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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.

The COVID-19 pandemic caused an abrupt drop in in-person health care (inpatient, Emergency Department, outpatient) and an increase in telehealth care, which poses challenges in vaccine safety studies that identify outcomes from in-person encounters. We examined the changes in incidence rates of selected encounter-based outcomes during the COVID-19 pandemic.We assembled a cohort of members from 8 Vaccine Safety Datalink sites from January 1, 2017 through December 31, 2020. Using ICD-10 diagnosis codes or laboratory criteria, we identified 21 incident outcomes in traditional in-person settings and all settings. We defined 4 periods in 2020: January-February (pre-pandemic), April-June (early pandemic), July-September (middle pandemic), and October-December (late pandemic). We defined four corresponding periods in each year during 2017-2019. We calculated incidence rates, conducted difference in difference (DiD) analyses, and reported ratios of incidence rate ratios (RRR) to examine changes in rates from pre-pandemic to early, middle, and late pandemic in 2020, after adjusting for changes across similar periods in 2017-2019.Among 10 million members, regardless of setting and after adjusting for changes during 2017-2019, we found that incidence rates of acute disseminated encephalomyelitis, encephalitis/myelitis/encephalomyelitis/meningoencephalitis, and thrombotic thrombocytopenic purpura did not significantly change from the pre-pandemic to early, middle or late pandemic periods (p-values ≥ 0.05). Incidence rates decreased from the pre-pandemic to early pandemic period during 2020 for acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, convulsions/seizures, Guillain-Barré syndrome, immune thrombocytopenia (ITP), narcolepsy/cataplexy, hemorrhagic stroke, ischemic stroke, and venous thromboembolism (p-values 0.05). Incidence rates of Bell's palsy, ITP, and narcolepsy/cataplexy were higher in all settings than in traditional in-person settings during the three pandemic periods (p-values 0.05).Rates of some clinical outcomes during the pandemic changed and should not be used as historical background rates in vaccine safety studies. Inclusion of telehealth visits should be considered for vaccine studies involving Bell's palsy, ITP, and narcolepsy/cataplexy.

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.

Background As prenatal vaccinations continue to be given more frequently, it is important to assess long-term safety events. We investigated the association between prenatal influenza vaccination or infection and autism spectrum disorder (ASD) in offspring. Methods A retrospective cohort study of mother–child pairs with deliveries between 1 January 2011 and 31 December 2014 at Kaiser Permanente Southern California was performed. Children aged >1 year were followed through 31 December 2018. Maternal influenza vaccination or infection during pregnancy was obtained from electronic health records. ASD was defined by International Classification of Diseases, Ninth or Tenth Revisions, Clinical Modification, codes after age 1 year. Cox proportional hazard models estimated the crude and inverse probability of treatment weighted (IPTW) hazard ratios (HR) for the association between maternal influenza vaccination or infection and ASD. Results There were 84 739 mother–child pairs included in the final analytic sample. Of the 46 257 women vaccinated, 32.4% were vaccinated during the first trimester, 41.8% during the second trimester, and 25.8% during the third trimester. ASD was diagnosed in 1930 (2.3%) children. The IPTW analyses showed no association between prenatal influenza vaccination or infection and ASD in offspring (HR, 1.04; 95% confidence interval [CI], .95–1.13; HR, 1.12; 95% CI, .66–1.89, respectively). Conclusions Prenatal influenza vaccination or infection was not associated with ASD risk in offspring. The findings support recommendations to vaccinate pregnant women to protect themselves and their infants, both of whom are vulnerable to severe morbidity following infection.

BACKGROUND mRNA COVID-19 vaccines were initially authorized as a 2-dose primary series and have been widely used in the US. Understanding risk factors for not completing the 2-dose primary series is critical to evaluate COVID-19 vaccination programs and to promote completion of the 2-dose primary series. OBJECTIVE The aim of this study was to examine potential risk factors for not completing a 2-dose primary series of mRNA COVID-19 vaccination. METHODS We conducted a retrospective cohort study among members aged ≥18 years from a large integrated health care system, Kaiser Permanente Southern California, during 12/14/2020-06/30/2022. Non-completion of the 2-dose primary series was defined as not completing the second dose within 6 months after receipt of the first dose. A logistic regression model was fit to examine associations of individual-level and community-level risk factors with non-completion of the 2-dose primary series. RESULTS Among 2.5 million recipients of ≥1 dose of mRNA COVID-19 vaccines, only 3.3% did not complete the second dose within 6 months. Members aged 25-44 years, 65-74 years, and ≥75 years were less likely to not complete the 2-dose primary series than those aged 18-24 years while members aged 45-64 years were more likely to not complete the 2-dose primary series (adjusted odds ratio (aOR)=1.14 [95% CI, 1.11−1.17]). Male sex was associated with higher odds of non-completion (aOR=1.19 [95% CI, 1.18−1.21]. Hispanic and non-Hispanic Black race/ethnicities were associated with lower odds of non-completion (range of aOR 0.75−0.90). Having Medicaid and prior influenza vaccination were associated with higher odds of non-completion. Having SARS-CoV-2 infection, experiencing an adverse event (AEs), or having an inpatient/emergency department (ED) visit during the minimum recommended dose intervals were associated with higher odds of not completing the 2-dose primary series (aOR=2.33, 2.21, and 2.05, respectively). Those who received the first dose before June 30, 2021 were more likely to complete the 2-dose primary series within 6 months of receipt of the first dose. CONCLUSIONS Male, Medicaid coverage, and SARS-CoV-2 infection, AEs, and inpatient and ED visits during the minimum recommended dose intervals were significantly associated with non-completion of the 2-dose primary series while older age≥65 and Black and Hispanic race/ethnicity were associated with higher completion rate.

