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1.
Vaccines (Basel) ; 10(6)2022 May 26.
Article in English | MEDLINE | ID: covidwho-1869857

ABSTRACT

Assessing COVID-19 vaccine effectiveness against emerging SARS-CoV-2 variants is crucial for determining future vaccination strategies and other public health strategies. When clinical effectiveness data are unavailable, a common method of assessing vaccine performance is to utilize neutralization assays using post-vaccination sera. Neutralization studies are typically performed across a wide array of settings, populations and vaccination strategies, and using different methodologies. For any comparison and meta-analysis to be meaningful, the design and methodology of the studies used must at minimum address aspects that confer a certain degree of reliability and comparability. We identified and characterized three important categories in which studies differ (cohort details, assay details and data reporting details) and that can affect the overall reliability and/or usefulness of neutralization assay results. We define reliability as a measure of methodological accuracy, proper study setting concerning subjects, samples and viruses, and reporting quality. Each category comprises a set of several relevant key parameters. To each parameter, we assigned a possible impact (ranging from low to high) on overall study reliability depending on its potential to influence the results. We then developed a reliability assessment tool that assesses the aggregate reliability of a study across all parameters. The reliability assessment tool provides explicit selection criteria for inclusion of comparable studies in meta-analyses of neutralization activity of SARS-CoV-2 variants in post-vaccination sera and can also both guide the design of future neutralization studies and serve as a checklist for including important details on key parameters in publications.

2.
Clin Infect Dis ; 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1860834

ABSTRACT

BACKGROUND: Male sex and old age are risk factors for severe COVID-19, but the intersection of sex and aging on antibody responses to SARS-CoV-2 vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (75-98 years) before and after three doses of SARS-CoV-2 mRNA vaccination, and from younger adults (18-74 years) post-dose two, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S-receptor binding domain [S-RBD], and nucleocapsid [N]), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOC). RESULTS: Vaccination induced greater antibody titers in older females than males, with both age and frailty associated with reduced antibody responses in males, but not females. Responses declined significantly in the six months following the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with disparities being greater in males than females. CONCLUSION: Older and frail males may be more vulnerable to breakthrough infections due to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330314

ABSTRACT

Background Male sex and old age are risk factors for severe COVID-19, but the intersection of sex and aging on antibody responses to SARS-CoV-2 vaccines has not been characterized. Methods Plasma samples were collected from older adults (75-98 years) before and after three doses of SARS-CoV-2 mRNA vaccination, and from younger adults (18-74 years) post-dose two, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S-receptor binding domain [S-RBD], and nucleocapsid [N]) and functional activity against S were measured against the vaccine virus and variants of concern (VOC). Results Vaccination induced greater antibody titers in older females than males, with both age and frailty associated with reduced antibody responses to vaccine antigens in males, but not females. ACE2 binding inhibition declined more than anti-S or anti-S-RBD IgG in the six months following the second dose (28-fold vs. 12- and 11-fold decreases in titer). The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOC were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOC than females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with disparities being greater in males than females. Conclusion Older and frail males may be more vulnerable to breakthrough infections due to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population. Brief summary SARS-CoV-2 mRNA vaccination induces greater antibody response in older females than males, and age and frailty reduce responses in males only. These effects are eliminated by a third vaccine dose, highlighting the need for third dose coverage, especially in older males.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320952

ABSTRACT

BACKGROUND Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. We sought to characterize sex differences in hormone levels and cytokine responses in critically ill COVID-19 patients. METHODS We performed a retrospective cohort study of critically ill COVID-19 patients. Males and females were compared. Multivariate regression was performed to assess the association between sex hormones, cytokine responses and the requirement for extracorporeal membrane oxygenation (ECMO) treatment. RESULTS We analyzed sex hormone levels (estradiol and testosterone) of n =181 male and female individuals. These consisted of n =50 critically ill COVID-19 patients ( n =39 males, n =11 females), n =42 critically ill non-COVID-19 patients ( n =27 males, n =15 females), n =39 non-COVID-19 patients with coronary heart diseases (CHD) ( n =25 males, n =14 females) and n =50 healthy individuals ( n =30 males, n =20 females). We detected highest estradiol levels in critically ill male COVID-19 patients compared to non-COVID-19 patients ( p =0.0123), patients with CHD ( p =0.0002) or healthy individuals ( p =0.0007). Lowest testosterone levels were detected in critically ill male COVID-19 patients compared to non-COVID-19 patients ( p =0.0094), patients with CHD ( p =0.0068) or healthy individuals ( p <0.0001). No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends in estradiol levels were observed. In critically ill male COVID-19 patients, cytokine and chemokine responses (IFN-γ, p =0.0301;IL-1RA, p =0.0160;IL-6, p =0.0145;MCP-1, p =0.0052;MIP-1α, p =0.0134) were significantly elevated in those with higher Sequential Organ Failure Assessment (SOFA) scores (8-11). Linear regression analysis revealed that herein IFN-γ levels correlate with estradiol levels in male and female COVID-19 patients (R 2 =0.216, =0.0009). Male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment in the course of their ICU stay ( p =0.0009). CONCLUSIONS We identified high estradiol and low testosterone levels as a hallmark of critically ill male COVID-19 patients. Elevated estradiol levels in critically ill male COVID-19 patients were positively associated with IFN-γ levels and increased risk for ECMO requirement.

5.
Front Immunol ; 12: 720952, 2021.
Article in English | MEDLINE | ID: covidwho-1417084

ABSTRACT

The ongoing COVID-19 pandemic has increased awareness about sex-specific differences in immunity and outcomes following SARS-CoV-2 infection. Strong evidence of a male bias in COVID-19 disease severity is hypothesized to be mediated by sex differential immune responses against SARS-CoV-2. This hypothesis is based on data from other viral infections, including influenza viruses, HIV, hepatitis viruses, and others that have demonstrated sex-specific immunity to viral infections. Although males are more susceptible to most viral infections, females possess immunological features that render them more vulnerable to distinct immune-related disease outcomes. Both sex chromosome complement and related genes as well as sex steroids play important roles in mediating the development of sex differences in immunity to viral infections.


Subject(s)
COVID-19/pathology , Severity of Illness Index , Sex Characteristics , CD4 Lymphocyte Count , CD4-CD8 Ratio , Cytokines/blood , Female , Humans , Immunity, Innate/genetics , Immunity, Innate/immunology , Male , SARS-CoV-2/immunology , Sex Factors
6.
Emerg Microbes Infect ; 10(1): 1807-1818, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1360311

ABSTRACT

Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. In this study, we analysed sex hormone levels (estradiol and testosterone) of male and female COVID-19 patients (n = 50) admitted to an intensive care unit (ICU) in comparison to control non-COVID-19 patients at the ICU (n = 42), non-COVID-19 patients with the most prevalent comorbidity (coronary heart diseases) present within the COVID-19 cohort (n = 39) and healthy individuals (n = 50). We detected significantly elevated estradiol levels in critically ill male COVID-19 patients compared to all control cohorts. Testosterone levels were significantly reduced in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Linear regression analysis revealed that among a broad range of cytokines and chemokines analysed, IFN-γ levels are positively associated with estradiol levels in male and female COVID-19 patients. Furthermore, male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment. Thus, we herein identified that disturbance of sex hormone metabolism might present a hallmark in critically ill male COVID-19 patients.


Subject(s)
COVID-19/mortality , COVID-19/pathology , Estradiol/blood , Testosterone/blood , Aged , Aged, 80 and over , COVID-19/blood , Critical Care , Critical Illness , Extracorporeal Membrane Oxygenation , Female , Humans , Hypogonadism/pathology , Intensive Care Units , Interferon-gamma/blood , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Distribution
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