COVID-19 vaccine trials and sex-disaggregated data.
Ontology highlight
ABSTRACT:
SUBMITTER: Hussain M
PROVIDER: S-EPMC8726001 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundSex and gender are believed to influence vaccine response. Yet, the relationship between sex and gender and COVID-19 vaccine efficacy is poorly understood and remains under-investigated.MethodsWe conducted a systematic review to determine whether and to what extent post-approval COVID-19 vaccine effectiveness (VE) studies report sex-disaggregated VE data. We searched four publication and pre-publication databases and additional grey literature sources for relevant published/preprint studies released between 1 January 2020 and 1 October 2021 (i.e., pre-Omicron era). We included observational studies providing VE estimates for one or more licensed/approved COVID-19 vaccines and including both males and females. Two reviewers independently assessed study eligibility, extracted data, and assessed risk-of-bias through a modified version of Cochrane's ROBINS-I tool. A qualitative data synthesis was performed.ResultsHere we show that, among 240 eligible publications, 68 (28.3%) do not report the sex distribution among participants. Only 21/240 (8.8%) studies provide sex-disaggregated VE estimates, and high between-study heterogeneity regarding design, target population, outcomes, and vaccine type/timing prevent the assessment of sex in determining COVID-19 VE across studies.ConclusionsOur findings indicate that few COVID-19 vaccine research publications account for sex. Improved adherence to recommended reporting guidelines will ensure that the evidence generated can be used to better understand the relationship between sex and gender and VE.
| S-EPMC10196298 | biostudies-literature
Project description: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.
| S-EPMC8187910 | biostudies-literature
Project description:COVID-19 has joined the long list of sexually dimorphic human disorders. Higher lethality in men, evident in the first reports from China, was confirmed in the subsequent Italian outbreak. Newspapers and scientific journals commented on this finding and the preexisting conditions, biological processes, and behavioral differences that may underlie it. However, little appeared to be released about sex differences in severity of disease, comorbidities, rate of recovery, length of hospital stay, or number of tests performed. Systematic analysis of official websites for 20 countries and 6 US states revealed a wide disparity in sex-disaggregated data made available to the public and scholars. Only a handful reported cases by sex. None of the other characteristics, including deaths, were stratified by sex at the time. Beyond suboptimal sex disaggregation, we found a paucity of usable raw data sets and a generalized lack of standardization of captured data, making comparisons difficult. A second round of data capture in April found more complete, but even more disparate, information. Our analysis revealed a wide range of sex ratios among confirmed cases. In countries where a male bias was initially reported, the proportion of women dramatically increased in 3 weeks. Analysis also revealed a complex pattern of sex ratio variation with age. Accurate, peer-reviewed, analysis of harmonized, sex-disaggregated data for characteristics of epidemics, such as availability of testing, suspected source of infection, or comorbidities, will be critical to understand where the observed disparities come from and to generate evidence-based recommendations for decision-making by governments.
| S-EPMC7781558 | biostudies-literature
Project description:To speed the development of vaccines against SARS-CoV-2, the United States Federal Government has funded multiple phase 3 trials of candidate vaccines. A single 11-member data and safety monitoring board (DSMB) monitors all government-funded trials to ensure coordinated oversight, promote harmonized designs, and allow shared insights related to safety across trials. DSMB reviews encompass 3 domains: (1) the conduct of trials, including overall and subgroup accrual and data quality and completeness; (2) safety, including individual events of concern and comparisons by randomized group; and (3) interim analyses of efficacy when event-driven milestones are met. Challenges have included the scale and pace of the trials, the frequency of safety events related to the combined enrollment of over 100 000 participants, many of whom are older adults or have comorbid conditions that place them at independent risk of serious health events, and the politicized environment in which the trials have taken place.
| S-EPMC8240876 | biostudies-literature
Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
2022-10-14 | PXD031969 | Pride
Project description:Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines ("Pfizer" vaccine dose 1 and 2, "Moderna" vaccine dose 1 and 2, and "Janssen" vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports between December 14, 2020 and September 17, 2021. AE rankings of the five vaccine groups calculated separately by RCT and VAERS were consistent, especially for systemic AEs. For severe AEs reported in VAERS, the reported risks of thrombosis and GBS after Janssen vaccine were highest. The reported risk of shingles after the first dose of Moderna vaccine was highest, followed by the second dose of the Moderna vaccine. The reported risk of myocarditis was higher after the second dose of Pfizer and Moderna vaccines. The reported risk of anaphylaxis was higher after the first dose of Pfizer vaccine. Limitations of this study are the inherent biases of the spontaneous reporting system data, and only including three pivotal RCTs and no comparison with other active vaccine safety surveillance systems.
| S-EPMC9243073 | biostudies-literature
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
| S-SCDT-EMM-2021-15227 | biostudies-other
Project description:Blood collected from adults pre vaccination and post vaccination to study the immune effects of COVID-19 vaccination and how they relate to antibody and T-cell responses.
2023-01-12 | GSE199750 | GEO
Project description:While rapid development and roll out of COVID-19 vaccines is necessary in a pandemic, the process limits the ability of clinical trials to assess longer-term vaccine efficacy. We leveraged COVID-19 surveillance data in the U.S. to evaluate vaccine efficacy in U.S. Government-funded COVID-19 vaccine efficacy trials with a three-step estimation process. First, we used a compartmental epidemiological model informed by county-level surveillance data, a "population model", to estimate SARS-CoV-2 incidence among the unvaccinated. Second, a "cohort model" was used to adjust the population SARS-CoV-2 incidence to the vaccine trial cohort, taking into account individual participant characteristics and the difference between SARS-CoV-2 infection and COVID-19 disease. Third, we fit a regression model estimating the offset between the cohort-model-based COVID-19 incidence in the unvaccinated with the placebo-group COVID-19 incidence in the trial during blinded follow-up. Counterfactual placebo COVID-19 incidence was estimated during open-label follow-up by adjusting the cohort-model-based incidence rate by the estimated offset. Vaccine efficacy during open-label follow-up was estimated by contrasting the vaccine group COVID-19 incidence with the counterfactual placebo COVID-19 incidence. We documented good performance of the methodology in a simulation study. We also applied the methodology to estimate vaccine efficacy for the two-dose AZD1222 COVID-19 vaccine using data from the phase 3 U.S. trial (ClinicalTrials.gov # NCT04516746). We estimated AZD1222 vaccine efficacy of 59.1% (95% uncertainty interval (UI): 40.4%-74.3%) in April, 2021 (mean 106 days post-second dose), which reduced to 35.7% (95% UI: 15.0%-51.7%) in July, 2021 (mean 198 days post-second-dose). We developed and evaluated a methodology for estimating longer-term vaccine efficacy. This methodology could be applied to estimating counterfactual placebo incidence for future placebo-controlled vaccine efficacy trials of emerging pathogens with early termination of blinded follow-up, to active-controlled or uncontrolled COVID-19 vaccine efficacy trials, and to other clinical endpoints influenced by vaccination.
| S-EPMC11257040 | biostudies-literature
Project description:BackgroundMany studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses.MethodsWe systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated.Findings30 studies were eligible for inclusion, investigating remdesivir (n = 2), lopinavir/ritonavir (n = 5), favipiravir (n = 1), umifenovir (n = 1), hydroxychloroquine/chloroquine (n = 8), convalescent plasma (n = 6), interleukin-6 (IL-6) pathway inhibitors (n = 5), interleukin-1 (IL-1) pathway inhibitors (n = 1) and corticosteroids (n = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females.InterpretationAnalyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care.FundingNone.
| S-EPMC7701906 | biostudies-literature