Background While a 3-dose mRNA-1273 primary series is recommended for moderately or severely immunocompromised (IC) individuals in the U.S., some IC individuals do not complete the 3-dose series. We conducted a matched cohort study to evaluate the relative vaccine effectiveness (rVE) of the 3-dose mRNA-1273 primary series vs. 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 disease in IC individuals. Methods IC individuals aged ≥18 years with ≥12 months of Kaiser Permanente Southern California membership who received 3 doses of mRNA-1273 ≥24 days apart were 1:1 matched with randomly selected IC 2-dose recipients on age, sex, race/ethnicity, and 2nd dose date. Third doses were accrued from 08/12/2021 to 12/31/2021, with follow-up through 1/31/2022, spanning the delta and omicron periods. Outcomes were SARS-CoV-2 infection (positive molecular test or diagnosis code), COVID-19 hospitalization, and COVID-19 hospital death. Adjusted hazard ratios (aHR) with confidence intervals (CI) were estimated by Cox proportional hazards models. Adjusted rVE (%) was calculated as (1-aHR) x 100. Results Our study included 21,942 3-dose and 21,942 2-dose mRNA-1273 IC recipients. Adjusted rVE of 3 doses compared to 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 (Table 1). Adjusted rVE against SARS-CoV-2 infection ranged from 43.0% to 59.1% across subgroups of age, sex, race/ethnicity, history of SARS-CoV-2 infection, pregnancy, and comorbidities (Table 2). Point estimates of the 3-dose rVE were higher against COVID-19 infection and hospitalization in the first 3 months, compared to 3–6 months after the 3rd dose (Table 3). Conclusion Three doses of mRNA-1273 provide additional protection against SARS-CoV-2 infection and severe outcomes for IC individuals, compared to 2 doses, highlighting the importance of completing 3-doses for IC populations. However, possible waning of protection against SARS-CoV-2 infection and severe outcomes after 3 months supports the ACIP recommendation of a booster dose at least 3 months after the 3rd primary series dose for adequate protection of IC individuals. Disclosures Jennifer H. Ku, PhD MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support Lina S. Sy, MPH, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Seqirus: Grant/Research Support Lei Qian, PhD, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Bradley Ackerson, MD, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Yi Luo, PhD, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Julia Tubert, MPH, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Gina Lee, MPH, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Ana Florea, PhD MPH, Gilead: Grant/Research Support|GSK: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Carla Talarico, PhD, Moderna: Employee of and a shareholder in Moderna Inc. Sijia Qiu, MS, Dynavax: Grant/Research Support|Moderna: Grant/Research Support Yun Tian, MS, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Hung Fu Tseng, PhD MPH, GSK: Grant/Research Support|Janssen: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Seqirus: Grant/Research Support.

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.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.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.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.

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.

Purpose A pre-licensure clinical trial of a two-dose cytosine phosphoguanine adjuvanted hepatitis B vaccine (HEPLISAV-B® [Dynavax, USA]; HepB-CpG vaccine) found an unanticipated numerical imbalance in acute myocardial infarction (AMI) compared to recipients of a three-dose aluminum adjuvanted hepatitis B vaccine (ENGERIX-B® [GlaxoSmithKline, Belgium]; HepB-alum vaccine). A post-licensure study was required to compare AMI rates among recipients of HepB-CpG vaccine and HepB-alum vaccine. Individuals with diabetes mellitus (DM), who are at higher risk of AMI, comprise more than half of the post-licensure study cohort. To inform the ongoing post-licensure study, we examined the association between AMI and receipt of HepB-alum vaccine in individuals with DM. Methods We conducted a case-control study nested in a cohort of individuals with DM ages ≥40 years at Kaiser Permanente Southern California using electronic health records. AMI cases from 2012 to 2017 were identified by principal discharge diagnosis and matched 1:1 with randomly selected controls. The adjusted odds ratio (aOR) for receipt of ≥1 HepB-alum vaccine dose was compared for AMI cases and controls using conditional logistic regression. We subsequently performed the same matched case-control analysis stratified by year. Results Of 8138 matched case-control pairs, 17.4% of cases and 15.0% of controls received HepB-alum vaccine. The aOR of HepB-alum vaccination comparing cases and controls was 0.97 (95% confidence interval 0.87-1.08). Similarly, there was no significant association between HepB-alum vaccine and AMI in any of the study years. Conclusions HepB-alum vaccination was not associated with AMI in individuals with DM. This finding will provide contextual insight for the ongoing post-licensure study of HepB-CpG vaccine.

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.

