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The question of anticoagulant dosing in hospitalized patients with coronavirus disease-2019 (COVID-19) is unresolved, with randomized trials showing mixed results and heterogeneity of treatment effects for in-hospital death.To examine the association between the intensity of anticoagulation and clinical outcomes in hospitalized patients with COVID-19.Retrospective cohort study of patients with COVID-19 and respiratory impairment who were hospitalized between 3/1/2020-12/31/2020 in two Kaiser Permanente regions.We fit propensity score models using categorical regression to estimate the probability of receiving standard prophylactic, intermediate, or full-dose anticoagulation beginning on the day of admission or on the day of first respiratory deterioration. Exposure was defined by the highest dose on the day of admission or within 24 hours after deterioration. The primary outcome was in-hospital death.We included 17,130 patients in the day of admission analysis and 4,924 patients who experienced respiratory deterioration. There were no differences in propensity score-adjusted odds of in-hospital death for patients who received either intermediate (odds ratio [OR]: 1.00, 95% confidence intervals [CI] 0.89-1.12) or full anticoagulation (OR: 1.00, 95% CI: 0.85-1.17) compared with standard prophylaxis beginning on the day of admission. Similarly, there were no differences in in-hospital death for either intermediate (OR: 1.22, 95% CI: 0.82-1.82) or full anticoagulation (OR: 1.50, 95% CI: 0.90-2.51) compared with standard prophylaxis on the day of deterioration.Results of this real-world, comparative effectiveness study showed no differences in in-hospital death among newly admitted or deteriorating patients with COVID-19 who received intermediate-dose or full anticoagulation compared with standard prophylaxis.

Background: There is evidence of disparities in COVID-19 vaccine acceptance among health care providers. The purpose of this study was to examine confidence receiving and recommending COVID-19 vaccines by health care provider type and race/ethnicity. Methods: This mixed methods study involved a cross-sectional survey and qualitative, semi-structured interviews from March to May 2021 among a sample of physicians, advanced practice providers, nurses, and pharmacists. These workers were recruited through voluntary response sampling from an integrated health system in Southern California. The primary dependent variables were (a) confidence in vaccine safety, (b) confidence in vaccine effectiveness, and (c) intent to recommend the vaccine to others. The primary independent variables were health care provider type and race/ethnicity. Findings: A total of 2,948 providers completed the survey. Nurses relative to physicians were 15% less likely to perceive the COVID-19 vaccine to be safe (risk ratio [RR] = 0.85; 95% confidence interval [CI] = 0.83–0.87); 27% less likely to perceive the vaccine to prevent COVID-19 (RR = 0.73; 95% CI = 0.69–0.76); and 11% less likely to recommend the vaccine to others (RR = 0.89; 95% CI = 0.87–0.91). Hispanic/Latinx providers were 10% less likely to perceive the vaccine to prevent COVID-19 (RR = 0.90; 95% CI = 0.83–0.98) relative to White providers. Qualitative themes included: No need for vaccine; distrusting vaccine research and roll-out; caretaking barriers; uncertainty and potential to change one’s mind; framing vaccine decisions around personal beliefs. Conclusions & Application to Practice: Health care workplaces should consider interventions to increase COVID-19 vaccination among their workers, including education and mandatory vaccination policies.

Introduction: There is evidence for relatively lower COVID-19 vaccine uptake among people of color in the United States. The purpose of this study was to investigate associations between race/ethnicity and COVID-19 vaccine uptake among nurses. Methods: Nurses in Southern California ( N = 1183) completed a one-time, web-based survey to assess COVID-19 vaccine perceptions and uptake. Results: In all, 82.8% of respondents ( N = 979) received at least one COVID-19 vaccine dose. Identifying as East Asian was associated with 14% higher odds of COVID-19 vaccine uptake relative to identifying as White (odds ratio [OR] = 1.14/95% confidence interval [CI] = [1.06, 1.24]); identifying as Filipino was associated with 14% higher odds of uptake (OR = 1.14/95% CI = [1.08, 1.20]); and identifying as Hispanic/Latinx was associated with 6% higher odds of uptake (OR = 1.06/95% CI = [1.00, 1.12]). Discussion: Although nurses and people of color have been identified as groups with low levels of COVID-19 vaccine uptake, this study found that nurses of color received the vaccine at higher levels than their White counterparts.

Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.† Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4-7). This study used whole genome sequencing (WGS) data on SARS-CoV-2-positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4-July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2-positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4-May 19, 2021. During April 15-July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4-July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18-44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States.

Background: Understanding the attributes of COVID-19 clinical severity among people living with HIV (PLWH) compared with those in HIV-uninfected patients is critical for risk stratification and treatment strategies. Methods: We conducted a retrospective study at Kaiser Permanente Southern California among PLWH aged 18 years or older. We compared the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization among PLWH and HIV-uninfected adults. A chart review was conducted for PLWH with COVID-19 to examine viral suppression of HIV and most recent CD4+ counts in the year before COVID-19 diagnosis, known exposures to COVID-19, and clinical presentation. Results: Between March 1, 2020, and May 31, 2020, the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization was 551.2, 57.0, and 9.3 per 10,000 PLWH, respectively, compared with 268.4, 34.6, and 5.3 per 10,000 HIV-uninfected individuals, respectively. Among those with COVID-19, the distribution of race/ethnicity, smoking status, and comorbidities was similar in PLWH and HIV-uninfected patients;however, PLWH were mostly men, younger, and less obese than HIV-uninfected individuals. Health care utilization regarding emergency care and hospitalizations in the year before COVID-19-related hospitalization was similar between the groups. Overall, HIV was virologically suppressed in .95% of PLWH with COVID-19, and HIV viral load and CD4+ status did not differ between hospitalized and nonhospitalized patients. Conclusions: In this population of patients with well-controlled HIV infection, the incidence of testing, diagnosis, and hospitalization for COVID-19 was higher in PLWH than that in HIVuninfected patients. [ABSTRACT FROM AUTHOR] Copyright of JAIDS: Journal of Acquired Immune Deficiency Syndromes is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background In the absence of field efficacy studies, estimating the real-world effectiveness of vaccines may consider immunogenicity from randomized controlled clinical trials and real-world adherence. Combining seroprotection rates (SPRs) with regimen completion rates gives an estimate of an effective vaccine protection rate (eVPR), which can be leveraged to evaluate real-world cost-effectiveness by linking it with vaccine costs to estimate the cost-per-protected patient (CPP). Methods This study evaluated eVPR and CPP as estimates of vaccine clinical- and cost-effectiveness of two-dose (HepB-CpG) and three-dose (HepB-Alum) hepatitis B virus (HBV) vaccines in the general adult population and a subpopulation with diabetes mellitus. eVPR was calculated from head-to-head SPR data from phase 3 clinical trials directly comparing HepB-CpG and HepB-Alum vaccine regimens and real-world head-to-head adherence data. CPP was calculated as the average cost of each regimen divided by eVPR. Results Higher eVPR in the adult population was achieved with HepB-CpG (68.0%) versus HepB-Alum (41.6%), reflecting the combination of higher SPR and vaccine regimen completion. The CPP for HepB-CpG ($331.31) was $45.67 (95% CI: $36.66, $55.19) less than HepB-Alum ($377.09). Greater savings were observed among persons with diabetes, with CPP $149.60 (95% CI: $80.29, $195.63) lower with HepB-CpG ($367.57) than HepB-Alum ($517.37). Conclusions Metrics estimating vaccine real-world effectiveness and value may guide informed decisions in vaccine selection. For example, using eVPR and CPP, HepB-CpG represents a more effective, value-advantaged approach than HepB-Alum toward reducing HBV infection.

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.

Health care workers promote COVID-19 vaccination for adolescent patients, and as parents, may influence their own children to get vaccinated. We conducted virtual, semi-structured qualitative interviews with vaccinated health care workers and their adolescent children to explore their decision-making process for COVID-19 vaccination. In total, 21 health care workers (physicians, nurses, and medical staff) and their adolescent children ( N = 17) participated in interviews. The following three themes described parent-adolescent decision-making for COVID-19 vaccination: (1) family anticipation and hesitation about COVID-19 vaccine approval; (2) parents’ or adolescents’ choice: the decision maker for adolescent COVID-19 vaccination; and (3) leveraging one’s vaccination status to encourage others to get vaccinated. Nurses encouraged adolescent autonomy in decisions for COVID-19 vaccination while physicians viewed vaccination as the parent’s decision. Health care workers and their adolescent children used role-modeling to motivate unvaccinated peers and may model their decision-making process for adolescent COVID-19 vaccination with their own children to support their patients’ and parents’ vaccine decisions.

Host adaptive immune responses may protect against infection or disease when a pathogen is repeatedly encountered. The hazard ratio of infection or disease, given previous infection, is typically sought to estimate the strength of protective immunity. However, variation in individual exposure or susceptibility to infection may introduce frailty bias, whereby a tendency for infections to recur among individuals with greater risk confounds the causal association between previous infection and susceptibility. We introduce a self-matched "case-only" inference method to control for unmeasured individual heterogeneity, making use of negative-control endpoints not attributable to the pathogen of interest. To control for confounding, this method compares event times for endpoints due to the pathogen of interest and negative-control endpoints during counterfactual risk periods, defined according to individuals' infection history. We derive a standard Mantel-Haenszel (matched) odds ratio conveying the effect of prior infection on time to recurrence. We compare performance of this approach to several proportional hazards modeling frameworks and estimate statistical power of the proposed strategy under various conditions. In an example application, we use the proposed method to reestimate naturally acquired protection against rotavirus gastroenteritis using data from previously published cohort studies. This self-matched negative-control design may present a flexible alternative to existing approaches for analyzing naturally acquired immunity, as well as other exposures affecting the distribution of recurrent event times.

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.

A web-based survey was widely distributed between November 1

Objective The coronavirus disease 2019 (COVID-19) pandemic has created a need for data regarding the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women. After implementing universal screening for COVID-19 in women admitted for delivery, we sought to describe the characteristics of COVID-19 in this large cohort of women. Study Design An observational study of women admitted to labor and delivery units in Kaiser Permanente Southern California (KPSC) hospitals between April 6 and May 11, 2020 who were universally offered testing for SARS-CoV-2 infection ( n = 3,963). Hospital inpatient and outpatient physician encounter, and laboratory records were used to ascertain universal testing levels, test results, and medical and obstetrical histories. The prevalence of SARS-CoV-2 infection was estimated from the number of women who tested positive during labor per 100 women delivered. Results Of women delivered during the study period, 3,923 (99.0%) underwent SARS-CoV-2 testing. A total of 17 (0.43%; 95% confidence interval: 0.23–0.63%) women tested positive, and none of them were symptomatic on admission. There was no difference in terms of characteristics between SARS-CoV-2 positive and negative tested women. One woman developed a headache attributed to COVID-19 3 days postpartum. No neonates had a positive test at 24 hours of life. Conclusion The findings suggest that in pregnant women admitted for delivery between April 6 and May 11, 2020 in this large integrated health care system in Southern California, prevalence of SARS-CoV-2 test positive was very low and all patients were asymptomatic on admission. Key Points The prevalence of SARS-CoV-2 infection in a large diverse cohort of term pregnant women was 0.43%. 99% of women accepted SARS-CoV-2 screening on admission to labor and delivery. All women with positive test results were asymptomatic at the time of testing.

Background There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. Methods Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007–2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. Results Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of Conclusions In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children Trial registration Reported in individual primary studies.

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.

Purpose The purpose of this study was to investigate associations between parent vaccine confidence and intention to have their child with autism vaccinated against COVID-19. Design and methods A cross-sectional, web-based survey was conducted from May to July 2021 with parents of children with autism spectrum disorder (N = 322) who were members of an integrated healthcare system in Southern California. Results Approximately 35% of parents intended to vaccinate their child against COVID-19. In adjusted models, positive vaccine beliefs—but not belief in vaccine harm, healthcare provider trust, or parent vaccination status—were associated with intention to vaccinate. Conclusions Though parents usually trust recommendations from pediatric healthcare providers to make decisions about their child's health, these findings suggest that relying on trusted relationships alone may not be sufficient when discussing COVID-19 vaccines and that additional education to bolster vaccine confidence may be needed. Practice implications Pediatric healthcare providers should reinforce the benefits of vaccines for parents who are undecided about COVID-19 vaccines for their children and provide education and evidence-based recommendations to parents who hold erroneous vaccine beliefs about risks, benefits, and current evidence, especially those related to autism.

