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

Inflammasome formation in the lungs of patients with fatal COVID-19

“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a clinical syndrome in humans referred to as coronavirus disease 2019 (COVID-19) that ranges from mild self-limiting rhinopharyngitis to severe acute respiratory distress syndrome (ARDS) which can be fatal [1]. The mechanisms by which ARDS ensues are incompletely understood, but is considered to be related to an inappropriate release of pro-inflammatory cytokines [2]. Elevated levels of pro-inflammatory mediators predict worse outcomes and identify patients in the hyper-inflammatory stage [1,2], hence the need to better understand the inflammatory response.…”

“…The mechanisms by which ARDS ensues are incompletely understood, but is considered to be related to an inappropriate release of pro-inflammatory cytokines [2]. Elevated levels of pro-inflammatory mediators predict worse outcomes and identify patients in the hyper-inflammatory stage [1,2], hence the need to better understand the inflammatory response.…”

Possible role of tryptophan and melatonin in COVID-19

“…Kinase inhibitors are also being tried. 4 Until the development of vaccines and better therapeutics, there is an urgent need for strategies to control respiratory infection and to boost immune functions for patients suffering from COVID-19. 5,6 L-tryptophan (Trp), an essential amino acid, is the precursor of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), which promotes a sense of well-being and "happiness", and plays a role in preventing mood disorders.…”

“…Kinase inhibitors are also being tried. 4 Until the development of vaccines and better therapeutics, there is an urgent need for strategies to control respiratory infection and to boost immune functions for patients suffering from COVID-19. 5 , 6 …”

COVID-19 and Sodium-Glucose Cotransporter 2 Inhibitors: No Fear to Attempt?

“…The rationale for these trials is that SGLT-2is not only improve heart failure and renal function in type 2 DM [7], but they also appear to reduce inflammation, hypoxia and excess cytokine release [10,11]. Importantly, the latter is known to play a pivotal role in adverse outcomes in COVID-19 [12,13]. In DARE-19 (900 participants), inclusion criteria are hospitalisation for mild-to-moder-…”