Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages.

Emerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14-60 days and 121-180 days was 52.7% (46.9-57.8%) and 35.5% (-2.8-59.5%) for infection, and 59.3% (49.7-67.0%) and 33.2% (-28.2-68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9-85.1%) and 52.0% (-1.2-77.3%) at 14-60 days and 61-120 days, respectively. rVE against XBB at 14-60 days and 121-180 days was 48.8% (33.4-60.7%) and -3.9% (-18.1-11.3%) for infection, 70.7% (52.4-82.0%) and 15.7% (-6.0-33.2%) for ED/UC encounters, and 87.9% (43.8-97.4%) and 57.1% (17.0-77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

Real-world effectiveness of recombinant zoster vaccine in self-identified Chinese individuals aged ≥50 years in the United States.

We evaluated the vaccine effectiveness (VE) of two doses of recombinant zoster vaccine (RZV) against herpes zoster (HZ) and postherpetic neuralgia (PHN) in Chinese adults at Kaiser Permanente Southern California (KPSC). Chinese KPSC members were identified based on self-reported ethnicity or self-reported preferred spoken/written language. Those aged ≥50 years who received two doses of RZV 4 weeks to ≤ 6 months apart were matched 1:4 to RZV unvaccinated Chinese members and followed through June 2022; second doses were accrued 6/1/2018-12/31/2020. We estimated incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) comparing outcomes (HZ and PHN). Adjusted VE (%) was calculated as (1-aHR)×100. 3978 RZV vaccinated Chinese members were matched to 15,912 RZV unvaccinated Chinese members. The incidence per 1000 person-years (95% CI) of HZ in the vaccinated group was 1.5 (0.9-2.5) and 10.9 (9.8-12.1) in the unvaccinated group; aHR (95% CI) was 0.12 (0.07-0.21). Adjusted VE (95% CI) was 87.6% (78.9-92.7) against HZ. We identified 0 PHN cases in the vaccinated group and 19 in the unvaccinated group. Among Chinese adults aged ≥50 years, two doses of RZV provided substantial protection against HZ and PHN supporting the real-world effectiveness of the vaccine in this population.

Mortality risk after COVID-19 vaccination: A self-controlled case series study.

BACKGROUND: Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. METHODS: We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. RESULTS: For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. CONCLUSION: Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.

Influenza vaccination coverage among persons ages six months and older in the Vaccine Safety Datalink in the 2017-18 through 2022-23 influenza seasons.

BACKGROUND: In the United States, annual vaccination against seasonal influenza is recommended for all people ages ≥ 6 months. Vaccination coverage assessments can identify populations less protected from influenza morbidity and mortality and help to tailor vaccination efforts. Within the Vaccine Safety Datalink population ages ≥ 6 months, we report influenza vaccination coverage for the 2017-18 through 2022-23 seasons. METHODS: Across eight health systems, we identified influenza vaccines administered from August 1 through March 31 for each season using electronic health records linked to immunization registries. Crude vaccination coverage was described for each season, overall and by self-reported sex; age group; self-reported race and ethnicity; and number of separate categories of diagnoses associated with increased risk of severe illness and complications from influenza (hereafter referred to as high-risk conditions). High-risk conditions were assessed using ICD-10-CM diagnosis codes assigned in the year preceding each influenza season. RESULTS: Among individual cohorts of more than 12 million individuals each season, overall influenza vaccination coverage increased from 41.9 % in the 2017-18 season to a peak of 46.2 % in 2019-20, prior to declaration of the COVID-19 pandemic. Coverage declined over the next three seasons, coincident with widespread SARS-CoV-2 circulation, to a low of 40.3 % in the 2022-23 season. In each of the six seasons, coverage was lowest among males, 18-49-year-olds, non-Hispanic Black people, and those with no high-risk conditions. While decreases in coverage were present in all age groups, the declines were most substantial among children: 2022-23 season coverage for children ages six months through 8 years and 9-17 years was 24.5 % and 22.4 % (14 and 10 absolute percentage points), respectively, less than peak coverage achieved in the 2019-20 season. CONCLUSIONS: Crude influenza vaccination coverage increased from 2017 to 18 through 2019-20, then decreased to the lowest level in the 2022-23 season. In this insured population, we identified persistent disparities in influenza vaccination coverage by sex, age, and race and ethnicity. The overall low coverage, disparities in coverage, and recent decreases in coverage are significant public health concerns.

mRNA-1273 bivalent (original and Omicron) COVID-19 vaccine effectiveness against COVID-19 outcomes in the United States.