Studying the safety of travel vaccines poses challenges since recipients may be traveling during the risk window for adverse events and the identification of a suitable comparison group can also be difficult. The examination of traveler characteristics, travel vaccination patterns, and health care utilization using electronic health record (EHR) data can inform the feasibility of future travel vaccine safety studies.A retrospective cohort study of health plan members in the Vaccine Safety Datalink Project aged 9 months and older who had a travel-related encounter or received a travel vaccine from 2009 to 2018 was performed. Travel regions visited, travel duration, type of travel vaccine received (typhoid, yellow fever, Japanese encephalitis, rabies, and cholera), and timing of vaccination date before departure date were described. Sociodemographic information, clinical characteristics, and health care utilization were compared between travelers who received travel vaccines and travelers who did not.A total of 1,026,822 unique travelers departing from the United States were identified; 612,795 travelers received 898,196 doses of travel vaccines. The most commonly administered travel vaccine was typhoid vaccine and 77% of all travel vaccines were given more than one week prior to departure. Compared with travelers without travel vaccines, travelers with travel vaccines were overall similar but as a group were slightly younger, healthier, and had lower Hispanic representation. Health care utilization dramatically decreased during travel. Outpatient visits decreased from 294.8 visits per 10,000 person-days before travel to 24.2 visits per 10,000 person-days during reported travel dates.Through the EHR information from almost a million travelers, a departure date and duration of travel were successfully captured for the majority of travelers with corresponding health care utilization data. Time after vaccination and prior to departure can potentially be used in the future to compare travelers who receive travel vaccines with travelers who do not receive travel vaccines when looking at adverse events of interest after vaccination.

In 2017, the FDA approved the adjuvanted recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in immunocompetent adults aged 50 years and older. RZV joined zoster vaccine live (ZVL) as U.S.-marketed vaccines against HZ. The Advisory Committee on Immunization Practices preferentially recommended use of RZV over ZVL. In order to inform population-based decision makers (PBDMs) about the incremental clinical and economic impact of RZV adoption, budget impact (BI) models may be used. Populating such models with national data can inform PBDMs about the incremental value of RZV adoption nationally; however, heterogeneity across health plans requires the inclusion of plan-specific data to ensure the relevance of modeling outcomes for plan-specific decision makers.To investigate the clinical and economic outcomes associated with the adoption of RZV in nationally representative populations with commercial and Medicare coverage and to demonstrate the effect of the heterogeneity of health plans using real-world data from a large, integrated delivery network (IDN).We used a publicly available BI model. The model accounts for national and IDN-collected population characteristics (size, age distribution) and epidemiological data (incidence of HZ and complications, HZ recurrence rate), vaccine characteristics from randomized controlled trials and observational studies (efficacy, waning, second dose compliance for RZV, adverse event rate), national costs (vaccine, direct medical for HZ, complications, and vaccine adverse events), and current and anticipated vaccine coverage. We assessed incremental clinical (HZ cases and complications) and economic (per-member-per-month [PMPM] costs) impact at 5-year to 15-year time horizons, comparing scenarios where RZV is solely implemented with one where only ZVL is utilized.Following the adoption of RZV, the incremental HZ cases avoided over 5 and 15 years were estimated to be 1,800 and 15,000 for a commercial plan, 3,800 and 21,000 for a Medicare plan, and 8,600 and 71,000 for a specific IDN. The incremental PMPM budget impact over the same time horizons was estimated to be $0.42 and $0.31, respectively, for a commercial plan, $0.35 and $0.10 for a Medicare plan, and $0.39 and $0.25 for a specific IDN. The differences in results across plans resulted from the population age distribution, the vaccine copay (applied in the Medicare scenario only), the vaccine coverage in the plan, and other plan-specific factors affecting disease epidemiology and costs per case of HZ.Model projections indicated that RZV adoption avoided HZ cases and related complications, with the PMPM budget impact dependent on plan-specific factors. As health gains increased over time, the incremental costs incurred were found to decrease as the shorter-term costs of adopting the new vaccine were increasingly offset by the longer-term benefits of vaccination.GlaxoSmithKline Biologicals SA funded this study (GSK study identifier: HO-17-18378) and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also paid all costs associated with the development and publication of this manuscript. Patterson, Van Oorschot, and Curran are employees of the GSK group of companies and hold shares in the GSK group of companies. Herring, Carrico, and Zhang are employees of RTI Health Solutions, which received funding via a contractual agreement with the GSK group of companies to perform the work contributing to this research. Ackerson, Bruxvoort, Sy, and Tseng are employees of Kaiser Permanente Southern California, which was contracted by the GSK group of companies for the conduct of this study and were members of the KPSC study team. Ackerson, Bruxvoort, Sy, and Tseng report research contracts with the following pharmaceutical companies unrelated to this study: Dynavax (Ackerson, Bruxvoort, and Sy); the GSK group of companies (Ackerson, Bruxvoort, Sy, and Tseng); Novavax (Ackerson, Sy, and Tseng); and Seqirus (Ackerson, Bruxvoort, Sy, and Tseng). Tseng reports having served as a paid consultant for the GSK group of companies. The authors declare no other financial and nonfinancial relationships and activities. Findings from this study were presented at AMCP Nexus 2019; October 29-November 1, 2019; National Harbor, MD.

