Real-World Effectiveness of a Third Dose of mRNA-1273 versus BNT162b2 on Inpatient and Medically Attended COVID-19 among Immunocompromised Adults in the United States (preprint)

Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically-attended COVID-19 with 2 doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically-attended COVID-19 among IC adults in the US. The HealthVerity (HV) medical and pharmacy claims database, which contains data from >330 million patients, was the data source. Both subgroup and sensitivity analyses were conducted in addition to the core comparisons noted. In propensity score-adjusted analyses, receiving mRNA-1273 vs BNT162b2 as third dose was associated with 32% (relative risk [RR] 0.68; 95% confidence interval [CI] 0.51-0.89) , 29% (0.71; 0.57-0.86), and 23% (0.77; 0.62-0.93) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically-attended COVID-19 were 8% (0.92; 0.86-0.98), 6% (0.94; 0.90-0.98), and 2% (0.98; 0.94-1.02), respectively. Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically-attended COVID-19 among IC adults in the US.

Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages (preprint)

Background: Emerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. Methods: In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases during 9/1/2022-6/30/2023 were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to [≥]2 or 0 doses of original monovalent vaccine, respectively. Outcomes were BA.4/BA.5- or XBB-related infection, emergency department/urgent care (ED/UC) encounters, and hospitalization. Results: The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14-60 days and 121-180 days was 52.7% (46.9-57.8%) and 35.5% (-2.8%-59.5%) for infection, and 59.3% (49.7-67.0%) and 33.2% (-28.2-68.0%) for ED/UC encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9-85.1%) and 52.0% (-1.2-77.3%) at 14-60 days and 61-120 days, respectively. rVE against XBB at 14-60 days and 121-180 days, was 48.8% (33.4-60.7%) and -3.9% (-18.1-11.3%) for infection, 70.7% (52.4-82.0%) and 15.7% (-6.0-33.2%) for ED/UC encounters, and 87.9% (43.8-97.4%) and 57.1% (17.0-77.8%) for hospitalization. Results for VE and subgroup analyses (age, immunocompromise, and previous SARS-CoV-2 infection) were similar to rVE analyses. Conclusions: rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic adjustment of vaccines to target emerging variants and revaccination may be important in reducing COVID-19 morbidity and mortality.