The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received ≥2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%-75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable ≥3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%-58.8%) and 82.7% (63.7%-91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.

Risk of herpes zoster following mRNA COVID-19 vaccine administration.

BACKGROUND: Adverse events following mRNA COVID-19 vaccines, including herpes zoster (HZ), have been reported. We conducted a cohort study to evaluate the association between mRNA COVID-19 vaccination and subsequent HZ at Kaiser Permanente Southern California (KPSC). RESEARCH DESIGN AND METHODS: The vaccinated cohort consisted of KPSC members who received their first dose of mRNA COVID-19 vaccine (mRNA-1273 and BNT162b2) during 12/2020-05/2021 and were matched to unvaccinated individuals on age and sex. Incident HZ cases occurring within 90 days of follow-up were identified by diagnosis codes and antiviral medications. Cox proportional hazards models estimated adjusted hazard ratios (aHR), comparing HZ incidence between the vaccinated and unvaccinated cohorts. RESULTS: Cohort included 1,052,362 mRNA-1273 recipients, 1,055,461 BNT162b2 recipients, and 1,020,334 comparators. Compared to unvaccinated individuals, aHR for HZ up to 90 days after the second dose of mRNA-1273 and BNT162b2 was 1.14 (1.05-1.24) and 1.12 (1.03-1.22), respectively. In those aged ≥50 years not vaccinated with zoster vaccine, aHR was also increased after the second dose of mRNA-1273 (1.18 [1.06-1.33]) and BNT162b2 (1.15 [1.02-1.29]) vaccine vs. unvaccinated individuals. CONCLUSIONS: Our findings suggest a potential increased risk of HZ after a second dose of mRNA vaccines, potentially driven by the increased risk in individuals aged ≥50 years without history of zoster vaccination.

Timely Prenatal and Infant Pertussis Vaccine Uptake in an Integrated Health System.

BACKGROUND: Hispanic infants bear the burden of pertussis infection. We examined pertussis protection from vaccination in infants with US-born and foreign-born Hispanic mothers. METHODS: Retrospective cohort study of infants up to 1 year of age. Secondary data of mothers with continuous membership since the 27th week of pregnancy with infants born 1/1/2012-12/31/2017 in an integrated health care delivery organization, which broadly represent the Southern California population. RESULTS: Foreign-born Hispanic mothers had higher prenatal tetanus, diphtheria, acellular pertussis (Tdap) uptake compared to US-born white mothers [adjusted risk ratio (aRR): 1.04, 95% confidence interval (CI): 1.03, 1.05]. Infants with mothers on Medicaid insurance disproportionately did not enroll in the health plan by the time they were eligible for their first dose of the DTaP vaccine (68.4%). Once initiating the infant vaccine series, foreign-born Hispanic mothers more likely adhered than US-born white mothers (aRR: 1.05, CI: 1.02, 1.08). DISCUSSION: In an integrated health system, disparities in vaccine uptake can be minimized. Infants who are born to mothers with Medicaid insurance and are not enrolled in the health plan after birth may be under-protected from pertussis.

Incidence and clinical outcomes of pneumonia in persons with down syndrome in the United States.

