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Recently, Balcázar-Hernández et al. [1] published the findings of an interesting study that aimed at evaluating the clinical features, severity, and mortality related to COVID-19 among hospitalized mid-aged and older women. Risk factors related to the disease severity and mortality of these women were also analyzed. The study had a retrospective design in hospitalized female patients with COVID-19 attended between March and July 2020 at three medical institutions of Mexico: General Hospital of Mexico ‘Eduardo Liceaga’, Regional Hospital of High Specialty Ixtapaluca, and General Hospital of Cuautitlán. The clinical features, severity, and mortality of women aged 45 years and older were compared to those of younger women aged <45 years. Severity was assessed by the requirement for invasive mechanical ventilation (IMV). During the study period of a total of 480 hospitalized COVID-19 patients, 31.6% (n=152) were women (n=48 younger and n=104 older ones). The authors found that men presented a lower rate of hypertension yet greater disease severity when compared to women. Mean age of the older women was 50.5 years, with one third presenting diabetes or hypertension, and 76.7% were overweight or obese. Overall, mortality rate was 38.4% and a quarter required IMV. Older women presented a higher frequency of hypertension, IMV requirement, and mortality. Age 45 or more (odds ratio 2.7; 95% confidence interval 1.21-6.27; p=0.01) and IMV requirement (odds ratio 3.0; 95% confidence interval 1.34-6.76; p=0.004) predicted mortality. The authors conclude that severity and mortality are increased in mid-aged and older women with COVID-19 when compared to younger ones.


To date, the SARS-CoV-2 has infected millions of individuals worldwide causing high mortality rates and severe physical sequelae. The pandemic has also had a negative impact on society, economy, health care, lifestyle and personal relationships. Basal health status, sex, age, lifestyle, immune status, and current co-morbidities may determine the evolution of the infection and related complications [2]. Importantly, gender differences related to the outcomes of COVID-19 have been noted, with a higher rate of adverse outcomes and deaths observed in men as compared to women [3]. In this sense, the biological, immunological, and endocrinological differences between women and men have been proposed as influencing factors for COVID-19 outcomes [3]. In addition, older patients with COVID-19 are more likely to progress to severe disease, with a higher chance of mortality. Despite these findings, as the authors mention there is a little information about COVID-19 outcomes in women, especially in mid-aged and older ones. The present study showed that this COVID-19 female population had greater disease severity and higher mortality when compared to younger ones. This suggests female age as an important determinant of severity and mortality independent of comorbidities. There was a higher rate of hypertension in the older female population; however, it was not a risk factor for mortality in the present series. As authors mention there is a need for larger studies, due to the fact that diabetes, obesity, and hypertension are important risk factors [4], and should be considered in mid-aged and older women due to high prevalence of these conditions in this age group. In addition to age, hypoestrogenism needs also to be evaluated as a contributing aspect, since it is associated to an increase in metabolic risk in the Mexican population [5]. Estrogens and progesterone have anti-inflammatory actions on innate immunity, including the promotion of anti-inflammatory cytokine profile and suppression of pro-inflammatory cytokine production [6].

The study has limitations (retrospective design and small sample size); however, findings are interesting and put into perspective female age as a determinate of disease severity and related mortality. A potential strength of the study is being performed in a clinical setting among an understudied COVID-19 population. Despite the mentioned limitations, the authors conclude that severity and mortality are increased in mid-aged and older women with COVID-19 compared to younger ones. There is a need for more information regarding COVID-19 outcomes in relation to gender and age in order to perform clinical care and treatment approach in a personalized manner. Mid-aged and older women deserve special attention: the early diagnosis and treatment of COVID-19 is essential to improve prognosis.

Peter Chedraui, MD, PhD
Instituto de Investigación e Innovación en Salud Integral
Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador


  1. Balcázar-Hernández L, Martínez-Murillo C, Ramos-Peñafiel C, Pellón Tellez K, Li B, Manuel-Apolinar L, Basurto L. Women and COVID-19: severity and mortality in hospitalized middle-aged and older patients. Climacteric. 2021;24(3):313-315.
  2. Chedraui P, Pérez-López FR. The severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) infection and the climacteric woman. Climacteric. 2020;23(6):525-527.
  3. Pérez-López FR, Tajada M, Savirón-Cornudella R, Sánchez-Prieto M, Chedraui P, Terán E. Coronavirus disease 2019 and gender-related mortality in European countries: A meta-analysis. Maturitas. 2020;141:59-62.
  4. Zhou Y, Yang Q, Chi J, Dong B, Lv W, Shen L, Wang Y. Comorbidities and the risk of severe or fatal outcomes associated with coronavirus disease 2019: A systematic review and meta-analysis. Int J Infect Dis. 2020;99:47-56.
  5. Fernández Muñoz MJ, Basurto Acevedo L, Córdova Pérez N, et al. Epicardial adipose tissue is associated with visceral fat, metabolic syndrome, and insulin resistance in menopausal women. Rev Esp Cardiol (Engl Ed). 2014;67(6):436-41.
  6. Mauvais-Jarvis F, Klein SL, Levin ER. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology. 2020;161(9):bqaa127.

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