Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals.

Importance: Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. Objective: To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. Design, Setting, and Participants: This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Exposures: Self-reported or electronic health record (EHR)-derived race, ethnicity, and preferred language. Main Outcomes and Measures: Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. Results: There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; χ21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ21 = 22.8; P = .002). Conclusions and Relevance: Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.

Influenza vaccination accuracy among adults: Self-report compared with electronic health record data.

OBJECTIVE: To assess the validity of electronic health record (EHR)-based influenza vaccination data among adults in a multistate network. METHODS: Following the 2018-2019 and 2019-2020 influenza seasons, surveys were conducted among a random sample of adults who did or did not appear influenza-vaccinated (per EHR data) during the influenza season. Participants were asked to report their influenza vaccination status; self-report was treated as the criterion standard. Results were combined across survey years. RESULTS: Survey response rate was 44.7% (777 of 1740) for the 2018-2019 influenza season and 40.5% (505 of 1246) for the 2019-2020 influenza season. The sensitivity of EHR-based influenza vaccination data was 75.0% (95% confidence interval [CI] 68.1, 81.1), specificity 98.4% (95% CI 92.9, 99.9), and negative predictive value 73.9% (95% CI 68.0, 79.3). CONCLUSIONS: In a multistate research network across two recent influenza seasons, there was moderate concordance between EHR-based vaccination data and self-report.

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

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

Latent tuberculosis infection testing practices in a large U.S. integrated healthcare system.

PURPOSE: Tuberculosis (TB) is a public health threat with >80% of active TB in the U.S. occurring due to reactivation of latent tuberculosis infection (LTBI). We may be under-screening those with high risk for LTBI and over-testing those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. METHODS: This study, conducted between 01/01/2008 and 12/31/2019 at Kaiser Permanente Southern California, included individuals ≥18 years of age without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. RESULTS: Among 3,816,884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [S.D. 16.1]), 706,367 (19%) were tested for LTBI, among whom 60,393 (9%) had ≥1 positive result. Among 1,211,971 individuals meeting ≥1 screening criteria for LTBI, 210,025 (17%) were tested for LTBI. Factors associated with higher adjusted odds (aOR) of testing positive included male sex [aOR: 1.32, 95% CI:1.30-1.35], Asian/Pacific Islander [2.78, 2.68-2.88], current smoking [1.24, 1.20-1.28], diabetes [1.13, 1.09-1.16], hepatitis B [1.45, 1.34-1.57], hepatitis C [1.54, 1.44-1.66], and birth in a country with an elevated TB rate [3.40, 3.31-3.49]). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. CONCLUSIONS: Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States: The contribution of vaccine-related attitudes.

OBJECTIVE: Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States have been documented. This study assessed the contribution of vaccine-related attitudes to coverage disparities. METHODS: Surveys were conducted following the 2019-2020 and 2020-2021 influenza seasons in a US research network. Using electronic health record data to identify pregnant women, random samples were selected for surveying; non-Hispanic Black women and influenza-unvaccinated women were oversampled. Regression-based decomposition analyses were used to assess the contribution of vaccine-related attitudes to racial and ethnic differences in influenza vaccination. Data were combined across survey years, and analyses were weighted and accounted for survey design. RESULTS: Survey response rate was 41.2% (721 of 1748) for 2019-2020 and 39.3% (706 of 1798) for 2020-2021. Self-reported influenza vaccination was higher among non-Hispanic White respondents (79.4% coverage, 95% CI 73.1%-85.7%) than Hispanic (66.2% coverage, 95% CI 52.5%-79.9%) and non-Hispanic Black (55.8% coverage, 95% CI 50.2%-61.4%) respondents. For all racial and ethnic groups, a high proportion (generally >80%) reported being seen for care, recommended for influenza vaccination, and offered vaccination. In decomposition analyses, vaccine-related attitudes (e.g., worry about vaccination causing influenza; concern about vaccine safety and effectiveness) explained a statistically significant portion of the observed racial and ethnic disparities in vaccination. Maternal age, education, and health status were not significant contributors after controlling for vaccine-related attitudes. CONCLUSIONS: In a setting with relatively high influenza vaccination coverage among pregnant women, racial and ethnic disparities in coverage were identified. Vaccine-related attitudes were associated with the disparities observed.

