Shedding Light on COVID-19: ADAM17 the Missing Link?. (May 2021)

• Record Type: Journal Article
• Authors: Schreiber, Brittany; Patel, Ankit; Verma, Ashish
• Is Part Of: American journal of therapeutics. Volume 28:Number 3(2021)
• Publication Date: 2021-05
• Subjects: COVID-19 -- ADAM17 -- ACE2 and therapeutic; Chemotherapy -- Periodicals; Pharmacology -- Periodicals; 615.58
• DOI: 10.1097/MJT.0000000000001226
• Languages: English
• ISSNs: 1075-2765

Abstract

Abstract : Background: Coronavirus disease 2019 (COVID-19) is a rapidly expanding global health crisis. A disintegrin and metalloproteinase 17 (ADAM17), an ectodomain sheddase, is a key component of ACE2 modulation and plays a complex role in inflammation and immunosurveillance. Areas of Uncertainty: Much remains unknown regarding the immunopathogenesis of COVID-19, including how the virus affects ADAM17 expression, activity, and regulation. Search Strategy: Three electronic databases (MEDLINE through PubMed, Embase through Ovid, and Google Scholar) were searched to identify articles relevant to ADAM17 and severe acute respiratory syndrome coronavirus 1 and 2. Relevant articles published from January 1, 2005, to April 30, 2020, were selected, and reference lists were screened and cross-referenced. We also searched preprint studies on medRxiv and bioRxiv given the rapidly evolving data on COVID-19 SARS-CoV-2. Therapeutic Opinion: Infection with SARS-CoV-2 may lead to an increase in ADAM17 sheddase activity contributing to an exuberant macrophage-predominant inflammatory response and diminished immunosurveillance capacity for viral clearance. Emerging data suggest severe lung injury in COVID-19 is associated with higher levels of TNF-α and IL-6, T-cell lymphopenia and exhaustion, hypercoagulability, and a macrophage-predominant immune response. This clinical picture is consistent with dysregulation of many of the molecular pathways in which ADAM17 participates. Conclusions: Elucidation of the role of ADAM17 in COVID-19 may identify novel molecular targets for drug development and therapeutic repurposement.