As prenatal vaccinations become more prevalent, it is important to assess potential safety events. In a retrospective cohort study of Kaiser Permanente Southern California (Pasadena, California) mother-child pairs with birth dates during January 1, 2011–December 31, 2014, we investigated the association between prenatal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Information on Tdap vaccination during pregnancy was obtained from electronic medical records. ADHD was defined by International Classification of Diseases codes (Ninth or Tenth Revision) and dispensed ADHD medication after age 3 years. Children were followed to the date of their first ADHD diagnosis, the end of Kaiser Permanente membership, or the end of follow-up (December 31, 2018). In Cox proportional hazards models, we estimated unadjusted and adjusted hazard ratios for the association between maternal Tdap vaccination and ADHD, with inverse probability of treatment weighting (IPTW) used to adjust for confounding. Of 128,756 eligible mother-child pairs, 85,607 were included in the final sample. The ADHD incidence rate was 3.41 per 1,000 person-years in the Tdap-vaccinated women and 3.93 per 1,000 person-years in the unvaccinated (hazard ratio = 1.01, 95% confidence interval: 0.88, 1.16). The IPTW-adjusted analyses showed no association between prenatal Tdap vaccination and ADHD in offspring (hazard ratio = 1.00, 95% confidence interval: 0.88, 1.14). In this study, prenatal Tdap vaccination was not associated with ADHD risk in offspring, supporting recommendations to vaccinate pregnant women.

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.

The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among pregnant members at Kaiser Permanente Southern California (KPSC). The exposed cohort consisted of women who received Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019. The unexposed cohort consisted of matched women who were pregnant between January 2012 and December 2014 and were not vaccinated with any Tdap vaccine throughout their pregnancy. Maternal and infant characteristics and pre-specified endpoints were collected through automated data and review of the electronic health records. Unadjusted and adjusted relative risks (aRRs) with confidence intervals (CIs) were estimated by Poisson regression. Non-inferiority testing (i.e., to rule out a two-fold increase) was conducted for primary endpoints with adjustment for multiplicity. Superiority testing was conducted without multiplicity adjustment for secondary endpoints. The analysis consisted of 16,606 pairs of Tdap recipients and unexposed pregnant women. For the primary endpoints, the aRR for preeclampsia/eclampsia was 1.38 (98.75% CI:1.21-1.58) and the aRR for intrauterine infection was 1.28 (98.75% CI:1.12-1.47). These increases were consistent with the background increasing trend of these diagnoses among all pregnant women at KPSC since 2011, and the upper limit of the 98.75% CI of both aRRs did not exceed the pre-specified threshold of 2. No increased risks of small for gestational age (aRR = 1.04, 98.75% CI:0.94-1.16) or preterm delivery (aRR = 0.71, 98.75% CI:0.64-0.78) were observed. No evidence of increased risks for secondary endpoints, including poor fetal growth, preterm pre-labor rupture of membranes, stillbirth/fetal death, placental abruption, transfusion during delivery hospitalization, and neonatal death, was observed. Prenatal Tdap vaccination after the 27th week of pregnancy was not associated with increased risks of pre-specified maternal and infant outcomes, supporting the safety of Tdap vaccination during pregnancy.

Background Some vaccines elicit nonspecific immune responses that may protect against heterologous infections. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and coronavirus disease 2019 (COVID-19) outcomes at Kaiser Permanente Southern California. Methods In a cohort design, adults aged ≥50 years who received ≥1 RZV dose before 1 March 2020 were matched 1:2 to unvaccinated individuals and followed until 31 December 2020. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive severe acute respiratory syndrome coronavirus 2 test and controls had only negative tests, during 1 March–31 December 2020. Adjusted odds ratios (aORs) and 95% CIs for RZV receipt were estimated using logistic regression. Results In the cohort design, 149 244 RZV recipients were matched to 298 488 unvaccinated individuals. The aHRs for COVID-19 diagnosis and hospitalization were 0.84 (95% CI, .81–.87) and 0.68 (95% CI, .64–.74), respectively. In the test-negative design, 8.4% of 75 726 test-positive cases and 13.1% of 340 898 test-negative controls had received ≥1 RZV dose (aOR, 0.84 [95% CI, .81–.86]). Conclusions RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization. Further study of vaccine-induced nonspecific immunity for potential attenuation of future pandemics is warranted.

BackgroundVaccines may elicit long-term boosting of innate immune responses that can help protect against COVID-19. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and COVID-19 outcomes at Kaiser Permanente Southern California.MethodsIn a cohort design, adults aged ≥50 years who received ≥1 RZV dose prior to 3/1/2020 were matched 1:2 to unvaccinated individuals and followed until 12/31/2020. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive SARS-CoV-2 test and controls had only negative tests, from 3/1/2020-12/31/2020. Adjusted odds ratios (aOR) and 95% CIs for prior receipt of RZV were estimated using logistic regression.ResultsIn the cohort design, 149,244 RZV recipients were matched to 298,488 unvaccinated individuals. The aHRs (95% CI) for COVID-19 diagnosis and hospitalization were 0.84 (0.81-0.87) and 0.68 (0.64-0.74), respectively. In the test-negative design, 8.4% of 75,726 test-positive cases and 13.1% of 340,898 test-negative controls had received ≥1 RZV dose. The aOR (95% CI) was 0.84 (0.81-0.86).ConclusionRZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization, suggesting RZV elicits heterologous protection, possibly through trained immunity.

