Sex differences in susceptibility, severity, and outcomes of coronavirus disease 2019: Cross-sectional analysis from a diverse US metropolitan area

Vahidy, Farhaan S; Pan, Alan; Ahnstedt, Hilda; Munshi, Yashasvee; Choi, H. Alex; Tiruneh, Yordanos M.; Nasir, Khurram; Kash, Bita A.; Andrieni, Julia; McCullough, Louise D.

doi:10.1371/journal.pone.0245556

Cited by 201 publications

(188 citation statements)

References 18 publications

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“…The presence of multiple comorbidities has been associated with a worse prognosis and higher mortality rate since the start of the COVID-19 pandemic [28]. As also reported by the most recent publications [17,29], we con rmed that cardiovascular diseases and endocrinopathies, especially diabetes mellitus, are the most frequent comorbidities in patients admitted to our hospital, even though with no sex differences. This is in contrast with some recently published data obtained in 340 Italian and Spanish patients in whom cardiovascular disorders were more frequent in males [18].…”

Section: Discussionsupporting

confidence: 82%

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: 82%

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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“…Previous studies showed that AKI was more common in male patients compared to females (Su et al, 2020;Vahidy et al, 2021). However, our study found that the incidence of AKI was higher in females than males.…”

Section: Discussioncontrasting

confidence: 77%

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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“…These data contrast with the presence of severe infection in 80% of Conv and higher frequency of males. The observed sex distribution is consistent with previous findings suggesting females exhibit robust T-cell responses and are less prone to severe SARS-CoV-2 infection and death than males (Takahashi et al, 2020;Jin et al, 2020;Vahidy et al, 2021). No significant differences in age distribution between NSC and Conv were found excluding age as one of the factors accounting for the differences in disease severity observed.…”

Section: Discussionsupporting

confidence: 91%

Highly functional Cellular Immunity in SARS-CoV-2 Non-Seroconvertors is associated with immune protection

Kilpeläinen

Jiménez-Moyano

Blanch-Lombarte

et al. 2021

Preprint

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The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (NSC) recovered from infection. We performed an immune comparative analysis of SARS-CoV-2 infected individuals stratified by the absence or presence of seroconversion and disease severity. We report high levels of total naïve and low effector CD8+ T cells in NSC. Moreover, polyfunctional Nucleocapsid (NP)-specific CD8+ T-cell responses, as well as reduced levels of T-cell activation monitored by PD-1 and activation-induced markers, were distinctive immunological traits in NSC. Longitudinal data support the stability of the NSC phenotype over three months. Our results implicate highly functional SARS-CoV-2 Spike and NP T-cell responses with low immune activation in protection from disease severity in the absence of seroconversion.SUMMARYTo understand SARS-CoV-2 specific T-cell immunity in the absence of seroconversion, we characterized immunological features of Non-Seroconvertors recovered from infection. Highly functional specific T-cell responses and low immune activation were determinants of immune protection from severe disease.

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Sex differences in susceptibility, severity, and outcomes of coronavirus disease 2019: Cross-sectional analysis from a diverse US metropolitan area

Cited by 201 publications

References 18 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

Highly functional Cellular Immunity in SARS-CoV-2 Non-Seroconvertors is associated with immune protection

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