Prior Screening for Latent Tuberculosis Among Patients Diagnosed With Tuberculosis Disease: Missed Opportunities?

Background: California has the largest number of tuberculosis (TB) disease cases in the United States. This study in a large California health system assessed missed opportunities for latent tuberculosis (LTBI) screening among patients with TB disease. Methods: Kaiser Permanente Southern California patients who were ≥18 years old with membership for ≥24 months during the study period from 1 January 2008 to 31 December 2019 were included. Prior LTBI test (tuberculin skin test or interferon-γ release assay) or diagnosis code prior to TB disease diagnosis was assessed among patients with observed TB disease (confirmed by polymerase chain reaction and/or culture). In the absence of current treatment practices, more patients screened for LTBI may have developed TB disease. We estimated hypothetical TB disease cases prevented by multiplying LTBI progression rates by the number of LTBI-positive patients prescribed treatment. Results: A total of 1289 patients with observed TB disease were identified; 148 patients were LTBI positive and 84 were LTBI negative. Patients not prescreened for LTBI made up 82.0% of observed TB disease cases (1057/1289). Adding the hypothetical maximum estimate for prevented cases decreased the percentage of patients who were not prescreened for LTBI to 61.7% [1057/(1289 + 424)]. Conclusions: One-fifth of patients were screened for LTBI prior to their active TB diagnosis. Assuming the upper bound of cases prevented through current screening, almost 62% of TB disease patients were never screened for LTBI. Future work to elucidate gaps in LTBI screening practices and to identify opportunities to improve screening guidelines is needed.

Multidrug Resistance of Escherichia coli From Outpatient Uncomplicated Urinary Tract Infections in a Large United States Integrated Healthcare Organization.

Background: Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multidrug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision making. Methods: We evaluated UPEC resistance over time by care setting (in-person vs virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021. Results: We included 174 185 individuals who had ≥1 UPEC uUTI (233 974 isolates) (92% female, 46% Hispanic, mean age 52 years [standard deviation 20]). Overall, prevalence of UPEC MDR decreased during the study period (13% to 12%) both in virtual and in-person settings (P for trend <.001). Resistance to penicillins overall (29%), coresistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving the 2 plus ≥1 antibiotic class were common (10%). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time and by care setting. Conclusions: We observed a slight decrease in both class-specific antimicrobial resistance and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX. Resistance patterns were consistent over time and similar in both in-person and virtual settings. Virtual healthcare may expand access to UTI care.

Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system.

BACKGROUND: In the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA. METHODS: In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2. FINDINGS: 7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6-77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9-93·8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89·6% (50·2-97·8). INTERPRETATION: In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test. FUNDING: US Centers for Disease Control and Prevention and US National Institutes of Health.

COVID-19 vaccine concerns of health care providers and ancillary staff.

A web-based survey was widely distributed between November 1st-December 27th, 2021, to health care providers and ancillary staff to assess reported COVID-19 vaccination of their children as well as their vaccine concerns. Fewer nurses and laboratory / radiology technicians reported COVID-19 vaccination of their adolescent children and intent to vaccinate their younger children compared to physicians and pharmacists, along with more frequently reported concern about anaphylaxis and infertility. Focused efforts to update ancillary staff as well as all health care providers on emerging COVID-19 vaccine safety information for children is crucial to promote strong COVID-19 vaccine recommendations. IMPACT: Nurses, laboratory technicians and radiology technicians frequently reported concern about anaphylaxis and infertility after COVID-19 vaccination despite reassuring safety data. Education of ancillary staff with emerging safety data is important to strengthen health care provider vaccine recommendations.

Influenza Vaccination Among Pregnant Women: Self-report Compared With Vaccination Data From Electronic Health Records, 2018-2020 Influenza Seasons.

