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COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure

COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure
Monia Marchetti
Hematology Department, Az Osp SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
COVID-19 pandemia is a major health emergency causing hundreds of deaths worldwide. The high reported morbidity has been related to hypoxia and inflammation leading to endothelial dysfunction and aberrant coagulation in small and large vessels. This review addresses some of the pathways leading to endothelial derangement, such as complement, HIF-1α, and ABL tyrosine kinases. This review also highlights potential targets for prevention and therapy of COVID-19-related organ damage and discusses the role of marketed drugs, such as eculizumab and imatinib, as suitable candidates for clinical trials.
Keywords: COVID-19; Complement; Eculizumab; Endothelium; HIF-1-alpha; Imatinib; SARS-CoV; Thrombosis.
Several pathways have been identified as possible drivers in the pathogenesis of SARS-CoV-2: some pathways, such as the complement, may be targeted by available drugs, while some others are orphan of specific therapies, such as HIF-1α and HIF-2α. Several drugs currently marketed for blood diseases, such as imatinib, ruxolitinib, heparins, tocilizumab, and eculizumab, are currently being tested for patients with COVID-19 symptoms. Hematologists, who are expert on such drugs, are therefore called into multidisciplinary teams for managing patient selection and therapy monitoring. While awaiting vaccines and effective antiviral therapies, their expertise needs to be combined with the updated evidence on the pathogenesis of COVID-19, as they have the chance to contribute to amelioration of patient outcomes. Appropriate trial designs still need to be developed in order to address some fundamental issues, such as COVID-19 patient stratification and testing of multiple drugs. Furthermore, trials are challenged by heterogeneous support therapies for COVID-19 and partial non-comparability of patients belonging to different clinical centers. Nevertheless, most of the above cited candidate drugs have a favorable safety profile, especially in the short term, and are promising tools for defeating COVID-19.