As of February 2022, mRNA-based vaccine Comirnaty, developed by Pfizer/Biontech, was the leading COVID-19 vaccine by efficacy rate, showing around 95 percent of efficacy against COVID-19. This statistic illustrates the comparison of select COVID-19 vaccines worldwide, by efficacy.

This publication corresponds to the Common Data Model (CDM) specification of the Baseline Use Case proposed in T.5.2 (WP5) in the BY-COVID project on “SARS-CoV-2 Vaccine(s) effectiveness in preventing SARS-CoV-2 infection.” Research Question: “How effective have the SARS-CoV-2 vaccination programmes been in preventing SARS-CoV-2 infections?” Intervention (exposure): COVID-19 vaccine(s) Outcome: SARS-CoV-2 infection Subgroup analysis: Vaccination schedule (type of vaccine) Study Design: An observational retrospective longitudinal study to assess the effectiveness of the SARS-CoV-2 vaccine in preventing SARS-CoV-2 infections using routinely collected social, health and care data from several countries. A causal model was established using Directed Acyclic Graphs (DAGs) to map domain knowledge, theories and assumptions about the causal relationship between exposure and outcome. The DAG developed for the research question of interest is shown below. Cohort definition: All people eligible to be vaccinated (from 5 to 115 years old, included) or with, at least, one dose of a SARS-CoV-2 vaccine (any of the available brands) having or not a previous SARS-CoV-2 infection. Inclusion criteria: All people vaccinated with at least one dose of the COVID-19 vaccine (any available brands) in an area of residence. Any person eligible to be vaccinated (from 5 to 115 years old, included) with a positive diagnosis (irrespective of the type of test) for SARS-CoV-2 infection (COVID-19) during the period of study. Exclusion criteria: People not eligible for the vaccine (from 0 to 4 years old, included) Study period: From the date of the first documented SARS-CoV-2 infection in each country to the most recent date in which data is available at the time of analysis. Roughly from 01-03-2020 to 30-06-2022, depending on the country. Files included in this publication: Causal model (responding to the research question) SARS-CoV-2 vaccine effectiveness causal model v.1.0.0 (HTML) - Interactive report showcasing the structural causal model (DAG) to answer the research question SARS-CoV-2 vaccine effectiveness causal model v.1.0.0 (QMD) - Quarto RMarkdown script to produce the structural causal model Common data model specification (following the causal model) SARS-CoV-2 vaccine effectiveness data model specification (XLXS) - Human-readable version (Excel) SARS-CoV-2 vaccine effectiveness data model specification dataspice (HTML) - Human-readable version (interactive report) SARS-CoV-2 vaccine effectiveness data model specification dataspice (JSON) - Machine-readable version Synthetic dataset (complying with the common data model specifications) SARS-CoV-2 vaccine effectiveness synthetic dataset (CSV) [UTF-8, pipe | separated, N~650,000 registries] SARS-CoV-2 vaccine effectiveness synthetic dataset EDA (HTML) - Interactive report of the exploratory data analysis (EDA) of the synthetic dataset SARS-CoV-2 vaccine effectiveness synthetic dataset EDA (JSON) - Machine-readable version of the exploratory data analysis (EDA) of the synthetic dataset SARS-CoV-2 vaccine effectiveness synthetic dataset generation script (IPYNB) - Jupyter notebook with Python scripting and commenting to generate the synthetic dataset #### Baseline Use Case: SARS-CoV-2 vaccine effectiveness assessment - Common Data Model Specification v.1.1.0 change log #### Updated Causal model to eliminate the consideration of 'vaccination_schedule_cd' as a mediator Adjusted the study period to be consistent with the Study Protocol Updated 'sex_cd' as a required variable Added 'chronic_liver_disease_bl' as a comorbidity at the individual level Updated 'socecon_lvl_cd' at the area level as a recommended variable Added crosswalks for the definition of 'chronic_liver_disease_bl' in a separate sheet Updated the 'vaccination_schedule_cd' reference to the 'Vaccine' node in the updated DAG Updated the description of the 'confirmed_case_dt' and 'previous_infection_dt' variables to clarify the definition and the need for a single registry per person The scripts (software) accompanying the data model specification are offered "as-is" without warranty and disclaiming liability for damages resulting from using it. The software is released under the CC-BY-4.0 licence, which permits you to use the content for almost any purpose (but does not grant you any trademark permissions), so long as you note the license and give credit.

