Analysis of mRNA COVID-19 Vaccine Uptake Among Immunocompromised Individuals in a Large US Health System.

Importance: Immunocompromised individuals are at increased risk for severe outcomes due to SARS-CoV-2 infection. Given the varying and complex nature of COVID-19 vaccination recommendations, it is important to understand COVID-19 vaccine uptake in this vulnerable population. Objective: To assess mRNA COVID-19 vaccine uptake and factors associated with uptake among immunocompromised individuals from December 14, 2020, through August 6, 2022. Design, Setting, and Participants: This cohort study was conducted with patients of Kaiser Permanente Southern California (KPSC), an integrated health care system in the US. The study included patients aged 18 years or older who were immunocompromised (individuals with an immunocompromising condition or patients who received immunosuppressive medications in the year prior to December 14, 2020) and still met criteria for being immunocompromised 1 year later. Exposures: Age, sex, self-identified race and ethnicity, prior positive COVID-19 test result, immunocompromising condition, immunomodulating medication, comorbidities, health care utilization, and neighborhood median income. Main Outcomes and Measures: Outcomes were the number of doses of mRNA COVID-19 vaccine received and the factors associated with receipt of at least 4 doses, estimated by hazard ratios (HRs) and 95% Wald CIs via Cox proportional hazards regression. Statistical analyses were conducted between August 9 and 23, 2022. Results: Overall, 42 697 immunocompromised individuals met the study eligibility criteria. Among these, 18 789 (44.0%) were aged 65 years or older; 20 061 (47.0%) were women and 22 635 (53.0%) were men. With regard to race and ethnicity, 4295 participants (10.1%) identified as Asian or Pacific Islander, 5174 (12.1%) as Black, 14 289 (33.5%) as Hispanic, and 17 902 (41.9%) as White. As of the end of the study period and after accounting for participant censoring due to death or disenrollment from the KPSC health plan, 78.0% of immunocompromised individuals had received a third dose of mRNA COVID-19 vaccine. Only 41.0% had received a fourth dose, which corresponds to a primary series and a monovalent booster dose for immunocompromised individuals. Uptake of a fifth dose was only 0.9% following the US Centers for Disease Control and Prevention (CDC) recommendation to receive a second monovalent booster (ie, fifth dose). Adults aged 65 years or older (HR, 3.95 [95% CI, 3.70-4.22]) were more likely to receive at least 4 doses compared with those aged 18 to 44 years or 45 to 64 years (2.52 [2.36-2.69]). Hispanic and non-Hispanic Black adults (HR, 0.77 [95% CI, 0.74-0.80] and 0.82 [0.78-0.87], respectively, compared with non-Hispanic White adults), individuals with prior documented SARS-CoV-2 infection (0.71 [0.62-0.81] compared with those without), and individuals receiving high-dose corticosteroids (0.88 [0.81-0.95] compared with those who were not) were less likely to receive at least 4 doses. Conclusions and Relevance: These findings suggest that adherence to CDC mRNA monovalent COVID-19 booster dose recommendations among immunocompromised individuals was low. Given the increased risk for severe COVID-19 in this vulnerable population and the well-established additional protection afforded by booster doses, targeted and tailored efforts to ensure that immunocompromised individuals remain up to date with COVID-19 booster dose recommendations are warranted.

Effectiveness Associated With BNT162b2 Vaccine Against Emergency Department and Urgent Care Encounters for Delta and Omicron SARS-CoV-2 Infection Among Adolescents Aged 12 to 17 Years.

Importance: Data about the duration of protection of 2 and 3 doses of BNT162b2 in children and adolescents are needed to help inform recommendations for boosters in this age group. Objective: To evaluate vaccine effectiveness (VE) and durability associated with 2 doses of BNT162b2 against Delta- and Omicron-related emergency department (ED) and urgent care (UC) encounters among adolescents aged 12 to 17 years and to estimate VE associated with 3 doses against these same outcomes. Design, Setting, and Participants: This test-negative case-control study was conducted at Kaiser Permanente Southern California, an integrated health care system using electronic health records in the US. Participants included Kaiser Permanente Southern California members ages 12 to 17 years with an ED or UC encounter from November 1, 2021, through March 18, 2022, for acute respiratory infection who were tested for SARS-CoV-2 via a reverse transction-polymerase chain reaction test. Analyses were conducted from March 21 to June 22, 2022. Exposures: BNT162b2 vaccination status ascertained from electronic health records and state registry data. Main Outcomes and Measures: The main outcome was VE associated with BNT162b2 against ED and UC encounters related to Delta or Omicron variant SARS-CoV-2 infection. Results: Analyses were conducted among 3168 adolescents, including 1004 with ED visits and 2164 with UC visits. Median (IQR) age was 15 (13-16) years, and 1461 (46.1%) were boys. In adjusted analyses, VE associated with 2 doses of BNT162b2 against ED or UC encounters was highest within the first 2 months for both Delta (89% [95% CI, 69% to 96%]) and Omicron (73% [95% CI, 54% to 84%]) variants but waned to 49% (95% CI, 27% to 65%) for the Delta variant and 16% (95% CI, -7% to 34%) for the Omicron variant at 6 months and beyond. A third dose of BNT162b2 was associated with improved protection against the Omicron variant (87% [95% CI, 72% to 94%]) after a median (IQR) of 19 (9-32) days after dose 3. Conclusions and Relevance: These findings suggest that 2 doses of the BNT162b2 COVID-19 vaccine were associated with high levels of protection against ED and UC encounters related to the Delta and Omicron variants of SARS-CoV-2 in the first few months after vaccination. However, effectiveness waned over time, especially against Omicron. A third dose of BNT162b2 was associated with improved protection against Omicron beyond that seen initially after 2 doses, underscoring the importance of boosters for adolescents aged 12 to 17 years.

Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case-control study.

BACKGROUND: The duration of protection against the omicron (B.1.1.529) variant for current COVID-19 vaccines is not well characterised. Vaccine-specific estimates are especially needed. We aimed to evaluate the effectiveness and durability of two and three doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine against hospital and emergency department admissions due to the delta (B.1.617.2) and omicron variants. METHODS: In this case-control study with a test-negative design, we analysed electronic health records of members of Kaiser Permanente Southern California (KPSC), a large integrated health system in California, USA, from Dec 1, 2021, to Feb 6, 2022. Vaccine effectiveness was calculated in KPSC patients aged 18 years and older admitted to hospital or an emergency department (without a subsequent hospital admission) with a diagnosis of acute respiratory infection and tested for SARS-CoV-2 via PCR. Adjusted vaccine effectiveness was estimated with odds ratios from adjusted logistic regression models. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were done for 11 123 hospital or emergency department admissions. In adjusted analyses, effectiveness of two doses of the BNT162b2 vaccine against the omicron variant was 41% (95% CI 21-55) against hospital admission and 31% (16-43) against emergency department admission at 9 months or longer after the second dose. After three doses, effectiveness of BNT162b2 against hospital admission due to the omicron variant was 85% (95% CI 80-89) at less than 3 months but fell to 55% (28-71) at 3 months or longer, although confidence intervals were wide for the latter estimate. Against emergency department admission, the effectiveness of three doses of BNT162b2 against the omicron variant was 77% (72-81) at less than 3 months but fell to 53% (36-66) at 3 months or longer. Trends in waning against SARS-CoV-2 outcomes due to the delta variant were generally similar, but with higher effectiveness estimates at each timepoint than those seen for the omicron variant. INTERPRETATION: Three doses of BNT162b2 conferred high protection against hospital and emergency department admission due to both the delta and omicron variants in the first 3 months after vaccination. However, 3 months after receipt of a third dose, waning was apparent against SARS-CoV-2 outcomes due to the omicron variant, including hospital admission. Additional doses of current, adapted, or novel COVD-19 vaccines might be needed to maintain high levels of protection against subsequent waves of SARS-CoV-2 caused by the omicron variant or future variants with similar escape potential. FUNDING: Pfizer.

Incidence and Estimated Vaccine Effectiveness Against Hospitalizations for All-Cause Pneumonia Among Older US Adults Who Were Vaccinated and Not Vaccinated With 13-Valent Pneumococcal Conjugate Vaccine.

Importance: Following routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010, invasive pneumococcal disease rates have decreased substantially in children and adults. In 2014, the Advisory Committee for Immunization Practices recommended routine use of PCV13 among adults aged 65 years or older; previously only 23-valent pneumococcal polysaccharide vaccine (PPV23) was recommended. Objective: To estimate the association between the incidence of hospitalized all-cause pneumonia and lower respiratory tract infections (LRTI) and PCV13 vaccination among older adults at Kaiser Permanente Northern California (KPNC). Design, Setting, and Participants: This retrospective cohort study included adults at KPNC aged 65 years or older between July 1, 2015, and June 30, 2018, born after 1936 with no known history of PPV23 or PCV13 receipt before age 65. The study took place at an integrated health care system with an annual membership more than 4 million individuals, approximately 15% of whom are 65 years or older and broadly representative of the region. Data analysis took place from July 2018 to December 2021, and data collection took place from November 2016 to June 2018. Exposures: PCV13 vaccination status was ascertained from the electronic medical record (EMR). Individuals were considered vaccinated 14 days following immunization. Main Outcomes and Measures: First hospitalized all-cause pneumonia was identified in the EMR using primary/secondary discharge diagnosis International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. First hospitalized LRTI was identified using pneumonia codes and acute bronchitis codes. Relative risk (RR) of first pneumonia or LRTI hospitalization of individuals who were PCV13 vaccinated vs PCV13 unvaccinated was estimated using Poisson regressions adjusted for sex, race, ethnicity, age, influenza vaccine receipt, PPV23 receipt since age 65, pneumonia risk factors, health care use, and season. Vaccine effectiveness (VE) was estimated as (1-RR) × 100%. Results: Of 192 061 adults, 107 957 (56%) were female and 139 024 (72%) were White individuals. PCV13 coverage increased from 0 in 2014 to 135 608 (76.9%) by 2018. There were 3488 individuals with 3766 pneumonia hospitalizations and 3846 individuals with 4173 LRTI hospitalizations. PCV13 was associated with an adjusted VE of 10.0% (95% CI, 2.4-17.0; P = .01) against hospitalized pneumonia and 9.4% (95% CI, 2.1-16.1; P = .01) against hospitalized LRTI. Conclusions and Relevance: In the context of a robust pediatric PCV13 immunization program, PCV13 vaccination of adults aged 65 years or older was associated with significant reductions in hospitalizations for all-cause pneumonia and LRTI. Vaccinating older adults with PCVs may provide broader public health benefit against pneumonia hospitalizations.

Effectiveness of a third dose of BNT162b2 mRNA COVID-19 vaccine in a large US health system: A retrospective cohort study.

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.

Distribution of SARS-CoV-2 Variants in a Large Integrated Health Care System - California, March-July 2021.

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.

Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study.

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.

Effects of tomato- and soy-rich diets on the IGF-I hormonal network: a crossover study of postmenopausal women at high risk for breast cancer.

To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone-binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 µmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 µmol/L (P < 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted.