EFFECT OF SARS-CoV-2 ON THE COAGULATION CASCADE IN COVID-19 ASSOCIATED COAGULOPATHIES

Background: Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients and particularly the onset of thrombi and ischemia are often associated with a poor prognosis. Although the evidence for an association between SARS-CoV2 infection and coagulopathies is known (Levi et al, 2020), to date the mechanism underlying the alteration of the coagulation cascade in some COVID-19 patients remains misunderstood. Recently, protein S (PROS1), an anticoagulant plasma protein involved in the correct homeostasis of the coagulation cascade, has been described as a potential risk factor for complications related to COVID19 (Lemke et al, 2020) and represents a potential target for PLpro SARS-CoV-2 enzyme proteolysis (Ruzika, 2020). Aim: This study aims to identify peculiar expression patterns in COVID19-associated coagulopathies, to identify possible pharmacological targets, focusing on PROS1 protein alteration. Methods: Thrombotic, arteriosclerotic plaques, venous \ arterial, perivascular fat samples and blood samples were collected from COVID-positive and COVID-negative subject, and from COVID-positive subjects with no coagulopathies. SARS-CoV-2 presence will be evaluated by Real time PCR and by IHC and gene expression, and ELISA analysis will be performed to identify specific expression profiles associated with coagulation imbalances, with particular attention to protein S (PROS1). Results and Conclusions: We reported substantial differences in the activation of the coagulative cascade, and particularly a significant decrease of PROS1, in the COVID-19 cohort experiencing coagulative disorders, in association with SARS-CoV-2 positivity by IHC and real time PCR. These data suggested that, possibly, SARS-CoV-2 associated thrombotic/ischemic events might involve PROS-1 cleavage by viral PLpro, leading to the loss of its anticoagulant function. Basing on this evidence, the use of PLpro inhibitors might be suggest as a therapeutical tool for COVID-19 coagulopathies.