Sex Differences on Clinical Characteristics, Severity, and Mortality in Adult Patients With COVID-19: A Multicentre Retrospective Study

Sha, Jing; Qie, Guoqiang; Yao, Qingchun; Sun, Wenqing; Wang, Cuiyan; Zhang, Zhongfa; Wang, Xing‐Guang; Wang, Peng; Jiang, Jinjiao; Bai, Xi; Chu, Yufeng; Meng, Mei

doi:10.3389/fmed.2021.607059

Cited by 47 publications

(62 citation statements)

References 43 publications

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“…This feature has been documented worldwide because a male bias in COVID-19 mortality was reported in the 37 out of the 38 countries that have provided sex disaggregated data [8]. Other studies have also reported that a higher proportion of men were hospitalized than females [17,23]. Our data showed that this is not the case for younger (< 45 years) and older patients (> 75 years), in whom the hospitalizations of females and males were similar.…”

Section: Discussionsupporting

confidence: 55%

Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves.

Quaresima

Scarpazza

Sottini

et al. 2021

Preprint

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Background: Coronavirus Disease 2019 (COVID-19) severity seems to be influenced by genetic background, sex, age, and presence of specific comorbidities. So far, little attention has been paid to sex-specific variations of demographic, clinical and laboratory features of COVID-19 patients referred to the same hospital in the two consecutive pandemic waves.Methods: Demographic, clinical and laboratory data were collected in 1,000 COVID-19 patients (367 females and 633 males), 500 hospitalized in the first wave and 500 in the second one, at the ASST Spedali Civili of Brescia from March to December 2020. Statistical analyses have been employed to compare data obtained in females and males, taking into account their age, and during the first and second COVID-19 waves. Results: The mean age at the time of hospitalization was similar in females and males but was significantly higher for both in the second wave; the time elapsed from symptoms onset to hospital admission did not differ between sexes in the two waves and no correlation was observed between delayed hospital admission and length of hospitalization. The number of multi-symptomatic males was higher than that of females and patients with a higher number of comorbidities were more frequently admitted to intensive care unit (ICU) and more frequently died. Older males remained in ICU longer than females and showed a longer disease duration, mainly the first wave. The highest levels of white blood cells, neutrophils, C-reactive protein and fibrinogen were significantly higher in males and in the first, and along with higher levels of D-dimer, ferritin, lactate dehydrogenase and procalcitonin which were preferentially documented in patients requiring ICU or died. While the ICU death rate was higher in males, the overall death rate did not differ between the sexes; however, the deceased women were older.Conclusions: These data indicate that once patients were hospitalized, the risk of dying was similar between females and males. Therefore, future studies should aim at understanding the reasons why, for a given number of SARS-CoV-2 infection, less females develop the disease requiring hospitalization.

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Section: Discussionsupporting

confidence: 55%

Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves.

Quaresima

Scarpazza

Sottini

et al. 2021

Preprint

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“…However, there was no significant difference in disease severity and mortality between postmenopausal and premenopausal females after eliminating the confounding of age in this study. A retrospective study in patients with COVID-19 in China also reported that estrogen might not be directly related to the lower mortality in females (Sha et al, 2021). Due to the small sample size after PSM, large sample investigations are still needed to verify this conclusion.…”

Section: Discussionmentioning

confidence: 99%

“…Estrogen has been reported to play a crucial role in disease outcomes in COVID-19 patients, attributed to its ability to reduce inflammatory IL-6, IL-8 and TNF-a levels (Alwani et al, 2021). However, this conclusion is not consistent (Alwani et al, 2021;Sha et al, 2021). This study aimed to provide information on differences in clinical characteristics and outcomes between male and female patients and explore the effect of estrogen on disease outcomes.…”

Section: Introductionmentioning

confidence: 98%

“…Sex- and gender- specific epidemiologic observations would help deepen our understanding towards COVID-19 and make sex- or gender- specific recommendations ( Bhopal, 2020 ; Wenham et al., 2020 ). Although current studies have reported the impact of sex on patients with COVID-19, studies based on Chinese populations are scarce and limited in small sample sizes ( Sha et al., 2021 ). Estrogen has been reported to play a crucial role in disease outcomes in COVID-19 patients, attributed to its ability to reduce inflammatory IL-6, IL-8 and TNF-α levels ( Alwani et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Sex-Disaggregated Data on Clinical Characteristics and Outcomes of Hospitalized Patients With COVID-19: A Retrospective Study

