Yan Leyfman

"Cancer and COVID-19: A Hypoxic Immunological Paradigm"

Yan Leyfman, Timothy K. Erick, Sandeep S. Reddy, Pushpa Sharma

Coronavirus disease 2019 (COVID-19), a respiratory illness caused by betacoronavirus SARS-CoV-2, has broad clinical presentations ranging from asymptomatic to fatal outcomes. Studies have demonstrated that patients with severe symptoms, and uncontrolled inflammatory state have poor prognosis. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation, and hypoxia induced cellular metabolic alterations. Hypoxia is also common in malignant tumours, where it alters cancer cell metabolism, and contributes to therapeutic resistance in various cancers. Therefore, we propose a potential synergism between influenza virus and SARS-CoV-2, which we have termed “COVI-Flu.” In this model, co-infection with both viruses may result in increased IL-6 production resulting in enhanced systemic injury as compared to either virus alone. Increased systemic injury via viral synergism is likely further worsened in the presence of malignancy. Currently, there are no available safe and effective therapeutic interventions against SARS-CoV-2 or the potential COVI-Flu. Based on the similarities between the disease mechanisms of SARS-CoV-2 and influenza virus, we propose the use of combination therapies that can control the systemic inflammation induced by both viruses. One approach is the use of a cellular therapy that has yielded promising preliminary efficacy in COVID-19 patients. Looking forward, we foresee combinational therapies targeted at multiple steps within the direct and indirect pathways to hinder direct viral injury, increased IL-6 release, and systemic inflammation being used that can better thwart the virus’s heterogeneity and mutational adaptations. In anticipation of the potential COVI-Flu pandemic, we propose that enacting a flu immunization program can provide some protection against the synergism of the two viruses.