Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact firstname.lastname@example.org.
Real-World Effectiveness of the mRNA-1273 Vaccine Against COVID-19: Interim Results from a Prospective Observational Cohort Study
27 Pages Posted: 2 Sep 2021More...
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.
Note: This paper has been published: THE LANCET Regional Health Americas, November 25, 2021, DOI: https://doi.org/10.1016/j.lana.2021.100134
Keywords: COVID-19, SARS-CoV-2, mRNA-1273, vaccine effectiveness, variants, matched cohort
Suggested Citation: Suggested Citation