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.

Objectives To 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. Design Test negative case-control study. Setting Kaiser Permanente Southern California (KPSC), an integrated healthcare system. Participants Adult 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. Interventions Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination. Main outcome measures Outcomes 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%. Results The 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. Conclusions Two 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.

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This study examines the effect of a home visiting intervention on maternal alcohol use, problematic drinking, and the association of home visiting and alcohol use on children's behavioral, cognitive, and health outcomes at 5 time points over 5 years. Method: We analyzed 5,099 observations of 1,236 mothers and their children from pregnancy to 5 years postbirth, within a longitudinal clusterrandomized trial evaluating the effect of a home visiting intervention on mothers in Cape Town, South Africa. Paraprofessional home visitors coached mothers on coping with multiple risk factors, including a brief, 1-visit intervention on alcohol prevention in pregnancy. We assessed changes in maternal drinking over time in relation to the intervention, and then examined the impact of these drinking patterns on child outcomes over five years. Results: Drinking increased over the 5 years postbirth, but it was significantly lower in the intervention condition. Compared with abstinence, mothers' problematic drinking was associated with decreased child weight (Ϫ0.21 z-units) at all assessments, increased child aggressive behavior (3 to 7 additional symptoms), and decreased child performance on an executive functioning measure (the silly sounds task; odds ratio ϭ .34) at 3 and 5 years. The intervention's effect was associated with increased child aggression (0.25 to 0.75 of 1 additional symptom), but the intervention appeared to decrease the effect of problem drinking on children's aggressive acts and executive functioning. Conclusion: These findings support the need for sustained interventions to reduce alcohol use, especially for mothers who exhibit problematic drinking. Maternal drinking influences children's health and development over time. What is the public health significance of this article?This study highlights the need for home visiting programs that address maternal drinking during pregnancy and early childhood. Even brief alcohol interventions, nested within a generalist home visiting intervention, result in less problematic drinking over the next 5 years. The findings demonstrate that problematic alcohol use is associated with children's increased challenge to maintain healthy growth, inhibitory control, and nonaggressive behavior overtime.

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against omicron BA.4/BA.5 compared with earlier omicron subvariants. This test-negative case–control study evaluates mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron subvariants. The study includes 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 is high and wanes slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection is initially moderate to high (61.0%-90.6% 14-30 days post third dose) and wanes rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranges between 64.3%-75.7%, and is 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 is 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 is 88.5%. Evaluation of the updated bivalent booster is warranted.