The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6–16.4%) and 5.1% (95% CI: 3.2–6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5–20.8%) and 10.7% (8.2–13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults.

This study aimed to evaluate the vaccine effectiveness (VE) of mRNA-1273.815, a 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine, at preventing COVID-19-related hospitalizations and any medically attended COVID-19 in adults. In a linked EHR-claims dataset, we identified US adults (≥18 years) who received the mRNA-1273.815 vaccine (exposed cohort) between September 12 and December 15, 2023, matched 1:1 to individuals who did not receive a 2023-2024 updated COVID-19 vaccine (unexposed cohort). Cohorts were balanced using inverse probability of treatment weighting on demographics, vaccination and infection history, and underlying medical conditions. Study cohorts were followed until December 31, 2023 for COVID-19-related hospitalizations and medically attended COVID-19. Cox regression was used to estimate hazard ratios (HR) and VE. Subgroup analyses were performed for adults ≥50, adults ≥65, and individuals with underlying medical conditions. Overall, 859,335 matched pairs of mRNA-1273.815 recipients and unexposed adults were identified. The mean (SD) age was 63 (16) years. More than 60% of individuals in both cohorts had an underlying medical condition. Among the overall adult population, VE was 60.2% (95% CI: 53.4-66.0%) against COVID-19-related hospitalization and 33.1% (30.2%-35.9%) against medically attended COVID-19 over a median follow-up of 63 (IQR: 44-78) days. VE estimates by age and underlying medical conditions were similar. These results demonstrate the significant protection provided by mRNA-1273.815 against COVID-19-related hospitalizations and any medically attended COVID-19 in adults, regardless of vaccination history, and support CDC recommendations to stay up-to-date with COVID-19 vaccination to prevent COVID-19-related outcomes, including hospitalizations.

Influenza and COVID-19 contribute significantly to the infectious disease burden during the respiratory season, but their relative burden remains unknown. This study characterizes the frequency and severity of medically attended COVID-19 and influenza during the peak of the 2022–2023 influenza season in the pediatric, adult, and older adult populations and characterizes the prevalence of underlying conditions among patients hospitalized with COVID-19. This cross-sectional analysis included individuals in the Veradigm EHR Database linked to Komodo claims data with a medical encounter between 1 October 2022 and 31 March 2023 (study period). Patients with medical encounters were identified with a diagnosis of COVID-19 or influenza during the study period and stratified based on the highest level of care received with that diagnosis. Among 23,526,196 individuals, there were more COVID-19-related medical encounters than influenza-related encounters, overall and by outcome. Hospitalizations with COVID-19 were more common than hospitalizations with influenza overall (incidence ratio = 4.6) and in all age groups. Nearly all adults hospitalized with COVID-19 had at least one underlying medical condition, but 37.1% of 0–5-year-olds and 25.0% of 6–17-year-olds had no underlying medical conditions. COVID-19 was associated greater burden than influenza during the peak of the 2022–2023 influenza season.

Background/Objectives: This retrospective cohort study evaluated the relative vaccine effectiveness (rVE) of two bivalent (original/Omicron BA.4/BA.5) vaccines mRNA-1273.222 versus the BNT162b2 Bivalent in preventing COVID-19-related outcomes in adults with underlying medical conditions associated with increased risk for severe COVID-19. Methods: In a linked electronic health record/claims dataset, US adults (≥18 years) with ≥1 underlying medical condition of interest who received either the bivalent vaccine between 31 August 2022 and 28 February 2023 were identified. The inverse probability of treatment weighting was used to adjust for cohort differences. Cohorts were followed up for COVID-19-related hospitalizations and outpatient encounters until 31 May 2023. Hazard ratios and rVEs were estimated using Cox regression. Subgroup analyses were performed on individuals with pre-specified comorbid conditions. Results: 757,572 mRNA-1273.222 and 1,204,975 BNT162b2 Bivalent recipients were identified. The adjusted rVE over a median follow-up of 198 days was 10.9% (6.2%–15.2%) against COVID-19-related hospitalization and 3.2% (1.7%–4.7%) against COVID-19-related outpatient encounters. rVE estimates for COVID-19 hospitalizations among subgroups with comorbid conditions were as follows: diabetes 15.1% (8.7%–21.0%), cerebro- and cardiovascular disease 14.7% (9.0%–20.1%), chronic lung disease 11.9% (5.1%–18.2%), immunocompromised 15.0% (7.2%–22.2%), chronic kidney disease 8.4% (0.5%–15.7%). Conclusions: Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations.

Introduction In the post-pandemic era, people with underlying medical conditions continue to be at increased risk for severe COVID-19 disease, yet COVID-19 vaccination uptake remains low. This study estimated the clinical and economic impact of updated 2023/24 Moderna COVID-19 vaccination among high-risk adults versus no 2023/24 vaccination and versus updated Pfizer/BioNTech vaccination. Methods A static Markov model was adapted for high-risk adults, including immunocompromised (IC), chronic lung disease (CLD), chronic kidney disease (CKD), cardiovascular disease (CVD), and diabetes mellitus (DM) populations in the United States (US). Results Vaccination with the updated Moderna vaccine at current coverage rates was estimated to prevent considerable COVID-19 hospitalizations in CLD (101,309), DM (97,358), CVD (47,830), IC (14,834), and CKD (13,558) populations versus no 2023/24 vaccination. Vaccination also provided net medical cost-savings of US$399 million (M)–2129M (healthcare payer) and $457M–2531M (societal perspective), depending on population. The return-on-investment was positive across all conditions ($1.10–$2.60 gain for every $1 invested). Healthcare savings increased with a relative 10% increase in current vaccination coverage ($439M–$2342M), and from meeting US 2030 targets of 70% coverage ($1096M–$5707M). Based on higher vaccine effectiveness observed in real-world evidence studies, updated Moderna vaccination was estimated to prevent additional COVID-19 hospitalizations in DM (13,105), CLD (10,359), CVD (6241), IC (1979), and CKD (942) versus Pfizer/BioNTech’s updated vaccine, with healthcare payer and societal cost-savings, making it the dominant strategy. Healthcare savings per patient vaccinated with Moderna versus Pfizer/BioNTech’s updated vaccine were $31.00–$59.00, depending on population. Results were robust across sensitivity/scenario analyses. Conclusions Updated 2023/24 Moderna COVID-19 vaccination was estimated to provide significant health benefits through prevention of COVID-19 in high-risk populations, and cost-savings to healthcare payers and society, versus no 2023/24 vaccination and updated Pfizer/BioNTech vaccination. Increasing current low COVID-19 vaccination coverage rates was estimated to be cost-saving while preventing many more severe infections and hospitalizations in these high-risk populations. A graphical abstract is available with this article. Graphical Abstract