BACKGROUND: Persons with Down syndrome (DS) experience an increased risk of pneumonia. We determined the incidence and outcomes of pneumonia and relationship to underlying comorbidities in persons with and without DS in the United States. METHODS: This retrospective matched cohort study used de-identified administrative claims data from Optum. Persons with DS were matched 1:4 to persons without DS on age, sex, and race/ethnicity. Pneumonia episodes were analyzed for incidence, rate ratios and 95 % confidence intervals, clinical outcomes, and comorbidities. RESULTS: During 1-year follow-up among 33796 persons with and 135184 without DS, the incidence of all-cause pneumonia (pneumonia) was substantially higher among people with DS than those without DS (12427 vs. 2531 episodes/100000 person-years; 4.7-5.7 fold increase). Persons with DS and pneumonia were more likely to be hospitalized (39.4 % vs. 13.9 %) or admitted to the ICU (16.8 % vs. 4.8 %). Mortality was higher 1 year after first pneumonia (5.7 % vs. 2.4 %; P < 0.0001). Results were similar for episodes of pneumococcal pneumonia. Specific comorbidities were associated with pneumonia, particularly heart disease in children and neurologic disease in adults, which only partially mediated the effect of DS on pneumonia. CONCLUSIONS: Among persons with DS, incidence of pneumonia and associated hospitalizations were increased; mortality among those with pneumonia was comparable at 30 days, but higher at 1 year. DS should be considered an independent risk condition for pneumonia.

Effectiveness of a fourth dose of mRNA-1273 against COVID-19 among older adults in the United States: Interim results from an observational cohort study.

We evaluated relative vaccine effectiveness (rVE) of 4- vs. 3-dose mRNA-1273 against SARS-CoV-2 infection, and COVID-19 hospitalization and death in immunocompetent adults aged ≥50 years at Kaiser Permanente Southern California. We included 178,492 individuals who received a fourth dose of mRNA-1273, and 178,492 randomly selected 3-dose recipients who were matched to 4-dose recipients by age, sex, race/ethnicity, and third dose date. Adjusted 4- vs. 3-dose rVE against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospitalization death were 25.9 % (23.5 %, 28.2 %), 67.3 % (58.7 %, 74.1 %), and 72.5 % (-35.9 %, 95.2 %), respectively. Adjusted rVE against SARS-CoV-2 infection ranged between 19.8 % and 39.1 % across subgroups. Adjusted rVE against SARS-CoV-2 infection and COVID-19 hospitalization decreased 2-4 months after the fourth dose. Four mRNA-1273 doses provided significant protection against COVID-19 outcomes compared with 3 doses, consistent in various subgroups of demographic and clinical characteristics, although rVE varied and waned over time.

Vaccine effectiveness of the mRNA-1273 3-dose primary series against COVID-19 in an immunocompromised population: A prospective observational cohort study.

BACKGROUND: Data on the effectiveness of the 3-dose mRNA-1273 primary series are limited, particularly in comparison to 2 doses. Given suboptimal COVID-19 vaccine uptake among immunocompromised populations, it is important to monitor the effectiveness of fewer than the recommended doses in this population. METHODS: We conducted a matched cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of the 3-dose series vs 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 outcomes among immunocompromised individuals. RESULTS: We included 21,942 3-dose recipients who were 1:1 matched with randomly selected 2-dose recipients (third doses accrued 08/12/2021-12/31/2021, with follow-up through 01/31/2022). Adjusted rVE of 3 vs 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0 % (95 % CI: 50.8-58.9 %), 83.0 % (75.4-88.3 %), and 87.1 % (30.6-97.6 %), respectively. CONCLUSION: Three doses of mRNA-1273 were associated with a significantly higher rVE against SARS-CoV-2 infection and severe outcomes, compared to 2 doses. These findings were consistent across subgroups of demographic and clinical characteristics, and mostly consistent across subgroups of immunocompromising conditions. Our study highlights the importance of completing the 3-dose series for immunocompromised populations.

Impact of a Statewide Livestock Antibiotic Use Policy on Resistance in Human Urine Escherichia coli Isolates: A Synthetic Control Analysis.