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.

Background The 2-dose recombinant zoster vaccine (RZV) series is recommended for prevention of herpes zoster (HZ) in adults aged ≥50 years, but data are limited on the impact of concomitant administration with other vaccines on subsequent HZ risk. Methods This cohort study included Kaiser Permanente Southern California members aged ≥50 years who received 2 doses of RZV 4 weeks to ≤6 months apart during 1 April 2018–30 September 2019. RZV recipients with and without same-day concomitant vaccination for either RZV dose were followed up for incident HZ beginning 31 days after the second RZV dose until 30 September 2020. The hazard ratio (HR) for HZ comparing RZV recipients with and without concomitant vaccination was estimated using Cox proportional hazards regression, adjusting for confounders. Results RZV with and without concomitant vaccination was received by 12 898 and 28 353 individuals, respectively. HZ occurred among 41 individuals with concomitant vaccination (incidence rate, 2.2 [95% confidence interval {CI}, 1.6–3.0] per 1000 person-years) and 136 without concomitant vaccination (3.4 [95% CI, 2.9–4.0] per 1000 person-years). The adjusted HR for HZ comparing RZV recipients with and without concomitant vaccination was 0.75 (95% CI, .53–1.08). Conclusions HZ risk was not significantly different between RZV recipients with and without concomitant vaccination, supporting recommendations allowing for concomitant administration of RZV with other vaccines.

Objective Local reactions are the most common vaccine-related adverse event. There is no specific diagnosis code for local reaction due to vaccination. Previous vaccine safety studies used non-specific diagnosis codes to identify potential local reaction cases and confirmed the cases through manual chart review. In this study, a natural language processing (NLP) algorithm was developed to identify local reaction associated with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in the Vaccine Safety Datalink. Methods Presumptive cases of local reactions were identified among members ≥ 11 years of age using ICD-9-CM codes in all care settings in the 1–6 days following a Tdap vaccination between 2012 and 2014. The clinical notes were searched for signs and symptoms consistent with local reaction. Information on the timing and the location of a sign or symptom was also extracted to help determine whether or not the sign or symptom was vaccine related. Reactions triggered by causes other than Tdap vaccination were excluded. The NLP algorithm was developed at the lead study site and validated on a stratified random sample of 500 patients from five institutions. Results The NLP algorithm achieved an overall weighted sensitivity of 87.9%, specificity of 92.8%, positive predictive value of 82.7%, and negative predictive value of 95.1%. In addition, using data at one site, the NLP algorithm identified 3326 potential Tdap-related local reactions that were not identified through diagnosis codes. Conclusion The NLP algorithm achieved high accuracy, and demonstrated the potential of NLP to reduce the efforts of manual chart review in vaccine safety studies.

Background The Vaccine Safety Datalink (VSD) uses vaccination data from electronic health records (EHR) at eight integrated health systems to monitor vaccine safety. Accurate capture of data from vaccines administered outside of the health system is critical for vaccine safety research, especially for COVID-19 vaccines, where many are administered in non-traditional settings. However, timely access and inclusion of data from Immunization Information Systems (IIS) into VSD safety assessments is not well understood. Methods We surveyed the eight data-contributing VSD sites to assess: 1) status of sending data to IIS; 2) status of receiving data from IIS; and 3) integration of IIS data into the site EHR. Sites reported separately for COVID-19 vaccination to capture any differences in capacity to receive and integrate data on COVID-19 vaccines versus other vaccines. Results All VSD sites send data to and receive data from their state IIS. All eight sites (100%) routinely integrate IIS data for COVID-19 vaccines into VSD research studies. Six sites (75%) also routinely integrate all other vaccination data; two sites integrate data from IIS following a reconciliation process, which can result in delays to integration into VSD datasets. Conclusions COVID-19 vaccines are being administered in a variety of non-traditional settings, where IIS are commonly used as centralized reporting systems. All eight VSD sites receive and integrate COVID-19 vaccine data from IIS, which positions the VSD well for conducting quality assessments of vaccine safety. Efforts to improve the timely receipt of all vaccination data will improve capacity to conduct vaccine safety assessments within the VSD.

Background Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, due to the difficulty of finding SIRVA cases in large health care databases, population-based studies are scarce. Objective The goal of the research was to develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes. Methods We conducted the study among members of a large integrated health care organization who were vaccinated between April 1, 2016, and December 31, 2017, and had subsequent diagnosis codes indicative of shoulder injury. Based on a training data set with a chart review reference standard of 164 cases, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified 3 groups of positive SIRVA cases (definite, probable, and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated cases. We then applied the final automated NLP algorithm to a broader cohort of vaccinated persons with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases. Results In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 cases without SIRVA. In the broader cohort of 53,585 vaccinations, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.5% (278/291), 67.7% (84/124), and 17.3% (9/52), respectively. Conclusions The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation.

BackgroundShoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, there is a lack of population-based studies due to the challenge of identifying SIRVA cases in large health care databases.ObjectiveTo develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes.MethodsWe conducted the study among members of a large integrated health care organization who were vaccinated between 04/1/2016 and 12/31/2017 and had subsequent diagnosis codes indicative of shoulder injury. Based on a training dataset with a chart review reference standard of 164 individuals, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified three groups of positive SIRVA cases (definite, probable and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated individuals. We then applied the final automated NLP algorithm to a broader cohort of vaccinated individuals with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases.ResultsIn the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 individuals without SIRVA. In the broader cohort of 53,585 individuals, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.3%, 67.7% and 18.9%, respectively.ConclusionsThe algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation.

BACKGROUND Dramatic decreases in outpatient visits and sudden increases in telehealth visits were observed during the COVID-19 pandemic, but it was unclear whether these changes differed by patient demographics and socioeconomic status. OBJECTIVE This study aimed to assess the impact of the pandemic on in-person outpatient and telehealth visits (telephone and video) by demographic characteristics and household income in a diverse population. METHODS We calculated weekly rates of outpatient and telehealth visits by age, sex, race/ethnicity, and neighborhood-level median household income among members of Kaiser Permanente Southern California (KPSC) from January 5, 2020, to October 31, 2020, and the corresponding period in 2019. We estimated the percentage change in visit rates during the early pandemic period (March 22 to April 25, 2020) and the late pandemic period (October 4 to October 31, 2020) from the prepandemic period (January 5 to March 7, 2020) in Poisson regression models for each subgroup while adjusting for seasonality using 2019 data. We examined if the changes in visit rates differed by subgroups statistically by comparing their 95% CIs. RESULTS Among 4.56 million KPSC members enrolled in January 2020, 15.0% (n=682,947) were ≥65 years old, 51.5% (n=2,345,020) were female, 39.4% (n=1,795,994) were Hispanic, and 7.7% (n=350,721) lived in an area of median household income CONCLUSIONS The Hispanic group and low-income group had the largest percentage increase in telehealth utilization in response to the COVID-19 pandemic. The use of virtual care potentially mitigated the impact of the pandemic on health care utilization in these vulnerable populations.

OBJECTIVES The impact of the coronavirus disease 2019 pandemic on vaccination coverage, critical to preventing vaccine-preventable diseases, has not been assessed during the reopening period. METHODS Vaccine uptake and vaccination coverage for recommended vaccines and for measles-containing vaccines at milestone ages were assessed in a large cohort of children aged 0 to 18 years in Southern California during January to August 2020 and were compared with those in the same period in 2019. Differences in vaccine uptake and vaccination coverage (recommended vaccines and measles-containing vaccines) in prepandemic (January to March), stay-at-home (April to May), and reopening (June to August) periods in 2020 and 2019 were compared. RESULTS Total and measles-containing vaccine uptake declined markedly in all children during the pandemic period in 2020 compared with 2019, but recovered in children aged 0 to 23 months. Among children aged 2 to 18 years, measles-containing vaccine uptake recovered, but total vaccine uptake remained lower. Vaccination coverage (recommended and measles-containing vaccines) declined and remained reduced among most milestone age cohorts ≤24 months during the pandemic period, whereas recommended vaccination coverage in older children decreased during the reopening period in 2020 compared with 2019. CONCLUSIONS Pediatric vaccine uptake decreased dramatically during the pandemic, resulting in decreased vaccination coverage that persisted or worsened among several age cohorts during the reopening period. Additional strategies, including immunization tracking, reminders, and recall for needed vaccinations, particularly during virtual visits, will be required to increase vaccine uptake and vaccination coverage and reduce the risk of outbreaks of vaccine-preventable diseases.

Background The COVID-19 pandemic has caused an abrupt reduction in the use of in-person health care, accompanied by a corresponding surge in the use of telehealth services. However, the extent and nature of changes in health care utilization during the pandemic may differ by care setting. Knowledge of the impact of the pandemic on health care utilization is important to health care organizations and policy makers. Objective The aims of this study are (1) to evaluate changes in in-person health care utilization and telehealth visits during the COVID-19 pandemic and (2) to assess the difference in changes in health care utilization between the pandemic year 2020 and the prepandemic year 2019. Methods We retrospectively assembled a cohort consisting of members of a large integrated health care organization, who were enrolled between January 6 and November 2, 2019 (prepandemic year), and between January 5 and October 31, 2020 (pandemic year). The rates of visits were calculated weekly for four settings: inpatient, emergency department (ED), outpatient, and telehealth. Using Poisson models, we assessed the impact of the pandemic on health care utilization during the early days of the pandemic and conducted difference-in-deference (DID) analyses to measure the changes in health care utilization, adjusting for the trend of health care utilization in the prepandemic year. Results In the early days of the pandemic, we observed significant reductions in inpatient, ED, and outpatient utilization (by 30.2%, 37.0%, and 80.9%, respectively). By contrast, there was a 4-fold increase in telehealth visits between weeks 8 (February 23) and 12 (March 22) in 2020. DID analyses revealed that after adjusting for prepandemic secular trends, the reductions in inpatient, ED, and outpatient visit rates in the early days of the pandemic were 1.6, 8.9, and 367.2 visits per 100 person-years (P Conclusions In-person health care utilization decreased drastically during the early period of the pandemic, but there was a corresponding increase in telehealth visits during the same period. By end-June 2020, the combined outpatient and telehealth visits had recovered to prepandemic levels.