Wang

Jiang

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundSex and gender are crucial variables in coronavirus disease 2019 (COVID-19). We sought to provide information on differences in clinical characteristics and outcomes between male and female patients and to explore the effect of estrogen in disease outcomes in patients with COVID-19.MethodIn this retrospective, multi-center study, we included all confirmed cases of COVID-19 admitted to four hospitals in Hubei province, China from Dec 31, 2019 to Mar 31, 2020. Cases were confirmed by real-time RT-PCR and were analyzed for demographic, clinical, laboratory and radiographic parameters. Random-effect logistic regression analysis was used to assess the association between sex and disease outcomes.ResultsA total of 2501 hospitalized patients with COVID-19 were included in the present study. The clinical manifestations of male and female patients with COVID-19 were similar, while male patients have more comorbidities than female patients. In terms of laboratory findings, compared with female patients, male patients were more likely to have lymphopenia, thrombocytopenia, inflammatory response, hypoproteinemia, and extrapulmonary organ damage. Random-effect logistic regression analysis indicated that male patients were more likely to progress into severe type, and prone to ARDS, secondary bacterial infection, and death than females. However, there was no significant difference in disease outcomes between postmenopausal and premenopausal females after propensity score matching (PSM) by age.ConclusionsMale patients, especially those age-matched with postmenopausal females, are more likely to have poor outcomes. Sex-specific differences in clinical characteristics and outcomes do exist in patients with COVID-19, but estrogen may not be the primary cause. Further studies are needed to explore the causes of the differences in disease outcomes between the sexes.

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“…(7) A metaanalysis of 58 studies showed men with a 1.57-fold higher odds ratio for mortality and a 1.65-fold higher for severe infection than women (8). Recently Sha et al confirmed again that mortality of women is lower than in men but noticed no-difference in inhospital mortality in women < 55 years of age compared with the same age men (9). Beside several limitations of this study like retrospective, exploratory, no measurement of oestrogen level and no information of the history of hormone therapy, they opened the discussion whether an association of oestradiol and mortality in COVID-19 disease exists.…”

Section: Epidemiology-sars-cov-2 Infection and Covid-19 Mortalitymentioning

confidence: 99%

Sensitive to Infection but Strong in Defense—Female Sex and the Power of Oestradiol in the COVID-19 Pandemic

Newson¹,

Manyonda

Lewis³

et al. 2021

Front. Glob. Womens Health

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The incidence of SARS-CoV2 infections is around 15% higher in premenopausal women compared to age matched men, yet the fatality rate from COVID-19 is significantly higher in men than women for all age strata. Sex differences have also been observed in recent epidemics including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), with SARS-CoV 2 virus infection sex differences appear more dramatic. The regulation and expression of the angiotensin converting enzyme 2 (ACE2) is the key for this special coronavirus SARS-CoV-2 to enter the cell. 17β-oestradiol increases expression level and activity of angiotensin converting enzyme-2 (ACE2) and the alternative signaling pathway of Ang II via the angiotensin II receptor type II (AT2R) and the Mas receptor is more dominant in female sex than in male sex. Maybe a hint to explain the higher infection risk in women. The same hormonal milieu plays a major role in protecting women where morbidity and mortality are concerned, since the dominant female hormone, oestradiol, has immune-modulatory properties that are likely to be protective against virus infections. It is also known that the X chromosome contains the largest number of immune-related genes, potentially conferring an advantage to women in efficient immune responsiveness. Lifestyle factors are also likely to be contributory. Premenopausal women could possibly face higher exposure to infection (hence higher infection rates) because economic conditions are often less favorable for them with less opportunity for home office work because of jobs requiring mandatory attendance. Due to the additional task of childcare, it is likely that contact times with other people will be longer. Women generally make healthier lifestyle choices, thus reducing the disease burden that confers high risk of mortality in COVID-19 infected men. This narrative review aims to present key concepts and knowledge gaps on the effects of oestrogen associated with SARS-CoV2 infection and COVID-19 disease.

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Sex Differences on Clinical Characteristics, Severity, and Mortality in Adult Patients With COVID-19: A Multicentre Retrospective Study

Cited by 47 publications

References 43 publications

Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves.

Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves.

Sex-Disaggregated Data on Clinical Characteristics and Outcomes of Hospitalized Patients With COVID-19: A Retrospective Study

Sensitive to Infection but Strong in Defense—Female Sex and the Power of Oestradiol in the COVID-19 Pandemic

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