Background Vaccine effectiveness studies have not differentiated the effect of the delta (B.1.617.2) variant and potential waning immunity in observed reductions in effectiveness against SARS-CoV-2 infections. We aimed to evaluate overall and variant-specific effectiveness of BNT162b2 (tozinameran, Pfizer–BioNTech) against SARS-CoV-2 infections and COVID-19-related hospital admissions by time since vaccination among members of a large US health-care system. Methods In this retrospective cohort study, we analysed electronic health records of individuals (≥12 years) who were members of the health-care organisation Kaiser Permanente Southern California (CA, USA), to assess BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions for up to 6 months. Participants were required to have 1 year or more previous membership of the organisation. Outcomes comprised SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions. Effectiveness calculations were based on hazard ratios from adjusted Cox models. This study was registered with ClinicalTrials.gov , NCT04848584 . Findings Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 (median age 45 years [IQR 29–61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72–74) and against COVID-19-related hospital admissions was 90% (89–92). Effectiveness against infections declined from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85–97]) but declined to 53% [39–65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95–99), but waned to 67% (45–80) at 4–5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84–96]) up to 6 months. Interpretation Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection. Funding Pfizer.

Emerging reports suggest that obese patients who are hospitalized with COVID-19 may have worse outcomes; whether this association extends to those who are not hospitalized is unclear. This study examines the association between obesity and death 21 days after diagnosis of COVID-19 among patients who receive care in an integrated health care system, accounting for obesity-related comorbidities and sociodemographic factors.

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Background: The Omicron (B.1.1.529) variant of SARS-CoV-2 has rapidly achieved global dissemination, accounting for most infections in the United States by December 2021. Risk of severe outcomes associated with Omicron infections, as compared to earlier SARS-CoV-2 variants, remains unclear. Methods: We analyzed clinical and epidemiologic data from cases testing positive for SARS-CoV-2 infection within the Kaiser Permanente Southern California healthcare system from November 30, 2021 to January 1, 2022, using S gene target failure (SGTF) as assessed by the ThermoFisher TaqPath ComboKit assay as a proxy for Omicron infection. We fit Cox proportional hazards models to compare time to any hospital admission and hospital admissions associated with new-onset respiratory symptoms, intensive care unit (ICU) admission, mechanical ventilation, and mortality among cases with Omicron and Delta (non-SGTF) variant infections. We fit parametric competing risk models to compare lengths of hospital stay among admitted cases with Omicron and Delta variant infections. Results: Our analyses included 52,297 cases with SGTF (Omicron) and 16,982 cases with non-SGTF (Delta [B.1.617.2]) infections, respectively. Hospital admissions occurred among 235 (0.5%) and 222 (1.3%) of cases with Omicron and Delta variant infections, respectively. Among cases first tested in outpatient settings, the adjusted hazard ratios for any subsequent hospital admission and symptomatic hospital admission associated with Omicron variant infection were 0.48 (0.36-0.64) and 0.47 (0.35-0.62), respectively. Rates of ICU admission and mortality after an outpatient positive test were 0.26 (0.10-0.73) and 0.09 (0.01-0.75) fold as high among cases with Omicron variant infection as compared to cases with Delta variant infection. Zero cases with Omicron variant infection received mechanical ventilation, as compared to 11 cases with Delta variant infections throughout the period of follow-up (two-sided p<0.001). Median duration of hospital stay was 3.4 (2.8-4.1) days shorter for hospitalized cases with Omicron variant infections as compared to hospitalized patients with Delta variant infections, reflecting a 69.6% (64.0-74.5%) reduction in hospital length of stay. Conclusions: During a period with mixed Delta and Omicron variant circulation, SARS-CoV-2 infections with presumed Omicron variant infection were associated with substantially reduced risk of severe clinical endpoints and shorter durations of hospital stay.

Background Globally, recommendations are expanding for third (booster) doses of BNT162b2 (Pfizer–BioNTech). In the United States, as of November 19, 2021, boosters were recommended for all adults aged 18 years and older. We evaluated the effectiveness of a third dose of BNT162b2 among adults in a large US integrated health system. Methods In this retrospective cohort study, we analyzed electronic health records from Kaiser Permanente Southern California between Dec 14, 2020 and Dec 5, 2021 to assess vaccine effectiveness (VE) of two and three doses of BNT162b2 against SARS-CoV-2 infections (without hospital admission) andCOVID-19-related hospital admission. VE was calculated using hazards ratios from adjusted Cox models. Findings After only two doses, VE against infection declined from 85% (95% CI 83–86) during the first month to 49% (46–51) ≥ 7 months following vaccination. Overall VE against hospitalization was 90% (95% CI 86–92) within one month and did not wane, however, effectiveness against hospitalization appeared to wane among immunocompromised individuals but was not statistically significant (93% [72–98] at 1 month to 74% [45–88] after ≥ 7 months; p=0·490). Three-dose VE (median follow-up 1·3 months [SD 0·6]) was 88% (95% CI 86–89) against infection and 97% (95–98) against hospitalization. Effectiveness after three doses was higher than that seen one month after receiving only two doses for both outcomes. Relative VE of three doses compared to two (with at least six months after the second dose) was 75% (95% CI 71−78) against infections and 70% (48−83) against hospital admissions. Interpretation These data support the benefit of broad BNT162b2 booster recommendations, as three doses confers comparable, if not better, protection against SARS-CoV-2 infections and hospital admission as was seen soon after receiving two doses. Funding Pfizer Inc.