Sex- or Gender-specific Differences in the Clinical Presentation, Outcome, and Treatment of SARS-CoV-2

Wolfe, Jeannette; Safdar, Basmah; Madsen, Tracy E.; Sethuraman, Kinjal N.; Becker, Bruce M.; Greenberg, Marna Rayl; McGregor, Alyson J.

doi:10.1016/j.clinthera.2021.01.015

Cited by 17 publications

(19 citation statements)

References 79 publications

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“…Known biological differences in adaptive and innate immune responses between sexes explain some of these observed differences (4). Socio-cultural gender constructs also influence these outcomes through differing exposures to the disease (such as high occupational exposure in frontline healthcare workers, who are predominantly women), risk factors for severe disease (such as higher smoking rates in men), existence of comorbidities, and engagement with healthcare services for prevention, detection, and treatment (typically lower in men) (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Sex and Gender in COVID-19 Vaccine Research: Substantial Evidence Gaps Remain

Vassallo

Shajahan

Harris

et al. 2021

Front. Glob. Womens Health

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Since the start of the COVID-19 pandemic there has been a global call for sex/gender-disaggregated data to be made available, which has uncovered important findings about COVID-19 testing, incidence, severity, hospitalisations, and deaths. This mini review scopes the evidence base for efficacy, effectiveness, and safety of COVID-19 vaccines from both experimental and observational research, and asks whether (1) women and men were equally recruited and represented in vaccine research, (2) the outcomes of studies were presented or analysed by sex and/or gender, and (3) there is evidence of sex and/or gender differences in outcomes. Following a PubMed search, 41 articles were eligible for inclusion, including seven randomised controlled trials (RCTs), 11 cohort studies, eight cross-sectional surveys, eight routine surveillance studies, and seven case series. Overall, the RCTs contained equal representation of women and men; however, the observational studies contained a higher percentage of women. Of 10 studies with efficacy data, only three (30%) presented sex/gender-disaggregated results. Safety data was included in 35 studies and only 12 (34%) of these presented data by sex/gender. For those that did present disaggregated data, overall, the majority of participants reporting adverse events were women. There is a paucity of reporting and analysis of COVID-19 vaccine data by sex/gender. Research should be designed in a gender-sensitive way to present and, where possible analyse, data by sex/gender to ensure that there is a robust and specific evidence base of efficacy and safety data to assist in building public confidence and promote high vaccine coverage.

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Section: Introductionmentioning

confidence: 99%

Sex and Gender in COVID-19 Vaccine Research: Substantial Evidence Gaps Remain

Vassallo

Shajahan

Harris

et al. 2021

Front. Glob. Womens Health

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show abstract

“…Biomarkers and qualities (such as sex) in COVID-19 have been shown to manifest in negative disease outcomes (hospitalization, ICU, and mortality) and in differences in immune responses [ 11 ]. For example, age as an influence on comorbidities as a covariate for fatality is strongly sex specific [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, S protein has been chosen as an antigen for several approved vaccines worldwide [ 10 ]. Additionally, males have consistently shown to have higher mortality and hospitalization rates in comparison to females [ 11 ]. We are using male and female as synonymous for biological sex unless otherwise specified as gender.…”

Section: Introductionmentioning

confidence: 99%

CIDO ontology updates and secondary analysis of host responses to COVID-19 infection based on ImmPort reports and literature

