Search

Background We conducted a prospective cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of a booster dose vs 2-dose primary series of messenger RNA (mRNA)-1273 in immunocompetent individuals. Methods Immunocompetent adults who received a booster dose of mRNA-1273 from October 2021 through December 2021 were matched 1:1 to randomly selected 2-dose mRNA-1273 recipients by age, sex, race/ethnicity, and second-dose date and followed up through January 2022. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), comparing outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and coronavirus disease 2019 [COVID-19] hospitalization and hospital death) in the booster-dose and 2-dose groups. Adjusted rVE (%) was calculated as (1 − aHR) × 100. aHRs and rVE were also estimated by subgroup and month of follow-up. Results The study included 431 328 booster-dose vaccinated adults matched to 431 328 2-dose vaccinated adults. rVE was 61.3% (95% CI: 60.5%–62.2%) against SARS-CoV-2 infection, 89.0% (86.2%–91.2%) against COVID-19 hospitalization, and 96.0% (68.0%–99.5%) against COVID-19 hospital death. rVE against SARS-CoV-2 infection ranged from 55.6% to 66.7% across all subgroups. rVE against SARS-CoV-2 infection decreased from 67.1% (0 to Conclusions Among immunocompetent adults, the mRNA-1273 booster conferred additional protection against SARS-CoV-2 infection and severe COVID-19 disease compared with the 2-dose mRNA-1273 primary series during periods of Delta and Omicron predominance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case–control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron or Delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variants determined by S gene target failure status (16% Delta and 84% Omicron). The two-dose VE against Omicron infection at 14–90 days was 44.0% (95% confidence interval, 35.1–51.6%) but declined quickly. The three-dose VE was 93.7% (92.2–94.9%) and 86.0% (78.1–91.1%) against Delta infection and 71.6% (69.7–73.4%) and 47.4% (40.5–53.5%) against Omicron infection at 14–60 days and >60 days, respectively. The three-dose VE was 29.4% (0.3–50.0%) against Omicron infection in immunocompromised individuals. The three-dose VE against hospitalization with Delta or Omicron was >99% across the entire study population. Our findings demonstrate high, durable three-dose VE against Delta infection but lower effectiveness against Omicron infection, particularly among immunocompromised people. However, three-dose VE of mRNA-1273 was high against hospitalization with Delta and Omicron variants.

Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.† Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4-7). This study used whole genome sequencing (WGS) data on SARS-CoV-2-positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4-July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2-positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4-May 19, 2021. During April 15-July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4-July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18-44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States.

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.

A prospective cohort study at Kaiser Permanente Southern California was conducted to evaluate the relative vaccine effectiveness (rVE) of a booster-dose vs. 2-dose primary series of mRNA-1273 in immunocompetent individuals during periods of Delta and Omicron predominance.Immunocompetent adults who received a booster dose of mRNA-1273 from October through December 2021 were matched 1:1 to randomly selected 2-dose mRNA-1273 recipients by age, sex, race/ethnicity, and second dose date, and followed up through January 2022. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs), comparing outcomes (SARS-CoV-2 infection, and COVID-19 hospitalization and hospital death) in the booster-dose and 2-dose groups. Adjusted rVE (%) was calculated as (1-aHR)x100. aHRs and rVEs were also estimated for SARS-CoV-2 infection by subgroups (age, sex, race/ethnicity, history of SARS-CoV-2 infection, pregnancy, chronic diseases), and for SARS-CoV-2 infection and severe COVID-19 disease by month of follow-up.The study included 431,328 booster-dose vaccinated adults matched to 431,328 2-dose vaccinated adults. rVE was 61.3% (95%CI: 60.5-62.2%) against SARS-CoV-2 infection, 89.0% (86.2-91.2%) against COVID-19 hospitalization, and 96.0% (68.0-99.5%) against COVID-19 hospital death. rVE against SARS-CoV-2 infection ranged from 55.6% to 66.7% across all subgroups. rVE against SARS-CoV-2 infection decreased from 67.1% (0-1 month of follow-up) to 30.5% (2-3 months). For COVID-19 hospitalization, rVE decreased from 91.2% (0-1 month) to 78.7% (2-3 months).Among immunocompetent adults, the mRNA-1273 booster conferred additional protection against SARS-CoV-2 infection and severe COVID-19 disease compared to the 2-dose mRNA-1273 primary series during periods of Delta and Omicron predominance.

A web-based survey was widely distributed between November 1

BackgroundWe 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.MethodsThe 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-Results927,004 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-ConclusionsThese 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.SummaryThis prospective cohort study provides evidence for continued protection of 2 doses of mRNA-1273 against SARS-CoV-2 infection over 8 months post-vaccination and during the Delta period. VE against COVID-19 hospitalization remained robust and stable over the same period.

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.

ObjectivesTo evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination.DesignTest negative case-control study.SettingKaiser Permanente Southern California (KPSC), an integrated healthcare system.ParticipantsAdult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021.InterventionsTwo dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination.Main outcome measuresOutcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1–odds ratio)×100%.ResultsThe study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta.ConclusionsTwo doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.

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 applicableFundingModerna Inc.