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.

Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

A Qualitative Study of Pediatric Residents' Experiences at Morning Report.

Objectives: Morning Report is a prevalent classroom learning activity in residency programs. Yet, its contribution to resident education remains unclear. Our objective was to explore pediatric residents' perceptions of the purpose of Morning Report as well as their experiences at Morning Report both as learners and resident presenters. Methods: We performed a qualitative study with a grounded theory approach using semi-structured focus groups of pediatric residents (November 2016-July 2017) from a large academic health center. We analyzed data with the constant comparative method, generating codes using an iterative approach and collecting data until reaching saturation. We identified major themes and resolved disagreements by consensus. Results: Twenty-six residents participated in five focus groups. Data analysis yielded four themes: Morning Report is Multipurpose, Socialization and Engagement Influence the Learning Environment, Potential for Emotional Discomfort, and Barriers to Prioritizing Morning Report Attendance. Residents felt the primary purpose of Morning Report was acquiring medical knowledge, but also acknowledged Morning Report's added benefits of providing an opportunity for socialization and a mental reprieve before work rounds. Residents felt Morning Report was educational when engaged in interactive discussion; however, it was challenging to meet the differing needs in this mixed learner level format. Some resident learners were hesitant to participate due to fears of being judged, and some resident presenters perceived a need to be topic experts. Clinical responsibilities and exhaustion following busy service rotations often precluded Morning Report attendance. Conclusion: Pediatric residents described numerous purposes of Morning Report, including opportunities for valuable learning. Self-perceived learning was positively influenced by engagement and a sense of connection and challenged by emotional discomfort at times. Future work can explore how to best promote engagement and foster a safe learning environment.

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.

Safety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink.

BACKGROUND: Traditional active vaccine safety monitoring involves pre-specifying health outcomes and biologically plausible outcome-specific time windows of concern, limiting the adverse events that can be evaluated. In this study, we used tree-based scan statistics to look broadly for >60,000 possible adverse events after bivalent COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees aged ≥5 years receiving Moderna or Pfizer-BioNTech bivalent COVID-19 vaccine through November 2022 were followed for 56 days post-vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within the hierarchical ICD-10-CM diagnosis code "tree" and temporally within post-vaccination follow-up. The conditional self-controlled tree-temporal scan statistic was used, conditioning on total number of cases of each diagnosis and total number of cases of any diagnosis occurring during the scanning risk window across the entire tree. P = 0.01 was the pre-specified cut-off for statistical significance. RESULTS: Analysis included 352,509 doses of Moderna and 979,189 doses of Pfizer-BioNTech bivalent vaccines. After Moderna vaccination, no statistically significant clusters were found. After Pfizer-BioNTech, there were clusters of unspecified adverse events (Days 1-3, p = 0.0001-0.0007), influenza (Days 35-56, p = 0.0001), cough (Days 44-55, p = 0.0002), and COVID-19 (Days 52-56, p = 0.0004). CONCLUSIONS: For Pfizer-BioNTech only, we detected clusters of: (1) unspecified adverse effects, as have been observed in other vaccine studies using this method, and (2) respiratory disease toward the end of follow-up. The respiratory clusters were likely due to overlap of follow-up with the spread of respiratory syncytial virus, influenza, and COVID-19, i.e., confounding by seasonality. The untargeted nature of the method and its inherent adjustment for the many diagnoses and risk intervals evaluated are unique advantages. Limitations include susceptibility to time-varying confounding, lower statistical power for assessing risks of specific outcomes than in traditional studies targeting fewer outcomes, and the possibility of missing adverse events not strongly clustered in time or within the "tree."

Medically Attended Acute Adverse Events in Pregnant People After Coronavirus Disease 2019 (COVID-19) Booster Vaccination.

In this multisite, observational, matched cohort study of more than 80,000 pregnant people, receipt of an mRNA monovalent coronavirus disease 2019 (COVID-19) booster vaccination in pregnancy was not associated with increased risk for thrombocytopenia, myocarditis, venous thromboembolism, ischemic stroke, or other serious adverse events within 21 or 42 days after booster vaccination. The mRNA monovalent COVID-19 booster in pregnancy was associated with an increased risk for medically attended malaise or fatigue within 7 days of vaccination (adjusted rate ratio [aRR] 3.64, 95% CI 2.42-5.48) and lymphadenopathy or lymphadenitis within 21 days (aRR 3.25, 95% CI 1.67-6.30) or 42 days (aRR 2.18, 95% CI 1.33-3.58) of vaccination. Our findings are consistent with prior evaluations of the primary COVID-19 vaccine series and are reassuring with respect to COVID-19 booster vaccination in pregnancy.

COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion.

Importance: Adherence to COVID-19 booster vaccine recommendations has lagged in pregnant and nonpregnant adult populations. One barrier to booster vaccination is uncertainty regarding the safety of booster doses among pregnant people. Objective: To evaluate whether there is an association between COVID-19 booster vaccination during pregnancy and spontaneous abortion. Design, Setting, and Participants: This observational, case-control, surveillance study evaluated people aged 16 to 49 years with pregnancies at 6 to 19 weeks' gestation at 8 health systems in the Vaccine Safety Datalink from November 1, 2021, to June 12, 2022. Spontaneous abortion cases and ongoing pregnancy controls were evaluated during consecutive surveillance periods, defined by calendar time. Exposure: Primary exposure was receipt of a third messenger RNA (mRNA) COVID-19 vaccine dose within 28 days before spontaneous abortion or index date (midpoint of surveillance period in ongoing pregnancy controls). Secondary exposures were third mRNA vaccine doses in a 42-day window or any COVID-19 booster in 28- and 42-day windows. Main Outcomes and Measures: Spontaneous abortion cases and ongoing pregnancy controls were identified from electronic health data using a validated algorithm. Cases were assigned to a single surveillance period based on pregnancy outcome date. Eligible ongoing pregnancy time was assigned to 1 or more surveillance periods as an ongoing pregnancy-period control. Generalized estimating equations were used to estimate adjusted odds ratios (AOR) with gestational age, maternal age, antenatal visits, race and ethnicity, site, and surveillance period as covariates and robust variance estimates to account for inclusion of multiple pregnancy periods per unique pregnancy. Results: Among 112 718 unique pregnancies included in the study, the mean (SD) maternal age was 30.6 (5.5) years. Pregnant individuals were Asian, non-Hispanic (15.1%); Black, non-Hispanic (7.5%); Hispanic (35.6%); White, non-Hispanic (31.2%); and of other or unknown (10.6%); and 100% were female. Across eight 28-day surveillance periods, among 270 853 ongoing pregnancy-period controls, 11 095 (4.1%) had received a third mRNA COVID-19 vaccine in a 28-day window; among 14 226 cases, 553 (3.9%) had received a third mRNA COVID-19 vaccine within 28 days of the spontaneous abortion. Receipt of a third mRNA COVID-19 vaccine was not associated with spontaneous abortion in a 28-day window (AOR, 0.94; 95% CI, 0.86-1.03). Results were consistent when using a 42-day window (AOR, 0.97; 95% CI, 0.90-1.05) and for any COVID-19 booster in a 28-day (AOR, 0.94; 95% CI, 0.86-1.02) or 42-day (AOR, 0.96; 95% CI, 0.89-1.04) exposure window. Conclusions and Relevance: In this case-control surveillance study, COVID-19 booster vaccination in pregnancy was not associated with spontaneous abortion. These findings support the safety of recommendations for COVID-19 booster vaccination, including in pregnant populations.

Community perceptions of vaccine advocacy for children under five in rural Guatemala.

Historically, partnerships with community leaders (e.g., religious leaders, teachers) have been critical to building vaccination confidence, but leaders may be increasingly vaccine hesitant. In rural Guatemala, the extent of vaccine hesitancy among community leaders is unclear, as are their perceptions of advocacy for childhood vaccines. We sought to: (i) compare Guatemalan religious leaders' and community leaders' attitudes toward childhood vaccines, (ii) describe leaders' experiences and comfort with vaccination advocacy, and (iii) describe community members' trust in them as vaccination advocates. In 2019, we surveyed religious leaders, other community leaders, and parents of children under five in rural Guatemala. We recorded participant demographic information and assessed participant vaccine hesitancy regarding childhood vaccines. We analyzed data descriptively and via adjusted regression modeling. Our sample included 50 religious leaders, 50 community leaders, and 150 community members (response rate: 99%); 14% of religious leaders and community leaders were vaccine hesitant, similar to community members (P = 0.71). In the prior year, 47% of leaders had spoken about vaccines in their formal role; 85% felt responsible to do so. Only 28% of parents trusted politicians "a lot" for vaccine advice, versus doctors (72%; P < 0.01), nurses (62%; P < 0.01), religious leaders (49%; P < 0.01), and teachers (48%; P < 0.01). In this study, religious leaders and community leaders were willing but incompletely engaged vaccination advocates. Most community members trusted doctors and nurses a lot for vaccination advice; half trusted teachers and religious leaders similarly. Public health officials in rural Guatemala can complement efforts by doctors and nurses through partnerships with teachers and religious leaders to increase vaccination confidence and delivery.