OBJECTIVES: Having accurate influenza vaccination coverage estimates can guide public health activities. The objectives of this study were to (1) validate the accuracy of electronic health record (EHR)-based influenza vaccination data among pregnant women compared with survey self-report and (2) assess whether survey respondents differed from survey nonrespondents by demographic characteristics and EHR-based vaccination status. METHODS: This study was conducted in the Vaccine Safety Datalink, a network of 8 large medical care organizations in the United States. Using EHR data, we identified all women pregnant during the 2018-2019 or 2019-2020 influenza seasons. Surveys were conducted among samples of women who did and did not appear vaccinated for influenza according to EHR data. Separate surveys were conducted after each influenza season, and respondents reported their influenza vaccination status. Analyses accounted for the stratified design, sampling probability, and response probability. RESULTS: The survey response rate was 50.5% (630 of 1247) for 2018-2019 and 41.2% (721 of 1748) for 2019-2020. In multivariable analyses combining both survey years, non-Hispanic Black pregnant women had 3.80 (95% CI, 2.13-6.74) times the adjusted odds of survey nonresponse; odds of nonresponse were also higher for Hispanic pregnant women and women who had not received (per EHR data) influenza vaccine during current or prior influenza seasons. The sensitivity, specificity, and positive predictive value of EHR documentation of influenza vaccination compared with self-report were ≥92% for both survey years combined. The negative predictive value of EHR-based influenza vaccine status was 80.5% (95% CI, 76.7%-84.0%). CONCLUSIONS: EHR-based influenza vaccination data among pregnant women were generally concordant with self-report. New data sources and novel approaches to mitigating nonresponse bias may be needed to enhance influenza vaccination surveillance efforts.

Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system.

BACKGROUND: In the United States, oral nirmatrelvir-ritonavir (PaxlovidTM) is authorized for use among patients aged 12+ years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under current real-world prescribing practices in outpatient settings is unclear. METHODS: We undertook a matched observational cohort study of non-hospitalized cases with SARS-CoV-2 infection to compare outcomes among those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Cases were matched on testing date, age, sex, clinical status (including care received, presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination, Charlson comorbidity index, prior-year healthcare utilization, and body mass index. Primary analyses evaluated effectiveness of nirmatrelvir-ritonavir in preventing hospital admission or death within 30 days after a positive test. Secondary analyses evaluated effectiveness against intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test. We measured treatment effectiveness as (1-adjusted hazards ratio [aHR])*100%, estimating the aHR via Cox proportional hazards models. RESULTS: Analyses included 7,274 nirmatrelvir-ritonavir recipients and 126,152 non-recipients with positive results from SARS-CoV-2 tests undertaken in outpatient settings between 8 April and 7 October, 2022. Overall, 114,208 (85.6%) and 81,739 (61.3%) of 133,426 participants had received 2+ and 3+ COVID-19 vaccine doses, respectively. A total of 111,489 (83.6% of 133,426) cases were symptomatic at the point of testing, with 5,472 (75.2% of 7,274) treatment recipients and 84,657 (67.1% of 126,152) non-recipients testing within 0-5 days after symptom onset. Effectiveness in preventing hospital admission or death within 30 days after a positive test was 79.6% (95% confidence interval: 33.9% to 93.8%) for cases dispensed nirmatrelvir-ritonavir within 0-5 days after symptom onset; within the subgroup of cases tested 0-5 days after symptom onset and dispensed treatment on the day of their test, effectiveness was 89.6% (50.2% to 97.8%). Effectiveness declined to 43.8% (-33.3% to 81.7%) for treatment course dispensed 6+ days after symptom onset or to cases who were not experiencing acute clinical symptoms. Overall, for cases dispensed treatment at any time within their clinical course, effectiveness was 53.6% (6.6% to 77.0%). Effectiveness in preventing the secondary endpoint of intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test was 89.2% (-25.0% to 99.3%) for cases dispensed treatment 0-5 days after symptom onset and 84.1% (18.8% to 96.9%) for cases dispensed treatment at any time. Subgroup analyses identified similar effectiveness estimates among cases who had received 2+ or 3+ COVID-19 vaccine doses. IMPLICATIONS: In a setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvir-ritonavir 0-5 days after symptom onset was associated with substantial reductions in risk of hospital admission or death within 30 days after a positive outpatient SARS-CoV-2 test.

Reactions following Pfizer-BioNTech COVID-19 mRNA vaccination and related healthcare encounters among 7,077 children aged 5-11 years within an integrated healthcare system.

