COVID-19: In the Eye of the Cytokine Storm

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This cytokine storm produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities. In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1, and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases and conditions often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.
RR acknowledges funding from IdISBa/Impost turisme sostenible/Govern de les Illes Balears (Agencia d'Estrategia Turistica de les Illes Balears-Govern de les Illes Balears) through a Radix fellowship. MG-F acknowledges funding by the Miguel Servet Program (MS19/00201), Instituto de Salud Carlos III (ISCIII), Madrid. Figures were created with images from Canva (www.canva.com) under Free Media License Agreement.