BACKGROUND: On 1 January 2018, California implemented Senate Bill 27 (SB27), banning, for the first time in the United States, routine preventive use of antibiotics in food-animal production and any antibiotic use without a veterinarian's prescription. OBJECTIVES: Our objective was to assess whether SB27 was associated with decreased antimicrobial resistance among E. coli isolated from human urine. METHODS: We used U.S. nationwide monthly state-level data from BD Insights Research Database (Becton, Dickinson, and Co.) spanning 1 January 2013 to 30 June 2021 on antibiotic-resistance patterns of 30-d nonduplicate E. coli isolated from urine. Tested antibiotic classes included aminoglycosides, extended-spectrum cephalosporins (ESC), fluoroquinolones, and tetracyclines. Counts of tested and not-susceptible (resistant and intermediate, hereafter resistant) urine isolates were available by sex, age group (<65, 65+ year), month, and state. We applied a synthetic control approach to estimate the causal effect of SB27 on resistance patterns. Our approach created a synthetic California based on a composite of other states without the policy change and contrasted its counterfactual postpolicy trends with the observed postpolicy trends in California. FINDINGS: We included 7.1 million E. coli urine isolates, 90% among women, across 33 states. From 2013 to 2017, the median (interquartile range) resistance percentages in California were 11.9% (7.4, 17.6), 13.8% (5.8, 20.0), 24.6% (9.6, 36.4), 7.9% (2.1, 13.1), for aminoglycosides, ESC, fluoroquinolones, and tetracyclines, respectively. SB27 was associated with a 7.1% reduction in ESC resistance (p-value for joint null: <0.01), but no change in resistance to aminoglycosides, fluoroquinolones, or tetracyclines. DISCUSSION: Further research is needed to determine the role of SB27 in the observed reduction in ESC resistance E. coli in human populations, particularly as additional states implement similar legislation. https://doi.org/10.1289/EHP11221.

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 of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5.

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.

Prevention of Neisseria gonorrhoeae With Meningococcal B Vaccine: A Matched Cohort Study in Southern California.

BACKGROUND: Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea. METHODS: We conducted a matched cohort study from 2016 to 2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non-OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, and Y (MenACWY) who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome. RESULTS: The study included 6641 recipients of 4CMenB matched to 26 471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% confidence intervals [CIs]) were 2.0 (1.3-2.8) for recipients of 4CMenB and 5.2 (4.6-5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (hazard ratio [HR], 0.54; 95% CI, .34-.86), but chlamydia rates were similar between vaccine groups (HR, 0.98; 95% CI, .82-1.17). CONCLUSIONS: These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.

Active Postlicensure Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data.

Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013-2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018-2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed.

Effectiveness of Messenger RNA-1273 Vaccine Booster Against Coronavirus Disease 2019 in Immunocompetent Adults.

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 <1 month of follow-up) to 30.5% (2 to <3 months). For COVID-19 hospitalization, rVE decreased from 91.2% (0 to <1 month) to 78.7% (2 to <3 months). 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.

A safety study evaluating non-COVID-19 mortality risk following COVID-19 vaccination.

BACKGROUND: The safety of COVID-19 vaccines plays an important role in addressing vaccine hesitancy. We conducted a large cohort study to evaluate the risk of non-COVID-19 mortality after COVID-19 vaccination while adjusting for confounders including individual-level demographics, clinical risk factors, health care utilization, and community-level socioeconomic risk factors. METHODS: The retrospective cohort study consisted of members from seven Vaccine Safety Datalink sites from December 14, 2020 through August 31, 2021. We conducted three separate analyses for each of the three COVID-19 vaccines used in the US. Crude non-COVID-19 mortality rates were reported by vaccine type, age, sex, and race/ethnicity. The counting process model for survival analyses was used to analyze non-COVID-19 mortality where a new observation period began when the vaccination status changed upon receipt of the first dose and the second dose. We used calendar time as the basic time scale in survival analyses to implicitly adjust for season and other temporal trend factors. A propensity score approach was used to adjust for the potential imbalance in confounders between the vaccinated and comparison groups. RESULTS: For each vaccine type and across age, sex, and race/ethnicity groups, crude non-COVID-19 mortality rates among COVID-19 vaccinees were lower than those among comparators. After adjusting for confounders with the propensity score approach, the adjusted hazard ratios (aHRs) were 0.46 (95% confidence interval [CI], 0.44-0.49) after dose 1 and 0.48 (95% CI, 0.46-0.50) after dose 2 of the BNT162b2 vaccine, 0.41 (95% CI, 0.39-0.44) after dose 1 and 0.38 (95% CI, 0.37-0.40) after dose 2 of the mRNA-1273 vaccine, and 0.55 (95% CI, 0.51-0.59) after receipt of Ad26.COV2.S. CONCLUSION: While residual confounding bias remained after adjusting for several individual-level and community-level risk factors, no increased risk was found for non-COVID-19 mortality among recipients of three COVID-19 vaccines used in the US.