BACKGROUND: Studies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety. METHODS: We conducted an observational study using data from a digital survey and EHR of children aged 5-11 years vaccinated with Pfizer-BioNTech COVID-19 mRNA vaccine across Kaiser Permanente Southern California during November 4, 2021-February 28, 2022. Parents/guardians who enrolled their children were sent a 14-day survey on reactions. Survey results were combined with EHR, and medical encounters were described for children whose parents or guardians indicated seeking medical care for vaccine-related symptoms. This study describes self-reported reactions (local and systemic) and additional symptoms (chest pain, tachycardia, and pre-syncope). RESULTS: The study recruited 7,077 participants aged 5-11 years who received the Pfizer-BioNTech COVID-19 mRNA vaccine. Of 6,247 participants with survey responses after dose 1, 2,176 (35 %) reported at least one systemic reaction, and 1,076 (32 %) of 3,401 respondents following dose 2 reported at least one systemic reaction. Local reactions were reported less frequently following dose 2 (1,113, 33 %) than dose 1 (3,140, 50 %). The most frequently reported reactions after dose 1 were pain at the injection site (48 %), fatigue (20 %), headache (12 %), myalgia (9 %) and fever (5 %). The most frequently reported symptoms after dose 2 were also pain at the injection site (30 %), fatigue (19 %), headache (13 %), myalgia (10 %) and fever (9 %). Post-vaccination reactions occurred most frequently-one day following vaccination. Chest pain or tachycardia were reported infrequently (1 %). EHR demonstrated that parents rarely sought care for post-vaccination symptoms, and among those seeking care, the most common symptoms documented in EHR were fever and nausea, comprising <0.5 % of children. No encounters were related to myocarditis. CONCLUSION: While post-vaccination reactions to the Pfizer-BioNTech COVID-19 mRNA vaccine were common in children aged 5-11 years, our data showed that in most cases they were transient and did not require medical care.

Health Care Utilization in the 6 Months Following SARS-CoV-2 Infection.

Importance: 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. Objectives: 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. Design, Setting, and Participants: 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. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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.

Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment - California, December 2021-May 2022.

Nirmatrelvir/ritonavir (Paxlovid) is a combination protease inhibitor that blocks replication of SARS-CoV-2 (the virus that causes COVID-19) and has been shown to reduce the risk for hospitalization and death among patients with mild to moderate COVID-19 who are at risk for progression to severe disease* (1). In December 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for early treatment with Paxlovid among persons with mild to moderate cases of COVID-19 who are at high risk for progression to severe disease (2). FDA and a small number of published case reports have documented recurrence of COVID-19 symptoms or a positive viral test result (COVID-19 rebound) 2-8 days after recovery or a negative SARS-CoV-2 test result among patients treated with Paxlovid (3-7); however, large-scale studies investigating severe illness after Paxlovid treatment are limited. This study used electronic health record (EHR) data from a large integrated health care system in California (Kaiser Permanente Southern California [KPSC]) to describe hospital admissions and emergency department (ED) encounters related to SARS-CoV-2 infections during the 5-15 days after pharmacy dispensation of a 5-day treatment course of Paxlovid. Among 5,287 persons aged ≥12 years who received Paxlovid during December 31, 2021-May 26, 2022, 73% had received ≥3 doses of COVID-19 vaccine†, and 8% were unvaccinated. During the 5-15 days after Paxlovid treatment was dispensed, six hospitalizations and 39 ED encounters considered to be related to SARS-CoV-2 infection were identified, representing <1% of all patients to whom Paxlovid treatment was dispensed during the study period. Among these 45 persons, 21 (47%) were aged ≥65 years, and 35 (78%) had at least one underlying medical condition§ (8). This study found that hospitalization or ED encounters for COVID-19 during the 5-15 days after Paxlovid treatment was dispensed for mild to moderate COVID-19 illness were rarely identified. When administered as an early-stage treatment, Paxlovid might prevent COVID-19-related hospitalization among persons with mild to moderate cases of COVID-19 who are at risk for progression to severe disease.

The Childhood Vaccination Schedule and the Lack of Association With Type 1 Diabetes.

