminated intravascular coagulation, pulmonary ischemia, hypoxic respiratory failure, and progressive lung damage [8]. After SARS-CoV-2 invades epithelial cells by binding with ACE-2 receptors, localized inflammation, endothelial activation, tissue damage, and dysregulated cytokine release begins. Cytokine storm starts with secretion of vascular endothelial growth factor, monocyte chemoattractant protein-1, IL-1, IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α, interferon-γ, and reduced E-cadherin expression on epithelial cells [9–11]. High levels of cytokines potentiate inflammation, epithelial and endothelial cell dysfunction, vasodilation of the capillary bed resulting in acute respiratory distress syndrome (ARDS), multiorgan failure, and death. Increased levels of cytokines and chemokines are associated with severity of COVID-19. Therapeutic interventions to normalize the vasculature include use of anti-inflammatory drugs, ACE inhibitors, and anti-cytokine drugs [12]. Cytokine inhibitors are being used to contain the cytokine storm effectively [12].