Heme oxygenase-1 (HO-1) cytoprotective pathway: A potential treatment strategy against coronavirus disease 2019 (COVID-19)-induced cytokine storm syndrome

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) requires urgent need for effective treatment. Severe COVID-19 is characterized by a cytokine storm syndrome with subsequent multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS), which may lead to intensive care unit and increased risk of death. While awaiting a vaccine, targeting COVID-19-induced cytokine storm syndrome appears currently as the efficient strategy to reduce the mortality of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The stress-responsive enzyme, heme oxygenase-1 (HO-1) is largely known to protect against inflammatory response in animal models. HO-1 is induced by hemin, a well-tolerated molecule, used for decades in the treatment of acute intermittent porphyria. Experimental studies showed that hemin-induced HO-1 mitigates cytokine storm and lung injury in mouse models of sepsis and renal ischemia-reperfusion injury. Furthermore, HO-1 may also control numerous viral infections by inhibiting virus replication. In this context, we suggest the hypothesis that HO-1 cytoprotective pathway might be a promising target to control SARS-CoV-2 infection and mitigate COVID-19-induced cytokine storm and subsequent ARDS.

Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

“…Accumulating evidence suggest that the major pathology of COVID-19 is characterized not only by acute respiratory distress syndrome, but at the same time excessive systemic inflammatory reaction and coagulopathy [53]. Considering these unique pathology of COVID-19, pharmacological induction of HO-1 in vivo may certainly serve as a potential therapeutic target to overcome the severe complication of COVID-19 [54][55][56].…”

Letter to the Editor: Boron enhances the antiviral activity of the curcumin against SARS-CoV-2

“…Various compelling evidence indicate a possible role for hemin-induced HO-1 as a therapy strategy against the SARS-CoV-2-induced cytokine storm syndrome. Hemin-induced HO-1 might be a harmless, novel, and promising approach for controlling SARS-CoV-2 infection and limiting cytokine [ 38 ].…”

Between two storms, vasoactive peptides or bradykinin underlie severity of COVID‐19?

“…KARAMYAN they are fundamentally associated with progression of the disease and mortality of COVID-19 patients (Mahmudpour et al, 2020;Rossi et al, 2020).…”

“…Hence, it is natural that researchers around the world have used various approaches to explore and understand the COVID‐19 morbidity (Sparks et al, 2020; Wang et al, 2020). Among these, arguably most notable are studies focusing on inflammatory mechanisms, pro‐inflammatory cytokines, and “cytokine storm,” since they are fundamentally associated with progression of the disease and mortality of COVID‐19 patients (Mahmudpour et al, 2020; Rossi et al, 2020).…”