ABSTRACT
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.
Subject(s)
COVID-19ABSTRACT
The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received [≥]2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%-75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable [≥]3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%-58.8%) and 82.7% (63.7%-91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.
Subject(s)
Severe Acute Respiratory Syndrome , Death , COVID-19ABSTRACT
Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against Omicron BA.4/BA.5 compared with earlier Omicron subvariants. We conducted a test-negative case-control study evaluating mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron subvariants. The study included 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged [≥]18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection was high and waned slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection was initially moderate to high (61.0%-90.6% 14-30 days post third dose) and waned rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranged between 64.3%-75.7%, and was low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 was 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 was 88.5%. Evaluation of the updated bivalent booster is warranted.
Subject(s)
COVID-19ABSTRACT
Background The recently emerged SARS-CoV-2 omicron variant raised concerns around potential escape from vaccine-elicited immunity. Limited data are available on real-world vaccine effectiveness (VE) of mRNA-1273 against omicron. Here, we report VE of 2 or 3 mRNA-1273 doses against infection and hospitalization with omicron and delta, including among immunocompromised individuals. Methods This test negative study was conducted at Kaiser Permanente Southern California. Cases were individuals aged [≥]18 years testing positive by RT-PCR with specimens collected between 12/6/2021 and 12/23/2021 with variant determined by spike gene status. Randomly sampled test negative controls were 5:1 matched to cases by age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression models were used to evaluate adjusted odds ratio (aOR) of vaccination with mRNA-1273 doses between cases and controls. VE(%) was calculated as (1-aOR)x100. Results 6657 test positive cases (44% delta, 56% omicron) were included. The 2-dose VE against omicron infection was 30.4% (95% CI, 5.0%-49.0%) at 14-90 days after vaccination and declined quickly thereafter. The 3-dose VE was 95.2% (93.4%-96.4%) against delta infection and 62.5% (56.2%-67.9%) against omicron infection. The 3-dose VE against omicron infection was low among immunocompromised individuals (11.5%; 0.0%-66.5%). None of the cases (delta or omicron) vaccinated with 3 doses were hospitalized compared to 53 delta and 2 omicron unvaccinated cases. Conclusions VE of 3 mRNA-1273 doses against infection with delta was high and durable, but VE against omicron infection was lower. VE against omicron infection was particularly low among immunocompromised individuals. No 3-dose recipients were hospitalized for COVID-19.
Subject(s)
Hepatitis D , COVID-19ABSTRACT
Background: We conducted a prospective cohort study at Kaiser Permanente Southern California to study the vaccine effectiveness (VE) of mRNA-1273 over time and during the emergence of the Delta variant. Methods: The cohort for this planned interim analysis consisted of individuals aged [≥]18 years receiving 2 doses of mRNA-1273 through June 2021, matched 1:1 to randomly selected unvaccinated individuals by age, sex, and race/ethnicity, with follow-up through September 2021. Outcomes were SARS-CoV-2 infection, and COVID-19 hospitalization and hospital death. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) comparing outcomes in the vaccinated and unvaccinated groups. Adjusted VE (%) was calculated as (1-aHR)x100. HRs and VEs were also estimated for SARS-CoV-2 infection by age, sex, race/ethnicity, and during the Delta period (June-September 2021). VE against SARS-CoV-2 infection and COVID-19 hospitalization was estimated at 0-<2, 2-<4, 4-<6, and 6-<8 months post-vaccination. Results: 927,004 recipients of 2 doses of mRNA-1273 were matched to 927,004 unvaccinated individuals. VE (95% CI) was 82.8% (82.2-83.3%) against SARS-CoV-2 infection, 96.1% (95.5-96.6%) against COVID-19 hospitalization, and 97.2% (94.8-98.4%) against COVID-19 hospital death. VE against SARS-CoV-2 infection was similar by age, sex, and race/ethnicity, and was 86.5% (84.8-88.0%) during the Delta period. VE against SARS-CoV-2 infection decreased from 88.0% at 0-<2 months to 75.5% at 6-<8 months. Conclusions: These interim results provide continued evidence for protection of 2 doses of mRNA-1273 against SARS-CoV-2 infection over 8 months post-vaccination and during the Delta period, and against COVID-19 hospitalization and hospital death.
Subject(s)
COVID-19ABSTRACT
BackgroundVaccines may elicit long-term boosting of innate immune responses that can help protect against COVID-19. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and COVID-19 outcomes at Kaiser Permanente Southern California. MethodsIn a cohort design, adults aged [≥]50 years who received [≥]1 RZV dose prior to 3/1/2020 were matched 1:2 to unvaccinated individuals and followed until 12/31/2020. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive SARS-CoV-2 test and controls had only negative tests, from 3/1/2020-12/31/2020. Adjusted odds ratios (aOR) and 95% CIs for prior receipt of RZV were estimated using logistic regression. ResultsIn the cohort design, 149,244 RZV recipients were matched to 298,488 unvaccinated individuals. The aHRs (95% CI) for COVID-19 diagnosis and hospitalization were 0.84 (0.81-0.87) and 0.68 (0.64-0.74), respectively. In the test-negative design, 8.4% of 75,726 test-positive cases and 13.1% of 340,898 test-negative controls had received [≥]1 RZV dose. The aOR (95% CI) was 0.84 (0.81-0.86). ConclusionRZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization, suggesting RZV elicits heterologous protection, possibly through trained immunity.