Tdap vaccination during pregnancy and risk of chorioamnionitis and related infant outcomes.

INTRODUCTION: An increased risk of chorioamnionitis in people receiving tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy has been reported. The importance of this association is unclear as additional study has not demonstrated increased adverse infant outcomes associated with Tdap vaccination in pregnancy. METHODS: We conducted a retrospective observational cohort study of pregnant people ages 15-49 years with singleton pregnancies ending in live birth who were members of 8 Vaccine Safety Datalink (VSD) sites during October 2016-September 2018. We used a time-dependent covariate Cox model with stabilized inverse probability weights applied to evaluate associations between Tdap vaccination during pregnancy and chorioamnionitis and preterm birth outcomes. We used Poisson regression with robust variance with stabilized inverse probability weights applied to evaluate the association of Tdap vaccination with adverse infant outcomes. We performed medical record reviews on a random sample of patients with ICD-10-CM-diagnosed chorioamnionitis to determine positive predictive values (PPV) of coded chorioamnionitisfor "probable clinical chorioamnionitis," "possible clinical chorioamnionitis," or "histologic chorioamnionitis." RESULTS: We included 118,211 pregnant people; 103,258 (87%) received Tdap vaccine during pregnancy; 8098 (7%) were diagnosed with chorioamnionitis. The adjusted hazard ratio for chorioamnionitis in the Tdap vaccine-exposed group compared to unexposed was 0.96 (95% CI 0.90-1.03). There was no association between Tdap vaccine and preterm birth or adverse infant outcomes associated with chorioamnionitis. Chart reviews were performed for 528 pregnant people with chorioamnionitis. The PPV for clinical (probable or possible clinical chorioamnionitis) was 48% and 59% for histologic chorioamnionitis. The PPV for the combined outcome of clinical or histologic chorioamnionitis was 81%. CONCLUSIONS AND RELEVANCE: Tdap vaccine exposure during pregnancy was not associated with chorioamnionitis, preterm birth, or adverse infant outcomes. ICD-10 codes for chorioamnionitis lack specificity for clinical chorioamnionitis and should be a recognized limitation when interpreting results.

COVID-19 Vaccine Safety Surveillance in Early Pregnancy in the United States: Design Factors Affecting the Association Between Vaccine and Spontaneous Abortion.

In the Vaccine Safety Datalink (VSD), we previously reported no association between coronavirus disease 2019 (COVID-19) vaccination in early pregnancy and spontaneous abortion (SAB). The present study aims to understand how time since vaccine rollout or other methodological factors could affect results. Using a case-control design and generalized estimating equations, we estimated the odds ratios (ORs) of COVID-19 vaccination in the 28 days before a SAB or last date of the surveillance period (index date) in ongoing pregnancies and occurrence of SAB, across cumulative 4-week periods from December 2020 through June 2021. Using data from a single site, we evaluated alternative methodological approaches: increasing the exposure window to 42 days, modifying the index date from the last day to the midpoint of the surveillance period, and constructing a cohort design with a time-dependent exposure model. A protective effect (OR = 0.78, 95% confidence interval: 0.69, 0.89), observed with 3-cumulative periods ending March 8, 2021, was attenuated when surveillance extended to June 28, 2021 (OR = 1.02, 95% confidence interval: 0.96, 1.08). We observed a lower OR for a 42-day window compared with a 28-day window. The time-dependent model showed no association. Timing of the surveillance appears to be an important factor affecting the observed vaccine-SAB association.

Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink.

