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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.

SUBMITTER: Rossi M

PROVIDER: S-EPMC7467863 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Rossi Maxime M Piagnerelli Michael M Van Meerhaeghe Alain A Zouaoui Boudjeltia Karim K

Medical hypotheses 20200903

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 syndrom ...[more]

PMID: 33254548

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Project description:BackgroundCytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes.Research questionDo immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)?Study design and methodsWe conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, > 700 ng/mL; C-reactive protein (CRP), > 30 mg/dL; or lactate dehydrogenase (LDH), > 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-IL-6 antibody (tocilizumab), or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality.ResultsFive thousand seven hundred seventy-six patients met the inclusion criteria. The most common comorbidities were hypertension (44%-59%), diabetes (32%-46%), and cardiovascular disease (5%-14%). Patients most frequently met criteria with high LDH (76.2%) alone or in combination, followed by ferritin (63.2%) and CRP (8.4%). More than 80% of patients showed an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination showed lower mortality compared with patients receiving standard-of-care (SoC) treatment (hazard ratio [HR], 0.44; 95% CI, 0.35-0.55; P < .0001) and with patients treated with corticosteroids alone (HR, 0.66; 95% CI, 0.53-0.83; P = .004) or in combination with anakinra (HR, 0.64; 95% CI, 0.50-0.81; P = .003). Corticosteroids when administered alone (HR, 0.66; 95% CI, 0.57-0.76; P < .0001) or in combination with tocilizumab (HR, 0.43; 95% CI, 0.35-0.55; P < .0001) or anakinra (HR, 0.68; 95% CI, 0.57-0.81; P < .0001) improved hospital survival compared with SoC treatment.InterpretationThe combination of corticosteroids with tocilizumab showed superior survival outcome when compared with SoC treatment as well as treatment with corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with CCS compared with patients receiving SoC treatment.

Dataset Information

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

Publications

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

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