Genetic Predisposition and Inflammatory Inhibitors in COVID-19: Where Do We Stand?

Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and the resulting coronavirus disease-19 (COVID-19) have led to a global pandemic associated with high fatality rates. COVID-19 primarily manifests in the respiratory system as an acute respiratory distress syndrome following viral entry through the angiotensin-converting enzyme-2 (ACE2) that is present in pulmonary epithelial cells. Central in COVID-19 is the burst of cytokines, known as a cytokine storm, and the subsequent widespread endothelial activation, leading to cardiovascular complications such as myocarditis, arrhythmias, and adverse vascular events, among others. Genetic alterations may play an additive, detrimental role in the clinical course of patients with COVID-19, since gene alterations concerning ACE2, major histocompatibility complex class I, and toll-like receptors may predispose patients to a worse clinical outcome. Since the role of inflammation is quintessential in COVID-19, pharmacologic inhibition of various signaling pathways such as the interleukin-1 and -6, tumor necrosis factor-alpha, interferon gamma, Janus kinase-signal transducer and activator of transcription, and granulocyte-macrophage colony-stimulating factor may ameliorate the prognosis following timely administration. Finally, frequently used, non-specific anti-inflammatory agents such as corticosteroids, statins, colchicine, and macrolides represent additional therapeutic considerations.

Automated summary

SARS-CoV-2 and COVID-19 have caused a global pandemic with high fatality rates. COVID-19 primarily affects the respiratory system through ACE2, leading to a cytokine storm and endothelial activation, resulting in cardiovascular complications. Genetic alterations may worsen the clinical course of COVID-19 patients. Inhibiting inflammatory signaling pathways and using non-specific anti-inflammatory agents could potentially improve prognosis.