IntroductionVaccination against COVID-19 has been pivotal in reducing the global burden of the disease. However, Phase III trial results and observational studies underscore differences in efficacy across vaccine technologies and dosing regimens. Notably, mRNA vaccines have exhibited superior effectiveness compared to Adenovirus (AdV) vaccines, especially with extended dosing intervals. MethodsUsing in-host mechanistic modelling, this study elucidates these variations and unravels the biological mechanisms shaping the immune responses at the cellular level. We used data on the change in memory B cells, plasmablasts, and antibody titres after the second dose of a COVID-19 vaccine for Australian healthcare workers. Alongside this dataset, we constructed a kinetic model of humoral immunity which jointly captured the dynamics of multiple immune markers, and integrated hierarchical effects into this kinetics model, including age, dosing schedule, and vaccine type.ResultsOur analysis estimated that mRNA vaccines induced 2.1 times higher memory B cell proliferation than AdV vaccines after adjusting for age, interval between doses and priming dose. Additionally, extending the duration between the second vaccine dose and priming dose beyond 28 days boosted neutralising antibody production per plasmablast concentration by 30%. We also found that antibody responses after the second dose were more persistent when mRNA vaccines were used over AdV vaccines and for longer dosing regimens. DiscussionReconstructing in-host kinetics in response to vaccination could help optimise vaccine dosing regimens, improve vaccine efficacy in different population groups, and inform the design of future vaccines for enhanced protection against emerging pathogens.

Background: In the United States, patients with limited English proficiency face significant barriers to comprehending and acting upon health-related information, particularly during the COVID-19 pandemic. The ability of health professionals to communicate COVID-19-related information to Mandarin-speaking patients has proved critical in discussions about vaccine efficacy, side effects, and post-vaccine protection.

Methods: The authors created a one-hour educational module to help Mandarin-speaking medical students better convey COVID-19 vaccine information to Mandarin-only speakers. The module is composed of an educational guide, which introduced key terminology and addressed commonly asked questions, and pre- and post-surveys. The authors recruited 59 Mandarin-speaking medical students from 31 U.S. academic medical centers, all of whom had previously completed a medical Mandarin elective. The module and surveys were distributed and completed in August 2021. Data analysis measured the change in aggregate mean for subjective five-point Likert-scale questions and change in percent accuracy for objective knowledge-based questions.

Results: The educational module significantly improved participants' subjective comfort level in discussing the COVID-19 vaccine in English and Mandarin. The largest improvement in both English and Mandarin was demonstrated in the participant's ability to explain differences between the COVID-19 vaccines, with an aggregate mean improvement of 0.39 for English and 1.48 for Mandarin. Survey respondents also demonstrated increased percent accuracy in knowledge-based objective questions in Mandarin.

Conclusions: This module provides Mandarin-learning medical students with skills to deliver reliable information to the general population and acts as a model for the continued development of educational modules for multilingual medical professionals.

IntroductionThe emergence of SARS-CoV-2 variants of concern (VOCs), particularly Omicron, has challenged the efficacy of initial COVID-19 vaccination strategies. Booster immunizations, especially with mRNA vaccines, were introduced to enhance and prolong immune protection. However, the underlying mechanisms of humoral and cellular immunity induced by homologous versus heterologous vaccination regimens remain incompletely understood. This study aimed to elucidate the immune responses, including B cell, plasmacytoid dendritic cell (pDC), and T cell activation, following mRNA booster vaccination.MethodsIn a longitudinal cohort study, 136 individuals received three different vaccination regimens: homologous mRNA, heterologous vector-mRNA-mRNA, or heterologous vector-vector-mRNA vaccinations. Serum and peripheral blood mononuclear cells (PBMCs) were collected at multiple time points up to 64 weeks after initial vaccination. Anti-SARS-CoV-2 IgG titers and neutralization capacity against the wildtype virus and Omicron variant were measured using ELISA and cPass assays. Cellular immunity was assessed by IFN-γ release assays, and flow cytometry was employed to analyze B cell and pDC frequencies, viability, and activation markers. Functional pDC-mediated T cell activation was evaluated in mixed lymphocyte cultures.ResultsmRNA booster vaccination stabilized high anti-SARS-CoV-2 IgG titers and neutralizing activity against wildtype virus across all regimens, with the homologous mRNA group showing the highest antibody titers and Omicron neutralization capacity. Peripheral B cell frequencies and activation markers (MHC class I/II, CD86) were significantly upregulated post-booster. pDCs demonstrated enhanced antigen-presenting capacity and significantly promoted SARS-CoV-2-specific T cell IFN-γ responses in vitro. Despite differences in humoral responses between regimens, breakthrough infection rates up to 25 weeks post-booster were comparable across cohorts, suggesting compensatory mechanisms via cellular immunity.DiscussionOur findings highlight the pivotal role of pDCs and T cells in sustaining effective immunity following mRNA booster vaccination. While homologous mRNA regimens induce superior humoral responses, robust cellular immunity in heterologous regimens may balance protection levels against breakthrough infections. The study underscores the importance of integrated humoral and cellular immune responses, suggesting potential for optimized booster strategies and pDC-targeted vaccine designs to enhance long-term protection against SARS-CoV-2 and emerging variants.

