Weathering the Cytokine Storm in COVID-19: Therapeutic Implications

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis.

Summary: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.

Keywords: COVID-19; Cytokine storm; Therapy.

Fig. 1

Cytokine storm consequent to SARS-CoV2 infection is emerging as the main mechanism leading to ARDS and MOF in COVID-19. Identification of patients with a hyperinflammatory response through cytokine profiling could direct the choice of a specific anticytokine drug or even combined/sequential regimens; in selected cases, implementation of broad-spectrum anti-inflammatory therapies, such as IVIg and blood purification, could be considered. AAK1, adaptor-associated protein kinase 1; CCR5, C-C chemokine receptor type 5; T CD, T-cell cluster of differentiation; FGF, fibroblast growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; G-CSF, granulocyte colony-stimulating factor; MIP1, macrophage inflammatory protein 1.