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 Information and opinions shared by health care providers can affect patient vaccination decisions, but little is known about who health care providers themselves trust for information in the context of new COVID-19 vaccines. OBJECTIVE The purpose of this study is to investigate which sources of information about COVID-19 vaccines are trusted by health care providers and how they communicate this information to patients. METHODS This mixed methods study involved a one-time, web-based survey of health care providers and qualitative interviews with a subset of survey respondents. Health care providers (physicians, advanced practice providers, pharmacists, nurses) were recruited from an integrated health system in Southern California using voluntary response sampling, with follow-up interviews with providers who either accepted or declined a COVID-19 vaccine. The outcome was the type of information sources that respondents reported trusting for information about COVID-19 vaccines. Bivariate tests were used to compare trusted information sources by provider type; thematic analysis was used to explore perspectives about vaccine information and communicating with patients about vaccines. RESULTS The survey was completed by 2948 providers, of whom 91% (n=2683) responded that they had received ≥1 dose of a COVID-19 vaccine. The most frequently trusted source of COVID-19 vaccine information was government agencies (n=2513, 84.2%); the least frequently trusted source was social media (n=691, 9.5%). More physicians trusted government agencies (n=1226, 93%) than nurses (n=927, 78%) or pharmacists (n=203, 78%; PP=.002). Qualitative themes (n=32 participants) about trusted sources of COVID-19 vaccine information were identified: processing new COVID-19 information in a health care work context likened to a “war zone” during the pandemic and communicating information to patients. Some providers were hesitant to recommend vaccines to pregnant people and groups they perceived to be at low risk for COVID-19. CONCLUSIONS Physicians have stronger trust in government sources and their employers for information about COVID-19 vaccines compared with nurses, pharmacists, and advanced practice providers. Strategies such as role modeling, tailored messaging, or talking points with standard language may help providers to communicate accurate COVID-19 vaccine information to patients, and these strategies may also be used with providers with lower levels of trust in reputable information sources.

Objectives To estimate the burden and severity of suspected reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods A retrospective cohort of members of Kaiser Permanente Southern California with PCR-positive SARS-CoV-2 infection between 1st March 2020 and 31st October 2020 was followed through electronic health records for subsequent positive SARS-CoV-2 tests (suspected reinfection) ≥90 days after initial infection, through 31st January 2021. Incidence of suspected reinfection was estimated using the Kaplan–Meier method. Cox proportional hazards models estimated the association of suspected reinfection with demographic and clinical characteristics, hospitalization, and date of initial infection. Results The cohort of 75 149 was predominantly Hispanic (49 648/75 149, 66.1%) and included slightly more females than males (39 736, 52.9%), with few immunocompromised patients (953, 1.3%); 315 suspected reinfections were identified, with a cumulative incidence at 270 days of 0.8% (95% confidence interval (CI) 0.7–1.0%). Hospitalization was more common at suspected reinfection (36/315, 11.4%) than initial infection (4094/75 149, 5.4%). Suspected reinfection rates were higher in females (1.0%, CI 0.8–1.2% versus 0.7%, CI 0.5–0.9%, p 0.002) and immunocompromised patients (2.1%, CI 1.0–4.2% versus 0.8%, CI 0.7–1.0%, p 0.004), and lower in children than adults (0.2%, CI 0.1–0.4% versus 0.9%, CI 0.7–1.0%, p 0.023). Patients hospitalized at initial infection were more likely to have suspected reinfection (1.2%, CI 0.6–1.7% versus 0.8%, CI 0.7–1.0%, p 0.030), as were those with initial infections later in 2020 (150-day incidence 0.4%, CI 0.2–0.5% September–October versus 0.2%, CI 0.1–0.3% March–May and 0.3%, CI 0.2–0.3% June–August, p 0.008). In an adjusted Cox proportional hazards model, being female (hazard ratio (HR) 1.44, CI 1.14–1.81), adult (age 18–39, HR 2.71, CI 1.38–5.31, age 40–59 HR 2.22, CI 1.12–4.41, age ≥60 HR 2.52, CI 1.23–5.17 versus

