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Publications

Journal Article Review Epublish

PubMed: 40799952 DOI: 10.2147/IDR.S541205

COVID-19: A Disease Driven by Protease/Antiprotease Imbalance? A Specific Review Five Years into the Pandemic.

Infect Drug Resist 18:3967-3975

Authors: Pierpaolo Di Micco, Carmine Siniscalchi, Egidio Imbalzano, Vincenzo Russo, Giuseppe Camporese, Corrado Lodigiani, Tiziana Meschi, Alessandro Perrella

Affiliations

  • UOC Medicina Interna, AFO Medica, P.O. Santa Maria delle Grazie, Pozzuoli (NA), ASL Napoli 2 Nord, CAP 80076, Italy.
  • Internal Medicine Department, Parma University Hospital, Parma, Italy.
  • Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
  • Department of Cardiology, Vanvitelli University of Naples, Naples, Italy.
  • Department of Internal Medicine DIMED, Padua University Hospital, Padua, Italy.
  • Department of Internal Medicine, Humanitas Hospital Milano, Milano, Italy.
  • UOC Emerging Infectious Disease and High Contagiousness AORN Ospedale dei Colli-PO D. Cotugno, Naples, Italy.

Abstract

COVID-19, caused by SARS-CoV-2, has profoundly impacted global health since late 2019. Beyond respiratory complications, the disease involves systemic manifestations driven by immune dysregulation, inflammation, and coagulopathy. Among the many mechanisms implicated in severe disease, a growing body of evidence suggests a central role for the imbalance between proteases and antiproteases. This review examines how dysregulated protease activity contributes to viral entry, cytokine activation, vascular injury, and thrombosis. We focus on the integration of proteolytic systems such as the renin-angiotensin system, coagulation cascade, and neutrophil extracellular traps with established pathways like endothelial dysfunction and immune hyperactivation. Furthermore, we highlight therapeutic strategies aimed at restoring proteolytic balance and discuss the potential relevance of this paradigm in the management of long COVID.

MeSH

Fibrinolysis, Cytokine Release Syndrome, Biomarkers, Thrombophilia, Covid-19, Peptide Hydrolases, Pandemics, Protease Inhibitors, Serpins