Biological sex impacts COVID-19 outcomes

Sabra L Klein, Santosh Dhakal, Rebecca L Ursin, Sharvari Deshpande, Kathryn Sandberg, Franck Mauvais-Jarvis, Sabra L Klein, Santosh Dhakal, Rebecca L Ursin, Sharvari Deshpande, Kathryn Sandberg, Franck Mauvais-Jarvis

Abstract

The current novel coronavirus disease 2019 (COVID-19) pandemic is revealing profound differences between men and women in disease outcomes worldwide. In the United States, there has been inconsistent reporting and analyses of male-female differences in COVID-19 cases, hospitalizations, and deaths. We seek to raise awareness about the male-biased severe outcomes from COVID-19, highlighting the mechanistic differences including in the expression and activity of angiotensin-converting enzyme 2 (ACE2) as well as in antiviral immunity. We also highlight how sex differences in comorbidities, which can be associated with both age and race, impact male-biased outcomes from COVID-19.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Sex-disaggregated numbers of COVID-19 cases,…
Fig 1. Sex-disaggregated numbers of COVID-19 cases, hospitalizations, and deaths per 100,000 people in NYC.
Data were accessed from https://www1.nyc.gov/site/doh/covid/covid-19-data.page on April 11, 2020. COVID-19, novel coronavirus disease 2019; NYC, New York City.

References

    1. Klein SL, Pekosz A, Passaretti C, Anker M, Olukoya P: Sex, gender and influenza In. Geneva: World Health Organization; 2010: 1–58.
    1. Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL: Impact of sex and gender on COVID-19 outcomes in Europe. Biology of Sex Differences 11(1):29 10.1186/s13293-020-00304-9
    1. Sex, gender and COVID-19. [cited 2020 Apr 11].
    1. McMichael TM, Currie DW, Clark S, Pogosjans S, Kay M, Schwartz NG, Lewis J, Baer A, Kawakami V, Lukoff MD et al.: Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington. New England Journal of Medicine March 27, 2020. 10.1056/NEJMoa2005412 2020
    1. Wenham C, Smith J, Morgan R, Gender, Group C-W: COVID-19: the gendered impacts of the outbreak. Lancet 2020.
    1. South AM, Diz D, Chappell MC: COVID-19, ACE2 and the Cardiovascular Consequences. Am J Physiol Heart Circ Physiol 2020.
    1. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC et al.: Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426(6965):450–454. 10.1038/nature02145
    1. Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, Mazet JK, Hu B, Zhang W, Peng C et al.: Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 2013, 503(7477):535–538. 10.1038/nature12711
    1. Chen Y, Guo Y, Pan Y, Zhao ZJ: Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun 2020.
    1. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R et al.: A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res 2000, 87(5):E1–9. 10.1161/01.res.87.5.e1
    1. Liu J, Ji H, Zheng W, Wu X, Zhu JJ, Arnold AP, Sandberg K: Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17beta-oestradiol-dependent and sex chromosome-independent. Biology of sex differences 2010, 1(1):6 10.1186/2042-6410-1-6
    1. Arnold AP, Cassis LA, Eghbali M, Reue K, Sandberg K: Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases. Arterioscler Thromb Vasc Biol 2017, 37(5):746–756. 10.1161/ATVBAHA.116.307301
    1. Klein SL, Flanagan KL: Sex differences in immune responses. Nat Rev Immunol 2016, 16(10):626–638. 10.1038/nri.2016.90
    1. vom Steeg LG, Klein SL: SeXX Matters in Infectious Disease Pathogenesis. PLoS Pathog 2016, 12(2):e1005374 10.1371/journal.ppat.1005374
    1. Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S: Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection. J Immunol 2017, 198(10):4046–4053. 10.4049/jimmunol.1601896
    1. Vermillion MS, Ursin RL, Kuok DIT, Vom Steeg LG, Wohlgemuth N, Hall OJ, Fink AL, Sasse E, Nelson A, Ndeh R et al.: Production of amphiregulin and recovery from influenza is greater in males than females. Biol Sex Differ 2018, 9(1):24 10.1186/s13293-018-0184-8
    1. Meng Y, Wu P, Lu W, Liu K, Ma K, Huang L, Cai J, Zhang H, Qin Y, Sun H et al.: Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: a retrospective study of 168 severe patients. PLoS Pathog 2020, 10.1371/journal.ppat.1008520
    1. Bloch EM, Shoham S, Casadevall A, Sachais BS, Shaz B, Winters JL, van Buskirk C, Grossman BJ, Joyner M, Henderson JP et al.: Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest 2020.
    1. Zeng F, Dai C, Cai P, Wang J, Xu L, Li J, Hu G, Wang L: A comparison study of SARS-CoV-2 IgG antibody between male and female COVID-19 patients: a possible reason underlying different outcome between gender. medRxiv preprint 2020.
    1. Karlberg J, Chong DS, Lai WY: Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am J Epidemiol 2004, 159(3):229–231. 10.1093/aje/kwh056
    1. Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, Liu L, Shan H, Lei C-l, Hui DSC et al.: Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine February 28, 2020. 10.1056/NEJMoa2002032 2020
    1. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, Greninger AL, Pipavath S, Wurfel MM, Evans L et al.: Covid-19 in Critically Ill Patients in the Seattle Region—Case Series. New England Journal of Medicine 2020.
    1. Onder G, Rezza G, Brusaferro S: Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. Jama 2020.
    1. New York State Department of Health COVID 19 Tracker. [cited 2020 Apr 11] .
    1. Louisiana Department of Health Coronavirus (COVID-19). [cited 2020 Apr 11].
    1. Mauvais-Jarvis F, Bairey Merz CN, Barnes PJ, Brinton RD, Carrero J-J, DeMeo DL, de Vries GJ, Epperson CN, Govindan R, Klein SL et al.: Sex and gender: Modifiers of health, disease and medicine. Lancet in press.
    1. Chen N, Zhou M, Dong XP, Qu J, Gong F, Han Y, Qui Y, Wang J, Liu Y, Wei YQ et al.: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020, 395 (10223):507–513.
    1. Yancy CW: COVID-19 and African Americans. JAMA 2020.

Source: PubMed

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