ImportanceIn 2014, the US Advisory Committee on Immunization Practices (ACIP) extended existing pneumococcal vaccination recommendations for adults aged ≥65 years to include 13-valent pneumococcal conjugate vaccine (PCV13), primarily to prevent non-bacteremic pneumonia.ObjectiveTo determine PCV13 effectiveness against all-cause inpatient plus outpatient medically-attended lower-respiratory tract infection (LRTI) and pneumonia among US older adults.DesignProspective, open cohort study following participants from 2016 to 2019. We conducted analyses in a self-matched framework, comparing outcomes during participants’ follow-up periods before and after receipt of PCV13.SettingKaiser Permanente Southern California (KPSC) integrated healthcare delivery system.ParticipantsAdults aged ≥65 years who received PCV13 between 2016-2019.ExposuresReceipt of PCV13 at ages ≥65 years, concordant with ACIP guidelines.Main outcomes and measuresWe estimated the adjusted hazards ratio (aHR) for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. We computed aHR estimates using Cox proportional hazards models. We defined vaccine effectiveness (VE) as (1–aHR)×100%. We also estimated PCV13-attributable absolute reductions in incidence of LRTI and pneumonia.ResultsObservations were available both before and after PCV13 receipt for 42,700 participants. Among these individuals, 1,419 experienced LRTI and 969 experienced pneumonia over approximately 26,000 combined years of follow-up before PCV13 receipt; 3,849 experienced LRTI and 2,727 experienced pneumonia over approximately 74,000 combined years of follow-up after PCV13 receipt. In adjusted analyses, VE was 9.5% (95% confidence interval: 2.2% to 16.3%) against all-cause medically-attended LRTI and 8.8% (–0.2% to 17.0%) against all-cause medically-attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of 23-valent pneumococcal polysaccharide vaccine. We estimated that PCV13 prevented 0.7 (0.2 to 1.4) and 0.5 (0.0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually. Over a five-year time horizon, one case of LRTI and pneumonia, respectively, was prevented for every 27 (14 to 116) and 42 (–97 to 268) individuals receiving PCV13.Conclusions and relevancePCV13 vaccination among older adults reduced the burden of medically-attended respiratory illness in this population.KEY POINTSQuestionDoes 13-valent pneumococcal vaccine (PCV13) reduce the burden of lower respiratory-tract infection (LRTI) and pneumonia among older adults?FindingsIn this longitudinal cohort study of adults aged 65 years and older from 2016-2019, PCV13 reduced incidence of LRTI and pneumonia episodes due to any cause by 9.5% and 8.8%, respectively. This effect corresponded to prevention of 0.7 and 0.5 episodes of LRTI and pneumonia, respectively, per 100 vaccinated persons each year. Protection from 23-valent pneumococcal polysaccharide vaccine was not apparent.MeaningAmong older adults, PCV13 vaccine administration substantially reduces the burden of medically-attended LRTI and pneumonia.

Background Urinary tract infection (UTI) accounts for a substantial portion of outpatient visits and antibiotic prescriptions in the United States. Few studies have considered sociodemographic factors including low socioeconomic status (SES)—which may increase residential crowding, inappropriate antibiotic prescribing, or comorbidities—as UTI or multidrug-resistant (MDR) UTI risk factors. Methods We used 2015–2017 electronic health record data from 2 California health care systems to assess whether 3 sociodemographic factors—use of Medicaid, use of an interpreter, and census tract–level deprivation—were associated with overall UTI or MDR UTI. UTIs resistant to ≥3 antibiotic classes were considered MDR. Results Analyses included 601 352 UTI cases, 1 303 455 controls, and 424 977 urinary Escherichia coli isolates from Kaiser Permanente Southern California (KPSC) and Sutter Health in Northern California. The MDR prevalence was 10.4% at KPSC and 12.8% at Sutter Health. All 3 sociodemographic factors (ie, use of Medicaid, using an interpreter, and community deprivation) were associated increased risk of MDR UTI. For example, using an interpreter was associated with a 36% (relative risk [RR], 1.36; 95% CI, 1.31 to 1.40) and 28% (RR, 1.28; 95% CI, 1.22 to 1.34) increased risk of MDR UTI at KPSC and Sutter Health, respectively, adjusted for SES and other potential confounding variables. The 3 sociodemographic factors were only weakly associated with UTI overall. Conclusions We found low SES and use of an interpreter to be novel risk factors for MDR UTI in the United States.

Background Urinary tract infections (UTIs) occur commonly, but recent data on UTI rates are scarce. It is unknown how the growth of virtual healthcare delivery affects outpatient UTI management and trends in the United States. Methods From 1 January 2008 to 31 December 2017, UTIs from outpatient settings (office, emergency, and virtual visits) were identified from electronic health records at Kaiser Permanente Southern California using multiple UTI definitions. Annual rates estimated by Poisson regression were stratified by sex, care setting, age, and race/ethnicity. Annual trends were estimated by linear or piecewise Poisson regression. Results UTIs occurred in 1 065 955 individuals. Rates per 1000 person-years were 53.7 (95% confidence interval [CI], 50.6–57.0) by diagnosis code with antibiotic and 25.8 (95% CI, 24.7–26.9) by positive culture. Compared to office and emergency visits, UTIs were increasingly diagnosed in virtual visits, where rates by diagnosis code with antibiotic increased annually by 21.2% (95% CI, 16.5%–26.2%) in females and 29.3% (95% CI, 23.7%–35.3%) in males. Only 32% of virtual care diagnoses had a culture order. Overall, UTI rates were highest and increased the most in older adults. Rates were also higher in Hispanic and white females and black and white males. Conclusions Outpatient UTI rates increased from 2008 to 2017, especially in virtual care and among older adults. Virtual care is important for expanding access to health services, but strategies are needed in all outpatient care settings to ensure accurate UTI diagnosis and reduce inappropriate antibiotic treatment.

Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death. To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018. In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017. The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870). Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season. Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively). Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF.

BACKGROUND: Provider-collected nasopharyngeal specimens for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing are the standard of care in many clinical settings, but patient-collected saliva and anterior nares specimens are less invasive and more flexible alternatives. Prior studies comparing specimen types for SARS-CoV-2 molecular testing have been limited by small sample sizes and low pretest probability. We conducted a large observational study among symptomatic adults at 7 emergency departments of Kaiser Permanente Southern California to examine sensitivity of SARS-CoV-2 molecular tests by specimen type and patient characteristics. METHODS: Provider-collected nasopharyngeal/oropharyngeal (NP/OP) specimens and patient-collected saliva and anterior nares specimens were collected at the same visit and analyzed with the Roche cobas® SARS-CoV-2 assay. Patients were considered truly positive for SARS-CoV-2 if any of the three specimens was positive and negative if all three specimens were negative. Factors associated with discordant and missed positive results were examined with multivariable logistic regression. RESULTS: Of 2112 patients, 350 (16.6%) were positive for SARS-CoV-2. Sensitivity of NP/OP was 93.7% (95% confidence interval [CI] 90.6%-96.0%), sensitivity of saliva was 87.7% (83.8%-91.0%), and sensitivity of anterior nares was 85.4% (81.3%-89.0%). Patients ages 18-39 years versus ≥40 years were more likely to have discordant results [adjusted odds ratio (aOR) 1.97 (1.12-3.45)], as were patients with

Background While secondary pneumococcal pneumonia occurs less commonly after coronavirus disease 2019 (COVID-19) than after other viral infections, it remains unclear whether other interactions occur between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae. Methods We probed potential interactions between these pathogens among adults aged ≥65 years by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]). We estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models with doubly robust inverse-propensity weighting. We assessed effect modification by antibiotic exposure to further test the biologic plausibility of a causal role for pneumococci. Results Among 531 033 adults, there were 3677 COVID-19 diagnoses, leading to 1075 hospitalizations and 334 fatalities, between 1 March and 22 July 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval [CI], .59–.72), 0.68 (95% CI, .57–.83), and 0.68 (95% CI, .49–.95), respectively. Prior PPSV23 receipt was not associated with protection against the 3 outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (95% CI, .50–.84) and 0.62 (95% CI, .56–.70) during the risk periods 91–365 days and >365 days, respectively, following antibiotic receipt. Conclusions Reduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests that pneumococci may interact with SARS-CoV-2.

IMPORTANCE: The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study. OBJECTIVE: To compare the rate of acute MI between recipients of HepB-CpG vaccine and HepB-alum vaccine. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort noninferiority study was conducted at Kaiser Permanente Southern California (KPSC), an integrated health care system with 15 medical centers and approximately 4.7 million members. The study included 69 625 adults not undergoing dialysis who received at least 1 dose of a hepatitis B vaccine in either family medicine or internal medicine departments at KPSC from August 7, 2018, to October 31, 2019 (November 30, 2020, final follow-up). EXPOSURES: Receipt of HepB-CpG vaccine vs HepB-alum vaccine. The first dose during the study period was the index dose. MAIN OUTCOMES AND MEASURES: Individuals were followed up for 13 months after the index dose for occurrence of type 1 acute MI. Potential events were identified using diagnosis codes and adjudicated by cardiologists. The adjusted hazard ratio (HR) of acute MI was estimated comparing recipients of HepB-CpG vaccine with recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics. The upper limit of the 1-sided 97.5% CI was compared with a noninferiority margin of 2. RESULTS: Of the 31 183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n = 15 965) were men, and 52.7% (n = 16 423) were Hispanic. Of the 38 442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19 533) were men, and 47.1% (n = 18 125) were Hispanic. Characteristics were well-balanced between vaccine groups after IPTW. Fifty-two type 1 acute MI events were confirmed among recipients of HepB-CpG vaccine for a rate of 1.67 per 1000-person-years, and 71 type 1 acute MI events were confirmed among recipients of HepB-alum vaccine for a rate of 1.86 per 1000 person-years (absolute rate difference, −0.19 [95% CI, −0.82 to 0.44]; adjusted HR, 0.92 [1-sided 97.5% CI, ∞ to 1.32], which was below the noninferiority margin; P

