Sex‐based differences in severity and mortality in COVID‐19

Alwani, Mustafa; Yassin, Aksam; Al‐Zoubi, Raed M.; Aboumarzouk, Omar M.; Nettleship, Joanne E.; Kelly, Daniel; Al-Qudimat, Ahmad; Shabsigh, Ridwan

doi:10.1002/rmv.2223

Cited by 91 publications

(120 citation statements)

References 115 publications

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“…Studies have indicated that psychological, physiological, and behavioral factors could play a major role in the intensity of the immune response provoked by the vaccine [ 16 , 17 , 18 ]. Studies have consistently reported higher morbidity and mortality of SARS-CoV-2 infection in women and people of older age, excluding children younger than 5 years old that are also vulnerable [ 19 , 20 , 21 ]. However, concerning the impact of age and sex on vaccine efficiency, the data so far are limited and contradictory [ 18 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers

et al. 2021

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Anti-SARS-CoV-2 spike RBD (receptor-binding domain) IgG antibody levels were monitored in 1643 volunteer healthcare workers of Eginition, Evangelismos, and Konstantopoulio General Hospitals (Athens, Greece), who underwent vaccination with two doses of COVID-19 BNT162b2 mRNA vaccine (Pfizer) and had no history of SARS-CoV-2 infection. Venous blood was collected 20–30 days after the second vaccine dose and anti-RBD IgG levels were determined using CMIA SARS-CoV-2 IgG II Quant (Abbott) on ARCHITECT i System or ADVIA Centaur SARS-CoV-2 IgG (Siemens) on Centaur XP platform. From the total population of 1643 vaccinees (533 M/1110 F; median age = 49; interquartile range-IQR = 40–56), 1636 (99.6%) had anti-SARS-CoV-2 IgG titers above the positivity threshold of the assay used. One-Way ANOVA Kruskal-Wallis H test showed a statistically significant difference in the median of antibody titers between the different age groups (p < 0.0001). Consistently, Spearman’s correlation coefficient (r) for IgGs and age as continuous variables was −0.2380 (p = 1.98 × 10−17). Moreover, antibody titers were slightly higher by 1.2-mean fold (p = 3 × 10−6) in the total female population of the three hospitals (median = 1594; IQR = 875–2584) as compared to males (median = 1292; IQR = 671.9–2188). The present study supports that BNT162b2 vaccine is particularly effective in producing high anti-SARS-CoV-2 IgG levels in healthy individuals, and this humoral response is age- and gender-dependent.

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Section: Introductionmentioning

confidence: 99%

Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers

et al. 2021

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“…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 ). However, this conclusion is not consistent ( Alwani et al., 2021 ; Sha et al., 2021 ).…”

Section: Introductionmentioning

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-α 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: 99%

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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“…Toll-like receptors (TLRs) that recognize bacterial or viral DNA/RNA are the key innate immune pattern recognition receptors ( Alwani et al, 2021 ). They are expressed on both the innate immunity cells (DCs, macrophages, natural killer cells) and adaptive immunity cells (T cells and B cells) ( Khanmohammadi and Rezaei, 2021 ).…”

Section: Mechanisms Of Sex Differences In Covid-19 Pathogenesismentioning

confidence: 99%

Sex-related susceptibility in coronavirus disease 2019 (COVID-19): Proposed mechanisms

Aksoyalp

Samur

2021

European Journal of Pharmacology

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The importance of sex differences is increasingly acknowledged in the incidence and treatment of disease. Accumulating clinical evidence demonstrates that sex differences are noticeable in COVID-19, and the prevalence, severity, and mortality rate of COVID-19 are higher among males than females. Sex-related genetic and hormonal factors and immunological responses may underlie the sex bias in COVID-19 patients. Angiotensin-converting enzyme 2 ( ACE2 ) and transmembrane protease/serine subfamily member 2 ( TMPRSS2 ) are essential proteins involved in the cell entry of SARS-CoV-2. Since ACE2 is encoded on the X-chromosome, a double copy of ACE2 in females may compensate for virus-mediated downregulation of ACE2 , and thus ACE2 -mediated cellular protection is greater in females. The X chromosome also contains the largest immune-related genes leading females to develop more robust immune responses than males. Toll-like receptor-7 (TLR-7), one of the key players in innate immunity, is linked to sex differences in autoimmunity and vaccine efficacy, and its expression is greater in females. Sex steroids also affect immune cell function. Estrogen contributes to higher CD4 + and CD8 + T cell activation levels, and females have more B cells than males. Sex differences not only affect the severity and progression of the disease, but also alter the efficacy of pharmacological treatment and adverse events related to the drugs/vaccines used against COVID-19. Administration of different drugs/vaccines in different doses or intervals may be useful to eliminate sex differences in efficacy and side/adverse effects. It should be noted that studies should include sex-specific analyses to develop further sex-specific treatments for COVID-19.

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Sex‐based differences in severity and mortality in COVID‐19

Cited by 91 publications

References 115 publications

Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers

Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers

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

Sex-related susceptibility in coronavirus disease 2019 (COVID-19): Proposed mechanisms

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