During the COVID-19 pandemic, accurate measurement of vaccination status was important for guiding prevention efforts. We assessed the accuracy of electronic health record (EHR) COVID-19 vaccination compared with survey self-reported vaccination status using data from a cross-sectional study among pregnant women and non-pregnant adults in the Vaccine Safety Datalink between 2021 and 2022, where self-report was considered the reference standard. We measured the sensitivity and specificity of EHR vaccine data compared with the self-reported measure and estimated vaccination rates from EHR data. EHR data were obtained initially in November 2021, updated in April 2022, and record reviewed in July 2022. Vaccination coverage increased in pregnant/formerly pregnant women and non-pregnant adult respondents by 23.9% and 9.2%, respectively, over 9 months. Estimates of sensitivity based on initial EHR data were 66.0% and 77.3% for pregnant women and non-pregnant people overall and between 41% and 66% for pregnant, non-Hispanic Black, and Hispanic, Spanish-speaking respondents. With matured, chart reviewed EHR data from April 2022, the sensitivity and specificity of EHR vaccine status relative to self-report were > 93%. EHR data were a reasonable source of COVID-19 vaccination status during the pandemic and showed high accuracy with self-reported data after allowing EHR data to mature.

Vaccine-associated enhanced disease (VAED) was recognized as a theoretical risk when COVID-19 vaccines were authorized. Epidemiologic data can identify a signal for VAED if vaccine effectiveness (VE) is negative for preventing serious illness. In 2021, we initiated a cohort study to examine VAED indirectly by estimating VE against COVID-19 hospitalization and severe illness in the Vaccine Safety Datalink. The study cohort included VSD enrollees who were age-eligible to receive mRNA COVID-19 vaccine from February 2021-March 2023. Outcomes were initial COVID-19-associated hospital admission and severe in-hospital complications (acute respiratory distress or failure). VE was estimated by dose, variant period, and for early (14-119 d) and late (≥120 d) post-vaccination periods. VE was defined as 100*(1- adjusted hazard ratio). Relative VE (rVE) was estimated for bivalent vaccine versus ≥2 monovalent vaccine doses. The hospitalization analysis included all 16,027 enrollees with COVID-19 hospitalization and a 5% random sample of non-hospitalized enrollees who contributed person-time (n = 138,238). Two-dose original monovalent VE against hospitalization exceeded 90% in most age groups during the pre-Delta and Delta periods. VE was lower during the Omicron period. During the Omicron BA.2/BA.4/BA.5/XBB period, a fourth monovalent dose or bivalent dose generated VE of 59%-78% across age groups with modest waning. rVE was 48%-60% across age groups for bivalent vaccine vs. ≥2 original monovalent doses. Overall, the results were similar for VE against severe in-hospital complication. In conclusion, there was no signal for VAED during any variant period or for any specific dose of monovalent or bivalent vaccine.

OBJECTIVE:To assess any potential associations between epilepsy and up-to-date (UTD) vaccination status or cumulative aluminum exposures from vaccines among children aged less than 4 years. STUDY DESIGN:We conducted a case-control study in the Vaccine Safety Datalink cohort from 2008 through 2018. Epilepsy cases were identified up to 4 years of age by diagnosis codes with accompanying by antiseizure medication prescriptions. Controls had no diagnosis codes for epilepsy/seizures and no antiseizure medication before 4 years of age. Each case was matched to up to 10 controls. Cases and controls were matched on birthdate, sex, and Vaccine Safety Datalink site. Th exposures were age-specific UTD vaccination status categories and continuous, cumulative aluminum content per adjuvant formulation from vaccination. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals for the associated risk of epilepsy. Secondary analyses were performed by age subgroups and limited to children with epilepsy of unknown etiology.e RESULTS: The primary analysis included 2089 cases and 20 139 matched controls. No adjusted odds ratio for risk of epilepsy was greater than 1 either for UTD immunization status or for cumulative exposure to aluminum per mg increase per adjuvant formulation. In addition, there was no statistically significant relationship in analyses by age group or limitation to children with epilepsy of unknown etiology. CONCLUSIONS:Incident epilepsy was not associated with UTD vaccination status or cumulative vaccine aluminum exposure among children aged less than 4 years.