OBJECTIVES: Safety studies assessing the association between the entire recommended childhood immunization schedule and autoimmune diseases, such as type 1 diabetes mellitus (T1DM), are lacking. To examine the association between the recommended immunization schedule and T1DM, we conducted a retrospective cohort study of children born between 2004 and 2014 in 8 US health care organizations that participate in the Vaccine Safety Datalink. METHODS: Three measures of the immunization schedule were assessed: average days undervaccinated (ADU), cumulative antigen exposure, and cumulative aluminum exposure. T1DM incidence was identified by International Classification of Disease codes. Cox proportional hazards models were used to analyze associations between the 3 exposure measures and T1DM incidence. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated. Models were adjusted for sex, race and ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and study site. RESULTS: In a cohort of 584 171 children, the mean ADU was 38 days, the mean cumulative antigen exposure was 263 antigens (SD = 54), and the mean cumulative aluminum exposure was 4.11 mg (SD = 0.73). There were 1132 incident cases of T1DM. ADU (aHR = 1.01; 95% CI, 0.99-1.02) and cumulative antigen exposure (aHR = 0.98; 95% CI, 0.97-1.00) were not associated with T1DM. Cumulative aluminum exposure >3.00 mg was inversely associated with T1DM (aHR = 0.77; 95% CI, 0.60-0.99). CONCLUSIONS: The recommended schedule is not positively associated with the incidence of T1DM in children. These results support the safety of the recommended childhood immunization schedule.

Surveillance for Adverse Events After COVID-19 mRNA Vaccination.

Importance: Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy. Objectives: To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population. Design, Setting, and Participants: This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021. Exposures: Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2. Main Outcomes and Measures: Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted. Results: A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273. Conclusions and Relevance: In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.

Predictors of hepatitis A immunity in adults in California in order to better utilize hepatitis A vaccine.

BACKGROUND: Hepatitis A vaccine recommendations now include homelessness, illegal drug use, and HIV, as well as traditional risk factors and travel to areas endemic for hepatitis A. We examined a large diverse population for predictors of Hepatitis A immunity in order to better utilize Hepatitis A vaccine. METHODS: We performed a cross-sectional descriptive study of members of a large integrated health plan with a test for Hepatitis A Immunoglobulin G (IgG) between January 1st, 2007, and December 31st, 2017. Exclusion criteria included age <18 years, <6 months of continuous enrollment, and Hepatitis A vaccine prior to Hepatitis A test. Variables of interest were age, gender, primary language spoken, ethnicity/race, neighborhood household income, and history of travel or history of jaundice. Multivariable logistic regression was performed to evaluate the association of risk factors on Hepatitis A immunity. RESULTS: Of the 318,170 persons ≥ 18 years tested for Hepatitis A immunity, 155, 842 persons had a reactive Hepatitis A IgG test (49%). The lowest prevalence was for Whites at 28.1% followed by Blacks at 35.8%. Hispanics and Asian/Pacific Islanders had prevalence rates of 63% and 68.2% respectively. In adjusted analyses, Asian/Pacific Islanders, Hispanics and Blacks were 5.17, 3.44 and 1.42 times more likely to have Hepatitis A immunity than Whites. Those that spoke Spanish or language other than English or Spanish as their primary preferred language were 6.11 and 3.27 time more likely to have immunity than English speakers. Known travel history conferred a 2.16 likelihood of Hepatitis A immunity. CONCLUSIONS: Persons of Hispanic and Asian/Pacific Islander background as well as persons with a preferred spoken language other than English have a high prevalence of Hepatitis A immunity. Testing for Hepatitis A immunity prior to vaccination should be considered for these groups.

COVID-19 Vaccination Coverage Among Insured Persons Aged ≥16 Years, by Race/Ethnicity and Other Selected Characteristics - Eight Integrated Health Care Organizations, United States, December 14, 2020-May 15, 2021.

COVID-19 vaccination is critical to ending the COVID-19 pandemic. Members of minority racial and ethnic groups have experienced disproportionate COVID-19-associated morbidity and mortality (1); however, COVID-19 vaccination coverage is lower in these groups (2). CDC used data from CDC's Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020-May 15, 2021. Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson & Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine). Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020-May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated. As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%). Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%). Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%). Persons aged 18-24 years had the lowest ≥1-dose coverage (28.7%) among all age groups. Continued monitoring of vaccination coverage and efforts to improve equity in coverage are critical, especially among populations disproportionately affected by COVID-19.

