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Re: “Sex and Gender-Related Differences in COVID-19 Diagnoses and SARS-CoV-2 Testing Practices During the First Wave of the Pandemic: The Dutch Lifelines COVID-19 Cohort Study” by Ballering et al.

2022; Mary Ann Liebert, Inc.; Volume: 31; Issue: 6 Linguagem: Inglês

10.1089/jwh.2022.0015

1931-843X

Marco Rossato, Angelo Di Vincenzo, Alessandra Andrisani, Loris Marin, Federico Capone, Roberto Vettor,

COVID-19 Clinical Research Studies

Journal of Women's HealthVol. 31, No. 6 Letters to the EditorsFree AccessRe: “Sex and Gender-Related Differences in COVID-19 Diagnoses and SARS-CoV-2 Testing Practices During the First Wave of the Pandemic: The Dutch Lifelines COVID-19 Cohort Study” by Ballering et al.Marco Rossato, Angelo Di Vincenzo, Alessandra Andrisani, Loris Marin, Federico Capone, and Roberto VettorMarco RossatoAddress correspondence to: Marco Rossato, MD, PhD, Clinica Medica 3, Department of Medicine—DIMED, University Hospital of Padova, Via Giustiniani 2, Padova 35128, Italy E-mail Address: marco.rossato@unipd.itClinica Medica 3, Department of Medicine—DIMED, University Hospital of Padova, Padova, Italy.Search for more papers by this author, Angelo Di Vincenzohttps://orcid.org/0000-0002-7678-5671Clinica Medica 3, Department of Medicine—DIMED, University Hospital of Padova, Padova, Italy.Search for more papers by this author, Alessandra AndrisaniUnit of Gynecology and Obstetrics, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy.Search for more papers by this author, Loris MarinUnit of Gynecology and Obstetrics, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy.Search for more papers by this author, Federico CaponeClinica Medica 3, Department of Medicine—DIMED, University Hospital of Padova, Padova, Italy.Search for more papers by this author, and Roberto VettorClinica Medica 3, Department of Medicine—DIMED, University Hospital of Padova, Padova, Italy.Search for more papers by this authorPublished Online:14 Jun 2022https://doi.org/10.1089/jwh.2022.0015AboutSectionsView articleSupplemental MaterialPDF/EPUBView Supplemental Data Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleDear Editor:We have read with interest the article by Ballering et al. on gender-related differences in coronavirus disease 2019 (COVID-19) patients.1 Although they did not observe any gender difference in COVID-19 diagnosis, the epidemiological studies on COVID-19 have showed an unambiguous gender difference regarding hospitalization and severe clinical evolution, with men more susceptible than women.2 The majority of the studies considered male and female COVID-19 patients without differentiating for age ranges. Furthermore, it is still unclear if these differences are due to a lower SARS-CoV-2 infection rate of women or because women are “protected” from severe forms of COVID-19.We analyzed the report of the Italian National Institute of Health on 1-year total number of SARS-CoV-2 confirmed positive cases (from late February 2020 to January 27, 2021),3 considering age, sex, and deaths with reference to SARS-CoV-2 infection and lethality index using the chi-square test and the odds ratio (OR) (Supplementary Table S1).The analysis of the number of SARS-CoV-2 positive women was higher than that of men [1,284,531 (51.7%) vs. 1,202,371 (48.3%), respectively, p < 0.0001].3 On the contrary males showed a fatality rate significantly higher than that of females (OR 1.38, confidence interval [95% CI] 1.36–1.40, p < 0.0001), except for age range 0–29 years.3 In particular, if we consider the age range 20–49 (a premenopausal age range), SARS-CoV-2 positive females are higher than men [514,633 (51.6%) vs. 483,388 (48.4%), respectively, p < 0.0001], but the fatality rate in men was 2.2 times higher than that of women (OR 2.21, 95% CI 1.93–2.54, p < 0.0001).3 In contrast, if we consider SARS-CoV-2 positive subjects >60 years (a postmenopausal age), the number of SARS-CoV-2 positive females was significantly higher than that of males [391,839 (53.2%) vs. 344,037 (46.8%), respectively, p < 0.001], but the fatality rate in men was “only” 1.43 times higher than in women (OR 1.43, 95% CI 1.41–1.45, p < 0.0001).3Our analysis of SARS-CoV-2 confirmed positive subjects in Italy indicates that women make up more of the cases of SARS-CoV-2 infection, but men appear to have more COVID-19-related severe complications leading to death. The lower fatality rate in women could be due to still unknown gender-related biological factors and to the comorbidities associated with COVID-19 negative outcomes, which are less prevalent in women than in men, particularly in women before menopause. The expression of the protein angiotensin converting enzyme 2 (ACE2), functioning as the receptor for the SARS-CoV-2 “spike” protein docking on target cells surface is stimulated by androgens and reduced by estrogens.4 Furthermore, there are gender differences in immune response to viral infections.5 Interestingly, a recent study reported that the fatality rate for COVID-19 in women >50 years taking estradiol therapy was reduced by >50% with respect to women not taking the hormone.6The detailed analysis of future data will help us to understand the role of gender and of sex hormones in the pathogenesis of COVID-19 complications, and contribute to our knowledge on this still largely unknown disease.Supplementary MaterialSupplementary Table S1References1. Ballering AV, Oertelt-Prigione S, Olde Hartman TC, et al. Sex and gender-related differences in COVID-19 diagnoses and SARS-CoV-2 testing practices during the first wave of the pandemic: The dutch lifelines COVID-19 cohort study. J Women's Health (Larchmt) 2021;30:1686–1692. Link, Google Scholar2. Pijls BG, Jolani S, Atherley A, et al. Demographic risk factors for COVID-19 infection, severity, ICU admission and death: A meta-analysis of 59 studies. BMJ Open 2021;11:e044640. Crossref, Medline, Google Scholar3. Italian Institute of Health. Available at: https://www.epicentro.iss.it/coronavirus/sars-cov-2-sorveglianza-dati Accessed January 30, 2021. Google Scholar4. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271–280.e8. Crossref, Medline, Google Scholar5. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016;16:626–638. Crossref, Medline, Google Scholar6. Seeland U, Coluzzi F, Simmaco M, et al. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. BMC Med 2020;18:369. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited byResponse to Rossato et al. Aranka Viviënne Ballering, Sabine Oertelt-Prigione, Tim C. Olde Hartman, and Judith G.M. Rosmalen14 June 2022 | Journal of Women's Health, Vol. 31, No. 6 Volume 31Issue 6Jun 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Marco Rossato, Angelo Di Vincenzo, Alessandra Andrisani, Loris Marin, Federico Capone, and Roberto Vettor.Re: “Sex and Gender-Related Differences in COVID-19 Diagnoses and SARS-CoV-2 Testing Practices During the First Wave of the Pandemic: The Dutch Lifelines COVID-19 Cohort Study” by Ballering et al..Journal of Women's Health.Jun 2022.895-896.http://doi.org/10.1089/jwh.2022.0015Published in Volume: 31 Issue 6: June 14, 2022Online Ahead of Print:May 31, 2022PDF download