COVID-19 vaccination rates are decreasing despite vaccination being the most effective tool against severe disease from COVID-19. From October 1, 2022, to February 1, 2023, we conducted a cross-sectional study among adults in the Vaccine Safety Datalink about attitudes and beliefs regarding bivalent COVID-19 Omicron booster vaccine (hereafter referred to as COVID-19 bivalent vaccine) stratifying by vaccination status and race and ethnicity. Analysis was weighted for response and selection bias. The response rate was 27% (385/1430); 33% [95% CI: 21%-44%] of respondents were 'fully vaccinated' (had received COVID-19 bivalent vaccine), 54% [42%-67%] were partially vaccinated, and 13% [7%-19%] were unvaccinated. Fully vaccinated adults were more likely to consider COVID-19 bivalent vaccine 'very effective' (64%, [43%-86%]) at preventing hospitalization due to COVID-19 than partially (31%, [12%-50%]) or unvaccinated (2%, [0%-6%]) adults. Fully vaccinated adults were more likely to report COVID-19 bivalent vaccine was 'very safe' (83%, [69%-98%]) than partially (43%, [23%-63%]) or unvaccinated adults (2%, 0%-6%). Non-Hispanic White adults were more likely to report COVID-19 bivalent vaccine was 'very safe' (71%, [54%-87%]) than Non-Hispanic Black (36%, [21%-50%]) and Hispanic (26%, [7%-45%]) adults. A dose-response effect between vaccination status and perceptions of COVID-19 bivalent vaccine safety and effectiveness was observed, with fully vaccinated respondents having the most favorable attitudes. Racial and ethnic differences in perceived vaccine safety were also found. Improved communication about vaccine effectiveness and safety is key to improving low vaccination rates.

Introduction: The intersections of religion and vaccination became visible early in the COVID-19 pandemic. Yet, initial pandemic data reporting associations between religiosity and COVID-19 vaccine hesitancy is nearly 5 years old and has methodologic limitations. The aim of this study was to examine the associations between religious service attendance, COVID-19 attitudes, and COVID-19 vaccination at the midpoint of the COVID-19 public health emergency. Methods: A survey of Vaccine Safety Datalink members, purposefully sampled by race, ethnicity, language, and pregnancy status (N=2,856), was administered from November 2022 through February 2023. Data were analyzed through weighting and multivariable logistic regression. Results: Overall, 960 people (33%) responded; 22.8% (95% CI=15.2%, 30.3%) identified as Catholic, and 21.7% (95% CI=14.6%, 28.9%) identified as just Christian. Overall, 28.1% (95% CI=19.4%, 36.8%) reported never attending services, whereas 19.0% (95% CI=12.3%, 25.7%) attended weekly or more often. Compared with never attending services, religious service attendance weekly or more often was associated with increasing bivalent COVID-19 Omicron booster vaccine hesitancy (p<0.01) and decreasing trust in the Centers for Disease Control and Prevention for COVID-19 or COVID-19 vaccine information (p=0.033). Self-reported COVID-19 vaccination ever (AOR=0.65; 95% CI=0.23, 1.84) or any bivalent COVID-19 Omicron booster vaccination (AOR=0.36; 95% CI=0.06, 2.20) were not associated with religious service attendance weekly or more often, compared with never attending services. Conclusions: Observed associations between religious service attendance, vaccine attitudes, and trust in the Centers for Disease Control and Prevention encourage meaningfully redefining public health and faith community partnerships oriented toward COVID-19–related education and disease prevention.

