Release of Endogenous Chondroitin Sulfate and Heparin as Consequence of Dysregulated Proteolysis in COVID-19

Marco Ruggiero

doi:10.3844/ajisp.2021.40.46

Abstract

Release of Endogenous Chondroitin Sulfate and Heparin as Consequence of Dysregulated Proteolysis in COVID-19

Highlights

Hematologic complications of COVID-19, the disease caused by severe acute respiratory syndromerelated coronavirus 2 (SARS-CoV-2), are of prognostic significance and have been associated with increased mortality
In the context of COVID-19, it can be hypothesized that Chondroitin Sulfate (CS) is released from its association with plasma proteins and peptides by immune responsemediated proteolysis; this might represent a defensive or protective response (Song et al, 2020) since CS, by cause of the high density of negative charges, may block the entry of SARS-CoV-2 into target cells by interacting with the positively charged residues of the virus and, in particular, the TNGTKR, HKNNKS, RSYLTPGDSSSG and QTNSPRRA sequences (Zunaid et al, 2020) that are characterized by hydrophobic residues intercalated in a sequence of positively charged residues (Jaimes et al, 2020)
Endogenous HP is complexed with two categories of plasma proteins; those that are hydrolyzed by sequential addition of proteases in a manner analogous to what observed for CS; and those that are protected by proteases as a result of their association with HP and are removed only by the SDS-PAGE overrun

Summary

Introduction

Hematologic complications of COVID-19, the disease caused by severe acute respiratory syndromerelated coronavirus 2 (SARS-CoV-2), are of prognostic significance and have been associated with increased mortality. These include blood count alterations such as lymphopenia, leukopenia, thrombocytopenia, neutrophilia; hyperferritinemia and elevated lactate dehydrogenase; elevated D-dimer, fibrin degradation products and fibrinogen; and alterations of coagulation such as disseminated intravascular coagulation, thrombosis, hypercoagulability and thrombotic thrombocytopenia (Mina et al, 2020; Castro and Frishman, 2021). Thrombotic thrombocytopenia, is observed in severely ill COVID-19 patients or, alternatively, in medically stable subjects with no anamnesis of pre-existing pro-thrombotic condition, who had received COVID-19 vaccines (Dotan and Shoenfeld, 2021; Aleem and Nadeem, 2021). Direct HP-induced platelet activation occurs independently of PF4 and correlates with lipoprotein lipase activity of HP sub-fractions, but not with their anticoagulant activity (Ruggiero et al, 1984)

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