Investigating Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Congenital Anomalies.

INTRODUCTION: This observational retrospective matched cohort study evaluated the safety of a prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination, Boostrix. We previously reported on the risk of maternal and neonatal outcomes; here we report on the risk of congenital anomalies in infants at birth through 6 months of age. METHODS: The study included pregnant Kaiser Permanente Southern California members. Women who received the Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019 were matched to women who were pregnant between January 2012 and December 2014 and were not vaccinated with Tdap during pregnancy. Unadjusted and adjusted relative risks (aRRs) with 95% confidence intervals were estimated by Poisson regression. Quantitative secular trend analyses, from 2011 to 2017, were conducted on congenital anomalies with a statistically significant aRR > 1. RESULTS: The analysis consisted of 16,350 and 16,088 live-born infants in the Tdap-exposed and unexposed cohorts, respectively. Of the 14 congenital anomaly body systems evaluated, 8 (eye, ear/face/neck, respiratory, upper gastrointestinal, genital, renal, musculoskeletal, integument) had statistically significant elevated aRRs, with point estimates ranging from 1.17 to 2.02. The observed elevated aRRs were consistent with their respective secular increases over time. CONCLUSION: Cautious interpretation of these findings is warranted as these increases may have resulted from improved identification and diagnosis. Furthermore, the biological plausibility of an association between maternal vaccine exposure in the third trimester of pregnancy and birth defects is low. The overall study findings support the safety of maternal immunization with Boostrix during the third trimester of pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03463577.

Kawasaki Disease Following the 13-valent Pneumococcal Conjugate Vaccine and Rotavirus Vaccines.

BACKGROUND: Temporal associations between Kawasaki disease (KD) and childhood vaccines have been reported. Limited data on KD following 13-valent pneumococcal conjugate (PCV13) and rotavirus vaccines are available. METHODS: We conducted a self-controlled risk interval study using Vaccine Safety Datalink electronic health record data to investigate the risk of KD following PCV13 and rotavirus vaccines in children <2 years of age who were born from 2006 to 2017. All hospitalized KD cases identified by International Classification of Diseases diagnosis codes that fell within predefined risk (days 1-28 postvaccination) and control (days 29-56 for doses 1 and 2, and days 43-70 for doses 3 and 4) intervals were confirmed by manual chart review. RESULTS: During the study period, 655 cases of KD were identified by International Classification of Diseases codes. Of these, 97 chart-confirmed cases were within risk or control intervals. In analyses, the age-adjusted relative risk for KD following any dose of PCV13 was 0.75 (95% confidence interval, 0.47-1.21). Similarly, the age-adjusted relative risk for KD following any dose of rotavirus vaccine was 0.66 (95% CI, 0.40-1.09). Overall, there was no evidence of an elevated risk of KD following PCV13 or rotavirus vaccines by dose. In addition, no statistically significant temporal clustering of KD cases was identified during days 1 to 70 postvaccination. CONCLUSIONS: PCV13 and rotavirus vaccination were not associated with an increased risk of KD in children <2 years of age. Our findings provide additional evidence for the overall safety of PCV13 and rotavirus vaccines.