After SARS-CoV-2 infection, many patients present with persistent symptoms for at least 6 months, collectively termed post-COVID conditions (PCC). However, the impact of PCC on health care utilization has not been well described.To estimate COVID-19-associated excess health care utilization following acute SARS-CoV-2 infection and describe utilization for select PCCs among patients who had positive SARS-CoV-2 test results (including reverse transcription-polymerase chain reaction and antigen tests) compared with control patients whose results were negative.This matched retrospective cohort study included patients of all ages from 8 large integrated health care systems across the United States who completed a SARS-CoV-2 diagnostic test during March 1 to November 1, 2020. Patients were matched on age, sex, race and ethnicity, site, and date of SARS-CoV-2 test and were followed-up for 6 months. Data were analyzed from March 18, 2021, to June 8, 2022.SARS-CoV-2 infection.Ratios of rate ratios (RRRs) for COVID-19-associated health care utilization were calculated with a difference-in-difference analysis using Poisson regression models. RRRs were estimated overall, by health care setting, by select population characteristics, and by 44 PCCs. COVID-19-associated excess health care utilization was estimated by health care setting.The final matched cohort included 127 859 patients with test results positive for SARS-CoV-2 and 127 859 patients with test results negative for SARS-CoV-2. The mean (SD) age of the study population was 41.2 (18.6) years, 68 696 patients in each group (53.7%) were female, and each group included 66 211 Hispanic patients (51.8%), 9122 non-Hispanic Asian patients (7.1%), 7983 non-Hispanic Black patients (6.2%), and 34 326 non-Hispanic White patients (26.9%). Overall, SARS-CoV-2 infection was associated with a 4% increase in health care utilization over 6 months (RRR, 1.04 [95% CI, 1.03-1.05]), predominantly for virtual encounters (RRR, 1.14 [95% CI, 1.12-1.16]), followed by emergency department visits (RRR, 1.08 [95% CI, 1.04-1.12]). COVID-19-associated utilization for 18 PCCs remained elevated 6 months from the acute stage of infection, with the largest increase in COVID-19-associated utilization observed for infectious disease sequelae (RRR, 86.00 [95% CI, 5.07-1458.33]), COVID-19 (RRR, 19.47 [95% CI, 10.47-36.22]), alopecia (RRR, 2.52 [95% CI, 2.17-2.92]), bronchitis (RRR, 1.85 [95% CI, 1.62-2.12]), pulmonary embolism or deep vein thrombosis (RRR, 1.74 [95% CI, 1.36-2.23]), and dyspnea (RRR, 1.73 [95% CI, 1.61-1.86]). In total, COVID-19-associated excess health care utilization amounted to an estimated 27 217 additional medical encounters over 6 months (212.9 [95% CI, 146.5-278.4] visits per 1000 patients).This cohort study documented an excess health care burden of PCC in the 6 months after the acute stage of infection. As health care systems evolve during a highly dynamic and ongoing global pandemic, these data provide valuable evidence to inform long-term strategic resource allocation for patients previously infected with SARS-CoV-2.

Despite national recommendations, influenza vaccination rates during hospitalizations remain low. Inpatient hospitalization for orthopaedic surgery remains a largely missed opportunity for vaccination. To address potential concerns regarding safety, we evaluated whether influenza vaccination during hospitalization for orthopaedic surgery increases evaluations for infection postdischarge because patients and clinicians often cite fear of this potential outcome.This was a retrospective cohort study that was conducted among patients of a large integrated healthcare organization aged ≥6 months who were hospitalized for an orthopaedic surgery (defined by International Classification of Diseases, Ninth Revision procedure codes) between September 1 and March 31 from 2011 to 2014. Using propensity score matching (1:1) to adjust for confounding, we assessed the association between influenza vaccination during an inpatient stay for orthopaedic surgery and rates of readmission, emergency department visits, outpatient visits, fever (temperature ≥38.0°C), and evaluations for infections less than 7 days postdischarge.Overall, 2,395 hospitalizations with inpatient vaccination and 21,708 hospitalizations without inpatient vaccination were identified. Following successful balance of covariates (standardized difference0.1 for all covariates) through 1:1 propensity score matching, we included 2,376 exposed patients and 2,376 unexposed patients in the matched analysis. In adjusted analyses, compared with those who were not vaccinated during hospitalization, those vaccinated during an inpatient stay for orthopaedic surgery had no statistically significant increase in readmission (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.75 to 1.34), emergency department visits (RR = 1.14, 95% CI: 0.93 to 1.41), fever (RR = 1.31, 95% CI: 0.81 to 2.12), or clinical workups for infection (RR = 1.08, 95% CI: 0.98 to 1.18). A marginally increased risk of outpatient visits in the 7 days postdischarge was detected (RR = 1.13, 95% CI: 1.02 to 1.26).There was no evidence of a substantial increased risk of infection-related outcomes associated with influenza vaccination during hospitalization for orthopaedic surgery. Our data support the recommendation of vaccinating orthopaedic surgery patients against influenza perioperatively.

