ReviewAmerican journal of physiology. Heart and circulatory physiology2021
Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones.
Review in American journal of physiology. Heart and circulatory physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
118 citing papers in PubMed, 4 syntheses or guidelines pooled it, 180 citations in OpenAlex.
- Association between COVID-19 and sexual health: an umbrella review.Annals of medicine · 2023Pooled it
- Innate immunity to SARS-CoV-2 infection: a review.Epidemiology and infection · 2022Pooled it
- Adaptive immunity to SARS-CoV-2 infection: A systematic review.Frontiers in immunology · 2022Pooled it
- COVID-19 pandemic: insights into molecular mechanisms leading to sex-based differences in patient outcomes.Expert reviews in molecular medicine · 2021Pooled it
- Trial
- The problem with one-size-fits-all medicine: Biological sex and the aging immune system.PLoS biology · 2026Article
- SARS-CoV-2 infection and its effects on toxicity and survival in non-metastatic nasopharyngeal carcinoma: a matched cohort study.BMC cancer · 2026Article
- SARS-CoV-2 infection reduces the number of spermatogonial stem cells and dysregulates the transcriptional landscape of the human testis.Research square · 2026Article
- Association of angiotensin converting enzyme type 2 serum level and gene polymorphisms with multiple sclerosis.Scientific reports · 2026Article
- Effects of heavy metal exposure on oral microbial communities in women with different menopausal status.Microbiology spectrum · 2026Article
- The Application of Single-cell RNA Sequencing Technology in the Research of Sino-Nasal Diseases.Clinical reviews in allergy & immunology · 2026Review
- Whole-Body Cryotherapy at -90 °C for 9 Weeks: Effects on Immune Function, Stress, and Immune-Related and Vascular Blood Parameters in Healthy Adults-Results of an Exploratory One-Armed Pilot Study.Journal of clinical medicine · 2026Article
- Quantitative dissection of sexual dimorphism in mice through Y-linked gene knockouts and multivariate phenotyping.Scientific reports · 2026Article
- Sex differences in response to COVID-19 infection: a retrospective study based on emergency medical team interventions.Frontiers in public health · 2026Article
- Transcriptomic profiling reveals immune signatures associated with potential COVID-19 susceptibility and a predictive framework in a Chinese cohort.Frontiers in immunology · 2026Article
- SARS-CoV-2-induced dysregulation in ADAR editing patterns persists post viral clearance in individuals with mild COVID-19.Frontiers in cellular and infection microbiology · 2026Article
- Assessing the impact of COVID-19 pandemic on all-cause mortality and child mortality in a population cohort of Iganga Mayuge HDSS in Eastern Uganda (2015-2021).Population health metrics · 2025Article
- The Role of ACE2 in SARS-CoV-2 Infection, Pathogenesis, and Antiviral Interventions.Journal of medical virology · 2025Review
- Understanding sex and gender disparities in COVID-19 mortality: a narrative review beyond biology.Biology of sex differences · 2025Review
- Profiling of proteases involved in SARS-CoV-2 pathogenesis in human saliva: Influence of age and gender.Journal, genetic engineering & biotechnology · 2025Article
58 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
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Biological sex is increasingly recognized as a critical determinant of health and disease, particularly relevant to the topical COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. Epidemiological data and observational reports from both the original SARS epidemic and the most recent COVID-19 pandemic have a common feature: males are more likely to exhibit enhanced disease severity and mortality than females. Sex differences in cardiovascular disease and COVID-19 share mechanistic foundations, namely, the involvement of both the innate immune system and the canonical renin-angiotensin system (RAS). Immunological differences suggest that females mount a rapid and aggressive innate immune response, and the attenuated antiviral response in males may confer enhanced susceptibility to severe disease. Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19, either to serve as a protective mechanism by deactivating the RAS or as the receptor for viral entry, respectively. Loss of membrane ACE2 and a corresponding increase in plasma ACE2 are associated with worsened cardiovascular disease outcomes, a mechanism attributed to a disintegrin and metalloproteinase (ADAM17). SARS-CoV-2 infection also leads to ADAM17 activation, a positive feedback cycle that exacerbates ACE2 loss. Therefore, the relationship between cardiovascular disease and COVID-19 is critically dependent on the loss of membrane ACE2 by ADAM17-mediated proteolytic cleavage. This article explores potential mechanisms involved in COVID-19 that may contribute to sex-specific susceptibility focusing on the innate immune system and the RAS, namely, genetics and sex hormones. Finally, we highlight here the added challenges of gender in the COVID-19 pandemic.
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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.