BACKGROUND:Two respiratory syncytial virus (RSV) vaccines, Pfizer's Abrysvo and GSK's Arexvy, were licensed in 2023 in the U.S. However, population-based assessments of their safety in adults ≥60 years have not been widely published. We provide results from two complementary investigations of vaccinated adults in the Vaccine Safety Datalink (VSD). METHODS:The rapid cycle analysis (RCA) used a sequential cohort design and biweekly analyses of near real-time data to compare the incidence of 12 pre-specified outcomes in two post-vaccination risk intervals (1-21, 1-42 days) with the incidence in comparison intervals. The surveillance period was August 1, 2023, through September 28, 2024; nine of 13 VSD sites participated. Statistically significant signals were investigated by medical record review with re-analysis of confirmed outcomes. The self-controlled tree-based data mining analysis was designed to identify temporal clustering of ICD-10 diagnosis codes in the inpatient or emergency department settings 1-56 days post-vaccination, without pre-specifying outcomes or risk intervals. The study period was July 1, 2023, through December 31, 2023; 10 sites participated. RESULTS:The RCA analysis included 436,823 persons who received an RSV vaccine. No statistical signal was identified for 11 of 12 adverse events. A signal was detected for immune thrombocytopenic purpura following Arexvy, but re-analysis following medical record review did not confirm an association. The tree-based data mining analysis included 248,056 vaccinees, identified 53,734 counts of 3429 diagnosis codes, and identified no statistically significant clusters for either vaccine. CONCLUSIONS:These post-licensure safety assessments provide evidence supporting the safety of RSV vaccines in older adults. As more data accrue, additional monitoring is warranted for rare adverse events.

BACKGROUND:The cell culture-based inactivated influenza vaccine (ccIIV) was first approved for use in children aged 4-17 years in 2016 in the United States. The approved age indication for ccIIV was expanded to include children 6 months and older beginning the 2022-2023 season. There is limited real-world data on ccIIV effectiveness in children. We assessed ccIIV effectiveness using the test-negative design during the 2023-2024 season. METHODS:Patients aged 6 months to 64 years who sought outpatient or telehealth care for acute respiratory illness were actively recruited between October 2023 and May 2024. Symptom eligibility criteria included cough, with an illness duration of ≤ 7 days. Respiratory samples were tested by reverse transcription polymerase chain reaction to identify influenza cases. Vaccination dates and products were determined by immunization records. Analyses were restricted to ccIIV recipients and unvaccinated participants. Cell culture-based inactivated influenza vaccine effectiveness was estimated as [100% × (1 - odds ratio)] for vaccination in cases versus test-negative controls, with adjustment for age and calendar time. RESULTS:Among 1850 participants, 12% were age 6 months to 3 years, 32% were age 4-17 years, and 56% were age 18-64 years. Influenza was detected in 505 (27%) participants; 267 had influenza A/H1N1pdm09; 149 had influenza B; 56 had influenza A/H3N2; and 33 had influenza A with unknown subtype. A total of 470 (25%) received ccIIV. Among children (age 6 months to 17 years), ccIIV effectiveness was 64% [95% confidence interval (CI), 37%-81%] against influenza A/H1N1pdm09, 75% (95% CI, 43%-91%) against influenza B, and 76% (95% CI, 4%-97%) against influenza A/H3N2. Among adults (age 18-64 years), ccIIV effectiveness was 56% (95% CI, 31%-73%) against influenza A/H1N1pdm09, 62% (95% CI, 13%-86%) against influenza B, and 33% (95% CI, -62% to 76%) against influenza A/H3N2. Young children aged 6 months to 3 years had the highest point estimates (88%-98%). CONCLUSION:Cell culture-based inactivated influenza vaccine generated substantial real-world effectiveness against medically attended, laboratory-confirmed influenza in children and adults during a season when influenza A/H1N1pdm09 viruses predominated and influenza B and influenza A/H3N2 co-circulated at lower levels.

Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (<= 14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with >= 2 positive tests for longitudinal analyses, 105 (91%) experienced >= 1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza.

