Possible Role of Matrix Metalloproteinases and TGF-β in COVID-19 Severity and Sequelae

The costs of coronavirus disease 2019 (COVID-19) are devastating. With millions of deaths worldwide, specific serological biomarkers, antiviral agents, and novel therapies are urgently required to reduce the disease burden. For these purposes, a profound understanding of the pathobiology of COVID-19 is mandatory. Notably, the study of immunity against other respiratory infections has generated reference knowledge to comprehend the paradox of the COVID-19 pathogenesis. Past studies point to a complex interplay between cytokines and other factors mediating wound healing and extracellular matrix (ECM) remodeling that results in exacerbated inflammation, tissue injury, severe manifestations, and a sequela of respiratory infections. This review provides an overview of the immunological process elicited after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Also, we analyzed available data about the participation of matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-beta) in immune responses of the lungs. Furthermore, we discuss their possible implications in severe COVID-19 and sequela, including pulmonary fibrosis, and remark on the potential of these molecules as biomarkers for diagnosis, prognosis, and treatment of convalescent COVID-19 patients. Our review provides a theoretical framework for future research aimed to discover molecular hallmarks that, combined with clinical features, could serve as therapeutic targets and reliable biomarkers of the different clinical forms of COVID-19, including convalescence.

Automated summary

The costs of COVID-19 are devastating and there is an urgent need for serological biomarkers, antiviral agents, and novel therapies. Previous studies on immunity against other respiratory infections provide reference knowledge to understand the pathogenesis of COVID-19. This review discusses the immune responses and the involvement of matrix metalloproteinases and transforming growth factor-beta in the lungs. Furthermore, it explores the potential implications of these molecules as biomarkers for diagnosis, prognosis, and treatment of COVID-19 patients, including those in the convalescent phase.