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J Interferon Cytokine Res ; 42(8): 352-368, 2022 08.
Article in English | MEDLINE | ID: covidwho-1992065


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-ß) 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.

COVID-19 , Matrix Metalloproteinases , Transforming Growth Factor beta , Biomarkers , COVID-19/immunology , Cost of Illness , Humans , Matrix Metalloproteinases/immunology , SARS-CoV-2 , Transforming Growth Factor beta/immunology
Sci Adv ; 6(31)2020 07.
Article in English | MEDLINE | ID: covidwho-725277


The outbreak of the highly contagious and deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), has posed a serious threat to public health across the globe, calling for the development of effective diagnostic markers and therapeutics. Here, we report a highly reliable severity diagnostic biomarker, acetylated 676th lysine transforming growth factor-beta-induced protein (TGFBIp K676Ac). TGFBIp K676Ac was consistently elevated in the blood of patients with SARS-CoV-2 pneumonia (n = 113), especially in patients in the intensive care unit (ICU) compared to non-ICU patients. Patients' blood samples showed increased cytokines and lymphopenia, which are exemplary indicators of SARS-CoV-2 pneumonia. Treatment with TGFBIp neutralizing antibodies suppressed the cytokine storm. The increased level of TGFBIp K676Ac in ICU patients suggests the promise of this protein as a reliable severity diagnostic biomarker for severe SARS-CoV-2 disease.

Betacoronavirus/pathogenicity , Coronavirus Infections/diagnosis , Cytokine Release Syndrome/diagnosis , Extracellular Matrix Proteins/immunology , Leukocytes, Mononuclear/immunology , Pneumonia, Viral/diagnosis , Protein Processing, Post-Translational , Respiratory Insufficiency/diagnosis , Transforming Growth Factor beta/immunology , Acetylation , Antibodies, Neutralizing/pharmacology , Betacoronavirus/immunology , Biomarkers/blood , COVID-19 , Case-Control Studies , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Extracellular Matrix Proteins/antagonists & inhibitors , Extracellular Matrix Proteins/genetics , Gene Expression , Humans , Intensive Care Units , Leukocyte Count , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/pathology , Leukocytes, Mononuclear/virology , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Lysine/metabolism , NF-kappa B/genetics , NF-kappa B/immunology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Primary Cell Culture , Prognosis , Respiratory Insufficiency/blood , Respiratory Insufficiency/immunology , Respiratory Insufficiency/pathology , SARS-CoV-2 , Severity of Illness Index , Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/genetics