ABSTRACTPurposeVaccine‐associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS‐CoV‐2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID‐19).MethodsIn this cross‐sectional study, we assessed COVID‐19 severity as a proxy for VAED among 400 adults hospitalized for COVID‐19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID‐19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect.ResultsThe causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15–0.94) for ICU admission and 0.46 (95% CI, 0.25–0.76) for severe illness.ConclusionAmong hospitalized patients, reduced disease severity in those vaccinated against COVID‐19 supports the absence of VAED.

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 non respondents 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%; chi 21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; chi 21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; chi 21 = 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.

Purpose: This study assessed efficacy of one-time COVID-19 booster reminder/recall for booster eligible adolescents in a health-care system in Wisconsin.Methods: COVID-19 booster eligible patients aged 12-17 years were randomized 1:1 to receive one reminder/recall message from the health-care system using the parent's preferred communication method (intervention) or no reminder/recall (usual care) in May 2022. Results: Reminder/recall was sent to 2,146/4,296 (50%) adolescent patients. During the 90-day evaluation period following randomization, booster dose receipt was 2.0 percentage points (CI: 0.3%-3.7%) higher in the intervention (10.0%) versus usual care groups (8.0%). Among patients with >= 1 preventive visit during the evaluation period, uptake was 7.5 percentage points higher in the intervention (16.4%) versus usual care groups (8.9%).Discussion: A single COVID-19 booster dose reminder/recall resulted in a small but statistically significant increase in booster dose receipt, though uptake overall was low. Additional strategies are needed to increase uptake.(c) 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

In the United States, 2022-23 influenza activity began earlier than usual, increasing in October 2022, and has been associated with high rates of hospitalizations among children* (1). Influenza A(H3N2) represented most influenza viruses detected and subtyped during this period, but A(H1N1)pdm09 viruses cocirculated as well. Most viruses characterized were in the same genetic subclade as and antigenically similar to the viruses included in the 2022-23 Northern Hemisphere influenza vaccine (1,2). Effectiveness of influenza vaccine varies by season, influenza virus subtype, and antigenic match with circulating viruses. This interim report used data from two concurrent studies conducted at Marshfield Clinic Health System (MCHS) in Wisconsin during October 23, 2022-February 10, 2023, to estimate influenza vaccine effectiveness (VE). Overall, VE was 54% against medically attended outpatient acute respiratory illness (ARI) associated with laboratory-confirmed influenza A among patients aged 6 months-64 years. In a community cohort of children and adolescents aged <18 years, VE was 71% against symptomatic laboratory-confirmed influenza A virus infection. These interim analyses indicate that influenza vaccination substantially reduced the risk for medically attended influenza among persons aged <65 years and for symptomatic influenza in children and adolescents. Annual influenza vaccination is the best strategy for preventing influenza and its complications. CDC recommends that health care providers continue to administer annual influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating (2).

Introduction:Safety data on simultaneous vaccination (SV) with primary series monovalent COVID-19 vaccines and other vaccines are limited. We describe SV with primary series COVID-19 vaccines and assess 23 pre-specified health outcomes following SV among persons aged >5 years in the Vaccine Safety Datalink (VSD). Methods:We utilized VSD's COVID-19 vaccine surveillance data from December 11, 2020-May 21, 2022. Analyses assessed frequency of SV. Rate ratios (RRs) were estimated by Poisson regression when the number of outcomes was >5 across both doses, comparing outcome rates between COVID-19 vaccinees receiving SV and COVID-19 vaccinees receiving no SV in the 1-21 days following COVID-19 vaccine dose 1 and 1-42 days following dose 2 by SV type received ("All SV", "Influenza SV", "Non-influenza SV"). Results:SV with COVID-19 vaccines was not common practice (dose 1: 0.7 % of 8,455,037 persons, dose 2: 0.3% of 7,787,013 persons). The most frequent simultaneous vaccines were influenza, HPV, Tdap, and meningococcal. Outcomes following SV with COVID-19 vaccines were rare (total of 56 outcomes observed after dose 1 and dose 2). Overall rate of outcomes among COVID-19 vaccinees who received SV was not statistically significantly different than the rate among those who did not receive SV (6.5 vs. 6.8 per 10,000 persons). Statistically significant elevated RRs were observed for appendicitis (2.09; 95 % CI, 1.06-4.13) and convulsions/seizures (2.78; 95 % CI, 1.10-7.06) in the "All SV" group following dose 1, and for Bell's palsy (2.82; 95 % CI, 1.14-6.97) in the "Influenza SV" group following dose 2. Conclusion:Combined pre-specified health outcomes observed among persons who received SV with COVID-19 vaccine were rare and not statistically significantly different compared to persons who did not receive SV with COVID-19 vaccine. Statistically significant adjusted rate ratios were observed for some individual outcomes, but the number of outcomes was small and there was no adjustment for multiple testing. Published by Elsevier Ltd.