Background: Vaccinations prevent respiratory infections in heart failure (HF) patients, leading to less HF decompensation. Given a growing interest around influenza vaccination and mortality reduction, we examined the association between influenza vaccination and all-cause mortality among members with HF in Kaiser Permanente Southern California. Methods: We identified members with HF by ICD-9/10 diagnosis codes prior to September 1 each year from 2009-2017. The first flu vaccination in each season (September 1-May 31) was recorded. Vaccinated/unvaccinated members were matched 1:1 on age, sex, and ejection fraction. Matched pairs were followed from the vaccinated member’s vaccination date through the end of the season for mortality, with the last date of follow-up on May 31, 2018. Frequency of healthcare utilization in the year before each season was compared between vaccinated and unvaccinated members. We calculated unadjusted and utilization-adjusted rate ratios (RR) and 95% confidence intervals (CI) for the association between vaccination and mortality. Results: Between 2009-2018, influenza vaccination among HF members increased from 74.8% to 80.3% and the number of vaccinated and unvaccinated matched pairs increased to 4,451 through the 2017-2018 season. The proportions of vaccinated and unvaccinated members with ≥ 1 prior inpatient visit and ≥1 prior emergency department (ED) visit were similar (46.2% vs 44.6% and 34.3% vs 32.6%, respectively). More unvaccinated than vaccinated members had ≥ 5 outpatient visits (41.9% vs 28.1%). After adjustment for inpatient, outpatient and ED visits, vaccinated members had between a 16% and 36% lower mortality rate across all seasons (RR 0.64 [95% CI 0.55, 0.75] in 2013-2014 and RR 0.84 [95% CI 0.73, 0.96] in 2017-2018). (Table) Conclusion: Influenza vaccination was likely associated with a lower mortality rate among HF patients. Future work will examine the potential confounding by comorbidities and treatments.

BACKGROUND Successful linkage to preexposure prophylaxis (PrEP) and retention in care are important for HIV prevention. We examined gaps in PrEP care following referral and factors associated with PrEP linkage and persistence in an integrated health care system in the United States. METHODS We identified individuals referred for PrEP from 2014 to 2017 at the Kaiser Permanente Southern California using electronic health records and assessed linkage to care, PrEP prescription orders and fills, and PrEP persistence (medication possession ratio ≥80%) in the year after the first fill. We evaluated demographic and clinical factors potentially associated with PrEP linkage and persistence using a series of multivariable modified Poisson regression models. RESULTS Of 2995 referred individuals, 74.9% were linked to PrEP care. Nearly all those linked to care were prescribed PrEP and filled a prescription, but only 47.4% of those who filled a prescription were persistent on PrEP. Individuals aged

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.

Host adaptive immune responses may protect against infection or disease when a pathogen is repeatedly encountered. The hazard ratio of infection or disease, given previous infection, is typically sought to estimate the strength of protective immunity. However, variation in individual exposure or susceptibility to infection may introduce frailty bias, whereby a tendency for infections to recur among individuals with greater risk confounds the causal association between previous infection and susceptibility. We introduce a self-matched “case-only” inference method to control for unmeasured individual heterogeneity, making use of negative-control endpoints not attributable to the pathogen of interest. To control for confounding, this method compares event times for endpoints due to the pathogen of interest and negative-control endpoints during counterfactual risk periods, defined according to individuals’ infection history. We derive a standard Mantel-Haenszel (matched) odds ratio conveying the effect of prior infection on time to recurrence. We compare performance of this approach to several proportional hazards modeling frameworks, and estimate statistical power of the proposed strategy under various conditions. In an example application, we use the proposed method to re-estimate naturally-acquired protection against rotavirus gastroenteritis using data from previously-published cohort studies. This self-matched negative-control design may present a flexible alternative to existing approaches for analyzing naturally-acquired immunity, as well as other exposures affecting the distribution of recurrent event times.