Subject(s)
COVID-19ABSTRACT
BackgroundReal-world studies have found high vaccine effectiveness (VE) of mRNA-based COVID-19 vaccines, but reduced VE against the Delta variant and waning protection have been reported, with few studies examining mRNA-1273 variant-specific VE. MethodsWe conducted a test-negative case-control study at Kaiser Permanente Southern California. Whole genome sequencing was conducted for SARS-CoV-2 positive specimens collected from 3/1/2021 to 7/27/2021. Test-positive cases were matched 1:5 to test-negative controls on age, sex, race/ethnicity, and specimen collection date. Outcomes included SARS-CoV-2 infection and hospitalization. Exposures were 2 doses or 1 dose of mRNA-1273 [≥]14 days prior to specimen collection versus no COVID-19 vaccination. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, adjusting for confounders. VE was calculated as (1-odds ratio)x100%. ResultsThe study included 8,153 cases and their matched controls. Two-dose VE (95% confidence interval) was 86.7% (84.3-88.7%) against Delta infection, 98.4% (96.9-99.1%) against Alpha, 90.4% (73.9-96.5%) against Mu, 96-98% against other identified variants, and 79.9% (76.9-82.5%) against unidentified variants. VE against Delta declined from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged [≥]65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. ConclusionsTwo doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants. However, VE against Delta moderately declined with increasing time since vaccination. Trial Registration NumberNot applicable FundingModerna Inc.
Subject(s)
COVID-19 , Hepatitis DABSTRACT
Background: Phase 3 trials found mRNA-1273 was highly effective in preventing COVID-19. We conducted a prospective cohort study at Kaiser Permanente Southern California (KPSC) to determine the real-world vaccine effectiveness (VE) of mRNA-1273 in preventing COVID-19 diagnosis and severe disease.Methods: For this planned interim analysis, individuals aged ≥18 years receiving 2 doses of mRNA-1273 ≥24 days apart (12/18/2020-3/31/2021) were 1:1 matched with randomly selected unvaccinated individuals on age, sex, and race/ethnicity, with follow-up through 6/30/2021. Outcomes were COVID-19 diagnosis (SARS-CoV-2 positive molecular test or COVID-19 diagnosis code) or severe disease (COVID-19 hospitalization and COVID-19 hospital death). Adjusted hazard ratios (aHR) and confidence intervals (CI) were estimated by Cox proportional hazards models accounting for multiple comparisons. Adjusted VE was calculated as (1-aHR)x100. Whole genome sequencing was performed on SARS-CoV-2 positive specimens.Findings: This analysis included 352,878 recipients of 2 doses of mRNA-1273 matched to 352,878 unvaccinated individuals. VE (99·3% CI) against COVID-19 diagnosis was 87·4% (84·8-89·6%). VE against COVID-19 hospitalization and hospital death was 95·8% (90·7-98·1%) and 97·9% (66·9-99·9%), respectively. VE was higher against symptomatic (88·3% [98·3% CI: 86·1%-90·2%]) than asymptomatic COVID-19 (72·7% [53·4%-84·0%]), but was generally similar across age, sex, and racial/ethnic subgroups. VE among individuals with history of COVID-19 ranged from 8·2-33·6%. The most prevalent variants were Delta (47·1%), Alpha (21·4%), Gamma (11·4%), Epsilon (4·3%), and Iota (4·3%) among fully vaccinated individuals and Alpha (41·2%), Epsilon (18·2%), Delta (11·0%) and Gamma (8·6%) among unvaccinated individuals.Interpretation: These interim results provide reassuring evidence of the VE of 2 doses of mRNA-1273 across age, sex, and racial/ethnic subgroups, and against asymptomatic and symptomatic COVID-19, and severe COVID-19 outcomes. Among individuals with history of COVID-19, mRNA-1273 vaccination may offer added protection beyond immunity acquired from prior infection. Longer follow-up is needed to fully evaluate VE of mRNA-1273 against emerging SARS-CoV-2 variants.Funding: Moderna Inc.Declaration of Interests: KJB, LSS, LQ, BKA, YL, GSL, YT, AF, HST, JET, HFT are employees of Kaiser Permanente Southern California, which has been contracted by Moderna for the conduct of this present study. CAT is an employee of and a shareholder in Moderna Inc. KJB received funding from GlaxoSmithKline, Dynavax, Pfizer, Gilead, and Seqirus unrelated to this manuscript. LSS received funding from GlaxoSmithKline, Dynavax, and Seqirus unrelated to this manuscript. LQ received funding from GlaxoSmithKline and Dynavax unrelated to this manuscript. BKA received funding from GlaxoSmithKline, Dynavax, Seqirus and Pfizer unrelated to this manuscript. YL received funding from GlaxoSmithKline, Dynavax, Seqirus and Pfizer unrelated to this manuscript. GSL received funding from GlaxoSmithKline unrelated to this manuscript. YT received funding from GlaxoSmithKline unrelated to this manuscript. AF received funding from Pfizer, GlaxoSmithKline, CDC, and Gilead unrelated to this manuscript. HST received funding from GlaxoSmithKline, Pfizer, ALK, and Wellcome unrelated to this manuscript. JET received funding from Pfizer unrelated to this manuscript. HFT received funding from GlaxoSmithKline and Seqirus unrelated to this manuscript; HFT also served in advisory boards for Janssen and Pfizer.Ethics Approval Statement: The KPSC Institutional Review Board provided ethical approval for the study.