ReviewFrontiers in immunology2020
ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19.
Review in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
186 citing papers in PubMed, 4 syntheses or guidelines pooled it, 270 citations in OpenAlex.
- A systematic review on impact of SARS-CoV-2 infection.Microbiological research · 2023Pooled it
- Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2.Journal of translational medicine · 2023Pooled it
- Pooled it
- COVID-19 pandemic: insights into molecular mechanisms leading to sex-based differences in patient outcomes.Expert reviews in molecular medicine · 2021Pooled it
- Spike 1 protein of SARS-CoV-2 induces endothelial inflammation and vascular dysfunction through interferon ISG15-dependent mechanisms.Cardiovascular research · 2026Article
- Significance and Usefulness of High-Resolution 24-h Electrocardiographic Parameters in Patients With Coronavirus Disease 2019 After Admission: A Prospective Cohort Study.Journal of arrhythmia · 2026Article
- The balance between classical and alternative renin-angiotensin system in ARDS: a narrative review.Journal of intensive care · 2026Review
- Fecal ACE and ACE2 Activities Reflect Intestinal Shedding and Microbiota Modulation of Renin-Angiotensin System.Biology · 2026Article
- Vascular Immune Crosstalk in COVID-19: RAAS Biomarker Signature Linking Angiotensin II to Respiratory Compromise and Soluble ACE2 to IL-13 and FGF, Revealing Therapeutic Targets.International journal of molecular sciences · 2026Article
- A synthetic angiotensin II/ACE2-based hormone shunt controlling experimental hypertension.Nature communications · 2026Article
- Neuroinflammation and Oxidative Stress in Parkinson's Disease, Alzheimer's Disease, and COVID-19: Microglia-Neutrophil Interaction.ACS omega · 2026Review
- The Post-COVID syndrome caused by excessive inflammation: pathogenesis, potential targets and therapeutic agents.Frontiers in pharmacology · 2026Review
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- A model including CD15, ACE2 and age efficiently predicts COVID-19 severity.Scientific reports · 2025Article
- Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.Disease models & mechanisms · 2025Review
- Impact of Obesity and Ageing on the Expression of Key Mediators of SARS-CoV-2 Infection in Human Adipose Tissue.International journal of molecular sciences · 2025Article
- Assessment of Selected Biochemical Parameters of the Renin-Angiotensin-Aldosterone System in Repeat Convalescent Plasma Donors in the Context of Long-Term Changes Following SARS-CoV-2 Infection.Journal of clinical medicine · 2025Article
- Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives.Molecular and cellular biochemistry · 2025Review
- Vasoactive Intestinal Peptide (VIP) in COVID-19 Therapy-Shedding of ACE2 and TMPRSS2 via ADAM10.International journal of molecular sciences · 2025Article
- DNA Salivary Methylation Levels of the ACE2 Promoter Are Not Related to ACE2 (International journal of molecular sciences · 2025Article
126 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Coronavirus Disease 2019 (COVID-19) has already caused hundreds of thousands of deaths worldwide in a few months. Cardiovascular disease, hypertension, diabetes and chronic lung disease have been identified as the main COVID-19 comorbidities. Moreover, despite similar infection rates between men and women, the most severe course of the disease is higher in elderly and co-morbid male patients. Therefore, the occurrence of specific comorbidities associated with renin-angiotensin system (RAS) imbalance mediated by the interaction between angiotensin-converting enzyme 2 (ACE2) and desintegrin and metalloproteinase domain 17 (ADAM17), along with specific genetic factors mainly associated with type II transmembrane serine protease (TMPRSS2) expression, could be decisive for the clinical outcome of COVID-19. Indeed, the exacerbated ADAM17-mediated ACE2, TNF-α, and IL-6R secretion emerges as a possible underlying mechanism for the acute inflammatory immune response and the activation of the coagulation cascade. Therefore, in this review, we focus on the main pathophysiological aspects of ACE2, ADAM17, and TMPRSS2 host proteins in COVID-19. Additionally, we discuss a possible mechanism to explain the deleterious effect of ADAM17 and TMPRSS2 over-activation in the COVID-19 outcome.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.