Abstract Background Several vaccines, including human papillomavirus (HPV), tetanus-diphtheria-acellular pertussis vaccine (Tdap), and meningococcal serogroup ACWY vaccine (MenACWY), are recommended at age 11-12 years. In the United States, uptake of these vaccines, particularly HPV, is suboptimal. Systems to identify and notify patients who are coming due or overdue for vaccinations (reminder/recall) have been shown to be an effective strategy to increase vaccination. We assessed the impact of sending informational vaccine notices to parents of 10-year-old patients on receipt of adolescent vaccines in a predominantly rural, regional healthcare system in northcentral Wisconsin. Methods 10-year-old patients with an upcoming 11th birthday (i.e., aged 10 years, 10 months or 10 years, 11 months) were identified at Marshfield Clinic Health System on a monthly basis and were randomized 1:1 to intervention (informational vaccine notice sent to the patient’s parent) vs. usual care (no notice). Randomization was stratified by rurality (rural, nonrural; defined by Rural-Urban Commuting Area Codes) and the parent’s preferred communication method (letter, text message, email). Receipt of adolescent vaccines (HPV, Tdap, MenACWY), as well as receipt of seasonal influenza vaccine and COVID-19 vaccine primary series, was assessed during the 90 days after randomization. Results From August 2021 through May 2022, 2,266 10-year-old patients were randomized (1,122 to the intervention and 1,144 to usual care) and 1,122 notices were sent to parents (576 letters, 544 text messages, and 2 emails). The majority of patients were non-Hispanic white (82%), lived in a rural area (63%), and approximately half were female (51%). Demographics did not vary by study arm. Receipt of HPV, Tdap, and MenACWY was 3.7 to 4.4 percentage points higher among patients randomized to the intervention vs. usual care (Table 1). No difference in uptake was observed for COVID-19 or influenza vaccines. Conclusion Informational notices sent to parents prior to their child’s 11th birthday resulted in modestly higher uptake of adolescent vaccines. Healthcare systems should consider sending vaccination notices, mailed or electronic, to parents whose children are coming due for recommended vaccines. Disclosures Kayla E. Hanson, MPH, Seqirus: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support

