Evidence for treatment with estradiol for women with SARS-CoV-2 infection
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Abstract
Background
Given that an individual’s age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options?
Methods
An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15–49 years) and peri-/post-menopausal (> 50 years).
Results
The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is higher in women than men (by about + 15%) and, in contrast, the fatality rate is higher in men (about + 50%). Interestingly, the relationships between these quantities are linked to age: pre-adolescent girls and boys had the same risk of infection and fatality rate, while adult premenopausal women had a significantly higher risk of infection than men in the same 5-year age stratum (about 16,000 vs. 12,000 cases). This ratio changed again in peri- and postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years, there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17ß-estradiol influences expression of the human angiotensin-converting enzyme 2 (ACE2) protein, which plays a role in SARS-CoV-2 cellular entry, propensity score matching was performed for the women’s sub-cohort, comparing users vs. non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women > 50 years receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95% CI [0.18, 0.62] and the hazard ratio (HR) was 0.29, 95% CI [0.11,0.76]. For younger, pre-menopausal women (15–49 years), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels.
Conclusions
As of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone.
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SciScore for 10.1101/2020.08.21.20179671: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Prospective, placebo-controlled, randomized, double-blinded multicenter clinical trials are the gold standard of evidence generation in medicine; however, such efforts are often slow and expensive. Blinding not detected. Power Analysis not detected. Sex as a biological variable Objectives of this Study: As is known from the literature, endogenous estradiol has beneficial cardiovascular and immune system-stabilizing effects in premenopausal women, as well as within pregnancy(Dubey & Jackson, 2001; Straub, 2007). Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. …
SciScore for 10.1101/2020.08.21.20179671: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Prospective, placebo-controlled, randomized, double-blinded multicenter clinical trials are the gold standard of evidence generation in medicine; however, such efforts are often slow and expensive. Blinding not detected. Power Analysis not detected. Sex as a biological variable Objectives of this Study: As is known from the literature, endogenous estradiol has beneficial cardiovascular and immune system-stabilizing effects in premenopausal women, as well as within pregnancy(Dubey & Jackson, 2001; Straub, 2007). Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04359329 Recruiting Estrogen Patch for COVID-19 Symptoms Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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