Background: Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients with a poor prognosis or long-COVID syndrome, possibly due to the persistence of SARS-CoV-2 infection in the cardiovascular system. To date, the mechanism underlying the alteration of the coagulation cascade in COVID-19 patients remains misunderstood and the anticoagulant protein S (PROS1) has been described as a potential risk factor for complications related to COVID-19, due to PLpro SARS-CoV-2 enzyme proteolysis. Methods: Biopsies and blood samples were collected from SARS-CoV-2 positive and negative swab test subjects with coagulopathies (peripheral arterial thrombosis), and SARS-CoV-2 presence, ACE2 and CD147 expression, and plasmatic levels of PROS1 were evaluated. Results: We reported a significant decrease of plasmatic PROS1 in the coagulopathic SARS-CoV-2 swab positive cohort, in association with SARS-CoV-2 in situ infection and CD147 peculiar expression. These data suggested that SARS-CoV-2 associated thrombotic/ischemic events might involve PROS1 cleavage by viral PLpro directly in the site of infection, leading to the loss of its anticoagulant function. Conclusions: Based on this evidence, the identification of predisposing factors, such as CD147 increased expression, and the use of PLpro inhibitors to preserve PROS1 function, might be useful for COVID-19 coagulopathies management.

In Situ Endothelial SARS-CoV-2 Presence and PROS1 Plasma Levels Alteration in SARS-CoV-2-Associated Coagulopathies

Baroni, Marcello
Co-primo
;
Beltrami, Silvia
Co-primo
;
Schiuma, Giovanna;Ferraresi, Paolo;Rizzo, Sabrina;Passaro, Angelina;Molina, Juana Maria Sanz;Rizzo, Roberta
;
Di Luca, Dario
Penultimo
;
Bortolotti, Daria
Ultimo
2024

Abstract

Background: Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients with a poor prognosis or long-COVID syndrome, possibly due to the persistence of SARS-CoV-2 infection in the cardiovascular system. To date, the mechanism underlying the alteration of the coagulation cascade in COVID-19 patients remains misunderstood and the anticoagulant protein S (PROS1) has been described as a potential risk factor for complications related to COVID-19, due to PLpro SARS-CoV-2 enzyme proteolysis. Methods: Biopsies and blood samples were collected from SARS-CoV-2 positive and negative swab test subjects with coagulopathies (peripheral arterial thrombosis), and SARS-CoV-2 presence, ACE2 and CD147 expression, and plasmatic levels of PROS1 were evaluated. Results: We reported a significant decrease of plasmatic PROS1 in the coagulopathic SARS-CoV-2 swab positive cohort, in association with SARS-CoV-2 in situ infection and CD147 peculiar expression. These data suggested that SARS-CoV-2 associated thrombotic/ischemic events might involve PROS1 cleavage by viral PLpro directly in the site of infection, leading to the loss of its anticoagulant function. Conclusions: Based on this evidence, the identification of predisposing factors, such as CD147 increased expression, and the use of PLpro inhibitors to preserve PROS1 function, might be useful for COVID-19 coagulopathies management.
2024
Baroni, Marcello; Beltrami, Silvia; Schiuma, Giovanna; Ferraresi, Paolo; Rizzo, Sabrina; Passaro, Angelina; Molina, Juana Maria Sanz; Rizzo, Roberta; ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2539110
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