BACKGROUND: The Centers for Disease Control and Prevention's Vaccine Safety Datalink (VSD) has been performing safety surveillance for COVID-19 vaccines since their earliest authorization in the United States. Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. This study's objective was to use this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S) COVID-19 vaccines. METHODS: VSD enrollees receiving a first booster of COVID-19 vaccine through April 2, 2022 were followed for 56 days. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the follow-up period. The self-controlled tree-temporal scan statistic was used, conditioning on the total number of cases for each diagnosis. P-values were estimated by Monte Carlo simulation; p = 0.01 was pre-specified as the cut-off for statistical significance of clusters. RESULTS: More than 2.4 and 1.8 million subjects received Pfizer-BioNTech and Moderna boosters after an mRNA primary series, respectively. Clusters of urticaria/allergy/rash were found during Days 10-15 after the Moderna booster (p = 0.0001). Other outcomes that clustered after mRNA boosters, mostly with p = 0.0001, included unspecified adverse effects, common vaccine-associated reactions like fever and myalgia, and COVID-19. COVID-19 clusters were in Days 1-10 after booster receipt, before boosters would have become effective. There were no noteworthy clusters after boosters following primary Janssen vaccination. CONCLUSIONS: In this untargeted data-mining study of COVID-19 booster vaccination, a cluster of delayed-onset urticaria/allergy/rash was detected after the Moderna booster, as has been reported after Moderna vaccination previously. Other clusters after mRNA boosters were of unspecified or common adverse effects and COVID-19, the latter evidently reflecting immunity to COVID-19 after 10 days.

A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink.

BACKGROUND: Except for spontaneous reporting systems, vaccine safety monitoring generally involves pre-specifying health outcomes and post-vaccination risk windows of concern. Instead, we used tree-based data-mining to look more broadly for possible adverse events after Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees receiving ≥1 dose of COVID-19 vaccine in 2020-2021 were followed for 70 days after Pfizer-BioNTech or Moderna and 56 days after Janssen vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the post-vaccination follow-up period. We used the self-controlled tree-temporal scan statistic and TreeScan software. Monte Carlo simulation was used to estimate p-values; p = 0.01 was the pre-specified cut-off for statistical significance of a cluster. RESULTS: There were 4.1, 2.6, and 0.4 million Pfizer-BioNTech, Moderna, and Janssen vaccinees, respectively. Clusters after Pfizer-BioNTech vaccination included: (1) unspecified adverse effects, (2) common vaccine reactions, such as fever, myalgia, and headache, (3) myocarditis/pericarditis, and (4) less specific cardiac or respiratory symptoms, all with the strongest clusters generally after Dose 2; and (5) COVID-19/viral pneumonia/sepsis/respiratory failure in the first 3 weeks after Dose 1. Moderna results were similar but without a significant myocarditis/pericarditis cluster. Further investigation suggested the fifth signal group was a manifestation of mRNA vaccine effectiveness after the first 3 weeks. Janssen vaccinees had clusters of unspecified or common vaccine reactions, gait/mobility abnormalities, and muscle weakness. The latter two were deemed to have arisen from confounding related to practices at one site. CONCLUSIONS: We detected post-vaccination clusters of unspecified adverse effects, common vaccine reactions, and, for the mRNA vaccines, chest pain and palpitations, as well as myocarditis/pericarditis after Pfizer-BioNTech Dose 2. Unique advantages of this data mining are its untargeted nature and its inherent adjustment for the multiplicity of diagnoses and risk intervals scanned.

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

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

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.

Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination.

BACKGROUND: Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population. METHODS: Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 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 conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination. RESULTS: From December 14, 2020 - January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54). CONCLUSIONS: Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.

Safety of COVID-19 Vaccination in United States Children Ages 5 to 11 Years.

BACKGROUND AND OBJECTIVES: Limited postauthorization safety data for the Pfizer-BioNTech coronavirus disease 2019 vaccination among children ages 5 to 11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the United States coronavirus disease 2019 vaccination program in this age group. METHODS: We analyzed data from 3 United States safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the Centers for Disease Control and Prevention and Food and Drug Administration; and the Vaccine Safety Datalink, an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. RESULTS: Among 48 795 children ages 5 to 11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7578 adverse event reports; 97% were nonserious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in boys after dose 2 (reporting rate 2.2 per million doses). In the Vaccine Safety Datalink, no safety signals were detected in weekly sequential monitoring after administration of 726 820 doses. CONCLUSIONS: Safety findings for Pfizer-BioNTech vaccine from 3 United States monitoring systems in children ages 5 to 11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12 to 15 years.

Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink.

Importance: Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years. Objective: To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. Design, Setting, and Participants: This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022. Exposures: Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021. Main Outcomes and Measures: GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day. Results: From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66). Conclusions and Relevance: In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.