BackgroundThe unrelenting emergence of SARS-CoV-2 variants has significantly challenged the efficacy of existing COVID-19 vaccines. Enhancing the stability and immunogenicity of the spike protein is critical for improving vaccine performance and addressing variant-driven immune evasion.MethodsWe developed an mRNA-based vaccine, RV-1730, encoding the Delta variant spike protein with the S6P mutation to enhance stability and immunogenicity. The vaccine’s immunogenicity and protective efficacy were evaluated in preclinical models, including monovalent (RV-1730) and bivalent (RV-1731) formulations targeting the Delta and BA.1 variants. Additionally, the effectiveness of RV-1730 as a heterologous booster following primary vaccination with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna-NIAID) was assessed.ResultsRV-1730 elicited significantly stronger B and T cell responses and more durable neutralizing antibodies compared to S2P-based vaccines. The bivalent RV-1731 vaccine demonstrated broad neutralizing activity against emerging variants, including XBB1.5 and JN.1. Importantly, RV-1730, when used as a heterologous booster following initial immunization with BNT162b2 or mRNA-1273, significantly enhanced neutralizing antibody titers against multiple variants, including Delta and Omicron. Both RV-1730 and RV-1731 provided superior protection in preclinical models, indicating enhanced efficacy due to the S6P mutation.ConclusionThe incorporation of the S6P mutation into the Delta variant spike protein significantly enhances the immunogenicity and efficacy of mRNA-based COVID-19 vaccines. The strong performance of RV-1730 as a heterologous booster and the broad-spectrum activity of the bivalent RV-1731 vaccine underscore their potential as versatile and effective vaccination strategies against SARS-CoV-2 and its evolving variants.

Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after COVID-19 infections. They also have different immune responses after doses of COVID-19 vaccination, but limited evidence is available to reveal the effectiveness and help to guide immunization programs for this subpopulation; MEDLINE, Embase, Web of Science, Cochrane Library databases, and clinicaltrials.gov were used to search literature. The pooled seroconversion rate was calculated using a random-effects model and reported with a 95% confidence interval (CI); The review includes 66 studies containing serological responses after COVID-19 vaccination in 13,050 solid cancer patients and 8550 healthy controls. The pooled seropositive rates after the first dose in patients with solid cancer and healthy controls are 55.2% (95% CI 45.9%–64.5% N = 18) and 90.2% (95% CI 80.9%–96.6% N = 13), respectively. The seropositive rates after the second dose in patients with solid cancer and healthy controls are 87.6% (95% CI 84.1%–90.7% N = 50) and 98.9% (95% CI 97.6%-99.7% N = 35), respectively. The seropositive rates after the third dose in patients with solid cancer and healthy controls are 91.4% (95% CI 85.4%–95.9% N = 21) and 99.8% (95% CI 98.1%-100.0% N = 4), respectively. Subgroup analysis finds that study sample size, timing of antibody testing, and vaccine type have influence on the results; Seroconversion rates after COVID-19 vaccination are significantly lower in patients with solid malignancies, especially after the first dose, then shrinking gradually after the following two vaccinations, indicating that subsequent doses or a booster dose should be considered for the effectiveness of this subpopulation.