Background Diagnosis codes are inadequate for accurately identifying herpes zoster ophthalmicus (HZO). Manual review of medical records is expensive and time-consuming, resulting in a lack of population-based data on HZO. Methods We conducted a retrospective cohort study, including 87 673 patients aged ≥50 years who had a new HZ diagnosis and associated antiviral prescription between 2010 and 2018. We developed and validated an automated natural language processing (NLP) algorithm to identify HZO with ocular involvement (ocular HZO). We compared the characteristics of NLP-identified ocular HZO, nonocular HZO, and non-HZO cases among HZ patients and identified the factors associated with ocular HZO among HZ patients. Results The NLP algorithm achieved 94.9% sensitivity and 94.2% specificity in identifying ocular HZO cases. Among 87 673 incident HZ cases, the proportion identified as ocular HZO was 9.0% (n = 7853) by NLP and 2.3% (n = 1988) by International Classification of Diseases codes. In adjusted analyses, older age and male sex were associated with an increased risk of ocular HZO; Hispanic and black race/ethnicity each were associated with a lower risk of ocular HZO compared with non-Hispanic white. Conclusions The NLP algorithm achieved high accuracy and can be used in large population-based studies to identify ocular HZO, avoiding labor-intensive chart review. Age, sex, and race were strongly associated with ocular HZO among HZ patients. We should consider these risk factors when planning for zoster vaccination., Herpes zoster ophthalmicus with ocular involvement (ocular HZO) was significantly undercoded. An NLP-based approach can be used with high accuracy to identify ocular HZO automatically. Older adults also have an increased chance of getting ocular HZO among herpes zoster patients.

Background In 2017, a new adjuvanted recombinant zoster vaccine (RZV) was recommended for adults ≥50 years as two-dose series 2–6 months apart. We evaluated two-dose RZV completion and factors associated with completion. Methods The study included Kaiser Permanente Southern California members ≥50 years who received an RZV dose during April-November 2018 and had continuous membership 12 months before to 9 months after the first RZV dose. Completion was defined as receipt of the second dose ≥4 weeks to 9 months after the first dose (allowing 3-month grace period). Characteristics including age, sex, race/ethnicity, Medicaid status, neighborhood level income and education, comorbidities, history of zoster, health care utilization before and after the first dose, receipt of influenza vaccine, vaccination month (supply shortage proxy), concomitant vaccine, medical center, and medically attended reactions, pain, or gout after the first dose were compared between completers and non-completers. Adjusted odds ratios and 95% confidence intervals for factors associated with completion were estimated by multivariable logistic regression. Results Among 31,120 first dose recipients, 67.2% completed the series within 9 months. In adjusted analyses, higher completion was associated with White compared with Black or Hispanic race/ethnicity, higher neighborhood income and education, no chronic pulmonary disease, diabetes, or dementia, more outpatient visits and fewer emergency department visits before or after the first dose, no hospitalizations after the first dose, receipt of influenza vaccine, receipt of the first dose in June-November rather than April-May 2018, and no concomitant vaccine with the first dose. Systemic reactions or pain after the first dose was not associated with completion. Conclusion Completion of RZV series appears suboptimal in the early phase of implementation. Despite similar accessibility in a health care system, completion varied by race/ethnicity, socioeconomic status, health status, and care seeking behavior, suggesting areas to target for improvement.

Background We describe the clinical epidemiology and outcomes among a large cohort of older adults hospitalized with respiratory syncytial virus (RSV) infection in the United States. Methods Hospitalized adults aged ≥60 years who tested positive for RSV between 1 January 2011 and 30 June 2015 were identified from Kaiser Permanente Southern California. Patient-level demographics, comorbidities, clinical presentation, utilization, complications, and mortality were evaluated. Results There were 664 patients hospitalized with RSV (61% female, 64% aged ≥75 years). Baseline chronic diseases were prevalent (all >30%); 66% developed pneumonia, 80% of which were radiographically confirmed. Very severe tachypnea (≥26 breaths/minute) was common (56%); 21% required ventilator support and 18% were admitted to intensive care unit. Mortality during hospitalization was 5.6% overall (4.6% in 60–74 year olds and 6.1% in ≥75 year olds). Cumulative mortality within 1, 3, 6, and 12 months of admission was 8.6%, 12.3%, 17.2%, and 25.8%, respectively. Conclusion RSV infection in hospitalized older adults often manifested as severe, life-threatening lower respiratory tract illness with high rates of pneumonia, requirement for ventilatory support, and short- and long-term mortality. Increased recognition of the substantial RSV disease burden in adults will be important in evaluation and use of urgently needed interventions.

We identified 10 women hospitalized with respiratory syncytial virus infection during pregnancy. Diagnoses included pneumonia/atelectasis (5), respiratory failure (2), and sepsis (2). Six had obstetrical complications during hospitalization, including 1 induced preterm birth. One required intensive care unit admission and mechanical ventilation. Four infants had complications at birth.