17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection

Breithaupt‐Faloppa, Ana Cristina; Correia, Cristiano de Jesus; Prado, Carla M.; Stilhano, Roberta Sessa; Ureshino, Rodrigo Portes; Moreira, Luíz Felipe Pinho

doi:10.6061/clinics/2020/e1980

Cited by 66 publications

(70 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A relative protection of females over males has also been observed in other studies with experimental animal models of acute lung injury [ 22 ]; intriguingly, this protection was lost in ovariectomized mice, but restored upon estrogen replacement [ 23 ]. The 17β-estradiol molecule attenuates lung vascular permeability and edema [ 24 ], and estrogens reduce the pulmonary vasoconstriction during hypoxia by increasing levels of prostacyclin and nitric oxide (NO) [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Seeland

Coluzzi

Simmaco

et al. 2020

BMC Med

109

105

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Seeland

Coluzzi

Simmaco

et al. 2020

BMC Med

109

105

View full text Add to dashboard Cite

show abstract

“…Reports also suggest that the expression of human ACE2, which is the receptor for SARS-CoV-2, is regulated by Estrogen [ 44 ]. Therefore, Estradiol agonist may have a protective role against COVID-19 [ 45 ]. Recently, Estrogen patch is under clinical trial to evaluate its efficacy against COVID-19 (NCT04359329).…”

Section: Discussionmentioning

confidence: 99%

Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19

Barh

Tiwari

Weener³

et al. 2020

Computers in Biology and Medicine

View full text Add to dashboard Cite

SARS-CoV-2 has ushered a global pandemic with no effective drug being available at present. Although several FDA-approved drugs are currently under clinical trials for drug repositioning, there is an on-going global effort for new drug identification. In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. We found that: (i) Interactome-based infection pathways differ from the other three omics-based profiles. (ii) Viral process, mRNA splicing, cytokine and interferon signaling, and ubiquitin mediated proteolysis are important pathways in SARS-CoV-2 infection. (iii) SARS-CoV-2 infection also shares pathways with Influenza A, Epstein-Barr virus, HTLV-I, Measles, and Hepatitis virus. (iv) Further, bacterial, parasitic, and protozoan infection pathways such as Tuberculosis, Malaria, and Leishmaniasis are also shared by this virus. (v) A total of 50 candidate drugs, including the prophylaxis agents and pathway specific inhibitors are identified against COVID-19. (vi) Betamethasone, Estrogen, Simvastatin, Hydrocortisone, Tositumomab, Cyclosporin A etc. are among the important drugs. (vii) Ozone, Nitric oxide, plasma components, and photosensitizer drugs are also identified as possible therapeutic candidates. (viii) Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc may be the candidate prophylaxis agents. Nearly 70% of our identified agents are previously suggested to have anti-COVID-19 effects or under clinical trials. Among our identified drugs, the ones that are not yet tested, need validation with caution while an appropriate drug combination from these candidate drugs along with a SARS-CoV-2 specific antiviral agent is needed for effective COVID-19 management.

show abstract

“…Estrogens have demonstrated beneficial actions against viral infections and respiratory complications, as clinically observed by better outcomes in women during reproductive age [159,[247][248][249][250][251][252][253][254][255][256][257][258][259], due to their protective effect on endothelial function, vasodilation in the pulmonary vasculature, stimulation stimulate of the humoral response to viral infections [159,[247][248][249][250][251][252][253], and modulation of inflammatory responses [248,249], leading to improved outcomes in acute lung injuries of any etiology [254][255][256][257][258][259]. Estrogens favorably modulates the RAAS in females [260][261][262], whereas the androgenmediated TMPRSS2 expression has dual correlation with estrogens [248,263,264].…”

Section: Of Minor Relevancementioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

View full text Add to dashboard Cite

Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

show abstract

17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection

Cited by 66 publications

References 128 publications

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19

Repurposing existing drugs for COVID-19: an endocrinology perspective

Contact Info

Product

Resources

About