et al. 2021

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Background With COVID-19 still in its pandemic stage, extensive research has generated increasing amounts of data and knowledge. As many studies are published within a short span of time, we often lose an integrative and comprehensive picture of host-coronavirus interaction (HCI) mechanisms. As of early April 2021, the ImmPort database has stored 7 studies (with 6 having details) that cover topics including molecular immune signatures, epitopes, and sex differences in terms of mortality in COVID-19 patients. The Coronavirus Infectious Disease Ontology (CIDO) represents basic HCI information. We hypothesize that the CIDO can be used as the platform to represent newly recorded information from ImmPort leading the reinforcement of CIDO. Methods The CIDO was used as the semantic platform for logically modeling and representing newly identified knowledge reported in the 6 ImmPort studies. A recursive eXtensible Ontology Development (XOD) strategy was established to support the CIDO representation and enhancement. Secondary data analysis was also performed to analyze different aspects of the HCI from these ImmPort studies and other related literature reports. Results The topics covered by the 6 ImmPort papers were identified to overlap with existing CIDO representation. SARS-CoV-2 viral S protein related HCI knowledge was emphasized for CIDO modeling, including its binding with ACE2, mutations causing different variants, and epitope homology by comparison with other coronavirus S proteins. Different types of cytokine signatures were also identified and added to CIDO. Our secondary analysis of two cohort COVID-19 studies with cytokine panel detection found that a total of 11 cytokines were up-regulated in female patients after infection and 8 cytokines in male patients. These sex-specific gene responses were newly modeled and represented in CIDO. A new DL query was generated to demonstrate the benefits of such integrative ontology representation. Furthermore, IL-10 signaling pathway was found to be statistically significant for both male patients and female patients. Conclusion Using the recursive XOD strategy, six new ImmPort COVID-19 studies were systematically reviewed, the results were modeled and represented in CIDO, leading to the enhancement of CIDO. The enhanced ontology and further seconary analysis supported more comprehensive understanding of the molecular mechanism of host responses to COVID-19 infection.

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“…The potential role for hormones in COVID-19 was also shown in an analysis of females using the COVID Symptom Tracker Application in the United Kingdom: this showed COVID-19 infections and hospitalisation were significantly lower in women aged 18–45 taking oral contraceptives compared with matched women not taking oral contraceptives [ 66 ]. Of course, there are gender-associated behaviours that may affect COVID-19 infections and mortalities, for instance males are more likely to be smokers which increases ACE2 expression [ 1 ]. Overall, there does appear to be a gender and hormone bias in the severity of COVID-19 infections.…”

Section: Gender and Covid-19mentioning

confidence: 99%

“…Rodent studies have shown that, throughout embryonic development and sexual maturation, the lung structure and functional output can be affected by ligands of the androgen receptor (AR) and glucocorticoid receptor (GR), and to a lesser extent oestrogen receptor (ER). There is increasing evidence of gender differences in terms of COVID severity and a potential role of hormones and their target nuclear receptors in mediating COVID infections [ 1 ]. Most notably, lung cell infection by the SARS-CoV-2 virus (which causes COVID-19), as well as related viruses, has been shown to be facilitated by host cell proteins regulated by steroid hormones, especially androgens.…”

Section: Introductionmentioning

confidence: 99%

Roles of steroid receptors in the lung and COVID-19

Leach

Brooke

Bevan

2021

Essays in Biochemistry

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COVID-19 symptoms and mortality are largely due to its devastating effects in the lungs. The disease is caused by the SARS (Severe Acute Respiratory Syndrome)-CoV-2 coronavirus, which requires host cell proteins such as ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) for infection of lung epithelia. The expression and function of the steroid hormone receptor family is important in many aspects that impact on COVID-19 effects in the lung – notably lung development and function, the immune system, and expression of TMPRSS2 and ACE2. This review provides a brief summary of current knowledge on the roles of the steroid hormone receptors [androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), mineralocorticoid receptor (MR) and oestrogen receptor (ER)] in the lung, their effects on host cell proteins that facilitate SARS-CoV-2 uptake, and provides a snapshot of current clinical trials investigating the use of steroid receptor (SR) ligands to treat COVID-19.

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Sex- or Gender-specific Differences in the Clinical Presentation, Outcome, and Treatment of SARS-CoV-2

Cited by 17 publications

References 79 publications

Sex and Gender in COVID-19 Vaccine Research: Substantial Evidence Gaps Remain

Sex and Gender in COVID-19 Vaccine Research: Substantial Evidence Gaps Remain

CIDO ontology updates and secondary analysis of host responses to COVID-19 infection based on ImmPort reports and literature

Roles of steroid receptors in the lung and COVID-19

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