Background: Measles, mumps, and rubella vaccine (MMR) is routinely administered to children; however, adolescents and adults may receive MMR for various reasons. Safety studies in adolescents and adults are limited. We report on safety of MMR in this age group in the Vaccine Safety Datalink.Methods: We included adolescents (aged 9-17 years) and adults (aged >= 18 years) who received >= 1 dose of MMR from January 1, 2010-December 31, 2018. Pre-specified outcomes were identified by diagnosis codes. Clinically serious outcomes included anaphylaxis, encephalitis/myelitis, Guillain-Barre syndrome, immune thrombocytopenia, meningitis, and seizure. Non-serious outcomes were allergic reaction, arthropathy, fever, injection site reaction, lymphadenopathy, non-specific reaction, parotitis, rash, and syncope. All serious outcomes underwent medical record review. Outcome-specific incidence was calcu-lated in pre-defined post-vaccination windows. A self-controlled risk interval design was used to deter-mine the relative risk of each outcome in a risk window after vaccination compared to a more distal control window.Results: During the study period, 276,327 MMR doses were administered to adolescents and adults. Mean age of vaccinees was 34.8 years; 65.8 % were female; 53.2 % of doses were administered simultaneously with >= 1 other vaccine. Serious outcomes were rare, with incidence <= 6 per 100,000 doses for each out-come assessed, and none had a significant elevation in incidence during the risk window compared to the control window. Incidence of non-serious outcomes per 100,000 doses ranged from 3.4 for parotitis to 263.0 for arthropathy. Other common outcomes included injection site reaction and rash (157.0 and 112.9 per 100,000 doses, respectively). Significantly more outcomes were observed during the risk win-dow compared to the control window for all non-serious outcomes except parotitis. Some variability was observed by sex and age group.Conclusion: Serious outcomes after MMR are rare in adolescents and adults, but vaccinees should be counseled regarding anticipated local and systemic non-serious adverse events.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted.Methods Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020–April 2021 and September 2021–September 2022), were followed for 10–14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression.Findings 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49–68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74–100%) among those exposed to Omicron BA.5 (detected May – September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81–91%) and Omicron lineages (77%, 70–85%). Among Omicron BA.5-infected contacts, 48% (41–56%) reported fever, 63% (56–71%) cough, 22% (17–28%) shortness of breath, and 20% (15–27%) loss of/change in taste/smell.Interpretation The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease.Funding Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration.Key points ### Competing Interest StatementASL discloses personal fees to Sanofi and Roche outside the submitted work. HQM discloses grants from Seqirus outside the submitted work. YM discloses grants from Pfizer outside the submitted work. SR discloses grants from Biofire and consulting fees from Seqirus outside the submitted work. EAB discloses grants from Seqirus outside the submitted work. LS discloses consulting fees from CF foundation outside the submitted work. EA discloses grants from Pfizer and fees from Hillevax and Moderna outside the submitted work. SD discloses grants from Pfizer and Biofizer, and fees from Biofire, Diasorin Molecular, and Karius outside the submitted work. DP discloses grants from Pfizer and Roche outside the submitted work. CL discloses grants from AbbVie, AstraZeneca, bioMeriuex, Endpoint Helath, and Entegrion Inc, and investments in Bioscape Digital outside the submitted work. NH discloses grants from Quidel and Sanofi, and honoraria from Genentech outside the submitted work. CG discloses grants from Campbell Alliance/Syneos Health, Merck, Pfizer, and Sanofi, and fees from Sanofi and Pfizer outside the submitted work. No other authors disclose potential competing interests.### Funding StatementFunded by the Centers for Disease Control and Prevention and the Food and Drug Administration.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Vanderbilt University Medical Center, Marshfield Clinic Research Institute, or Westat IRBs gave ethical approval for this work. CDC determined these activities were conducted consistent with applicable federal law and CDC policy (see 45 C.F.R. part 46; 21 C.F.R. part 56).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors

The U.S. Food and Drug Administration authorized use of mRNA COVID-19 bivalent booster vaccines on August 31, 2022. Currently, CDC's clinical guidance states that COVID-19 and other vaccines may be administered simultaneously. At time of authorization and recommendations, limited data existed describing simultaneous administration of COVID-19 bivalent booster and other vaccines. We describe simultaneous influenza and mRNA COVID-19 bivalent booster vaccine administration between August 31-December 31, 2022, among persons aged >= 6 months in the Vaccine Safety Datalink (VSD) by COVID-19 bivalent booster vaccine type, influenza vaccine type, age group, sex, and race and ethnicity. Of 2,301,876 persons who received a COVID-19 bivalent booster vaccine, 737,992 (32.1%) received simultaneous influenza vaccine, majority were female (53.1%), aged >= 18 years (91.4%), and non-Hispanic White (55.7%). These findings can inform future VSD studies on simultaneous influenza and COVID-19 bivalent booster vaccine safety and coverage, which may have implications for immunization service delivery.

We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged [≥]50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms.

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 ver-sus 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 con-current 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.(c) 2022 The Authors. Published by Elsevier Ltd.