Association Between Rotavirus Vaccination and Type 1 Diabetes in Children.

Importance: Because rotavirus infection is a hypothesized risk factor for type 1 diabetes, live attenuated rotavirus vaccination could increase or decrease the risk of type 1 diabetes in children. Objective: To examine whether there is an association between rotavirus vaccination and incidence of type 1 diabetes in children aged 8 months to 11 years. Design, Setting, and Participants: A retrospective cohort study of 386 937 children born between January 1, 2006, and December 31, 2014, was conducted in 7 US health care organizations of the Vaccine Safety Datalink. Eligible children were followed up until a diagnosis of type 1 diabetes, disenrollment, or December 31, 2017. Exposures: Rotavirus vaccination for children aged 2 to 8 months. Three exposure groups were created. The first group included children who received all recommended doses of rotavirus vaccine by 8 months of age (fully exposed to rotavirus vaccination). The second group had received some, but not all, recommended rotavirus vaccines (partially exposed to rotavirus vaccination). The third group did not receive any doses of rotavirus vaccines (unexposed to rotavirus vaccination). Main Outcomes and Measures: Incidence of type 1 diabetes among children aged 8 months to 11 years. Type 1 diabetes was identified by International Classification of Diseases codes: 250.x1, 250.x3, or E10.xx in the outpatient setting. Cox proportional hazards regression models were used to analyze time to type 1 diabetes incidence from 8 months to 11 years. Hazard ratios and 95% CIs were calculated. Models were adjusted for sex, race/ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and Vaccine Safety Datalink site. Results: In a cohort of 386 937 children (51.1% boys and 41.9% non-Hispanic white), 360 169 (93.1%) were fully exposed to rotavirus vaccination, 15 765 (4.1%) were partially exposed to rotavirus vaccination, and 11 003 (2.8%) were unexposed to rotavirus vaccination. Children were followed up a median of 5.4 years (interquartile range, 3.8-7.8 years). The total person-time follow-up in the cohort was 2 253 879 years. There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20.6 cases per 100 000 person-years. Compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio was 1.03 (95% CI, 0.62-1.72) for children fully exposed to rotavirus vaccination and 1.50 (95% CI, 0.81-2.77) for children partially exposed to rotavirus vaccination. Conclusions and Relevance: The findings of this study suggest that rotavirus vaccination does not appear to be associated with type 1 diabetes in children.

Order of Live and Inactivated Vaccines and Risk of Non-vaccine-targeted Infections in US Children 11-23 Months of Age.

BACKGROUND: Some findings from observational studies have suggested that recent receipt of live vaccines may be associated with decreased non-vaccine-targeted infection risk and mortality. Our objective was to estimate risk of non-vaccine-targeted infections based on most recent vaccine type (live vaccines only, inactivated vaccines only or both concurrently) received in US children 11-23 months of age. METHODS: We conducted a retrospective cohort study within the Vaccine Safety Datalink. We examined electronic health record and immunization data from children born in 2003-2013 who received 3 diphtheria-tetanus-acellular pertussis vaccines before their first birthday. We modeled vaccine type as a time-varying exposure and estimated risk of non-vaccine-targeted infections identified in emergency department and inpatient settings, adjusting for multiple confounders. RESULTS: Among 428,608 children, 48.9% were female, 4.9% had ≥1 immunization visit with live vaccines only and 10.3% had a non-vaccine-targeted infection. In males, lower risk of non-vaccine-targeted infections was observed following last receipt of live vaccines only or live and inactivated vaccines concurrently as compared with last receipt of inactivated vaccines only [live vaccines-only adjusted hazard ratio (aHR) = 0.83, 95% confidence interval (CI): 0.72-0.94; live and inactivated vaccines concurrently aHR: 0.91, 95% CI: 0.88-0.94]. Among females, last receipt of live and inactivated vaccines concurrently was significantly associated with non-vaccine-targeted infection risk (aHR = 0.94, 95% CI: 0.91-0.97 vs. last receipt of inactivated vaccines only). CONCLUSIONS: We observed modest associations between live vaccine receipt and non-vaccine-targeted infections. In this observational study, multiple factors, including healthcare-seeking behavior, may have influenced results.