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Severe acute respiratory syndrome coronavirus 2 has spreadrapidly around theglobe. However, despite its high pathogenicity and transmissibility, the severity of theassociated disease, COVID-19, varies widely. While the prognosis is favorable in mostpatients, critical illness, manifested by respiratory distress, thromboembolism, shock,and multi-organ failure, has been reported in about 5% of cases. Several studies haveassociated poor COVID-19 outcomes with the exhaustion of natural killer cells andcytotoxic T cells, lymphopenia, and elevated serum levels of D-dimer. In this article,we propose a common pathophysiological denominator for these negative prognosticmarkers, endogenous, angiotensin II toxicity. We hypothesize that, like in avian influenza,the outlook of COVID-19 is negatively correlated with the intracellular accumulation ofangiotensin II promoted by the viral blockade of its degrading enzyme receptors. Inthis model, upregulated angiotensin II causes premature vascular senescence, leadingto dysfunctional coagulation, and immunity. We further hypothesize that angiotensin IIblockers and immune checkpoint inhibitors may be salutary for COVID-19 patients withcritical illness by reversing both the clotting and immune defects (Graphical Abstract).


© 2020 Sfera, Osorio, Jafri, Diaz and Campo Maldonado. Original published version available at

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Publication Title

Frontiers in Immunology



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Mentor/PI Department

Immunology and Microbiology



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