BACKGROUND: Post-COVID conditions (PCC) have proven difficult to diagnose. In this retrospective observational study, we aimed to characterize the level of variation in PCC diagnoses observed across clinicians from a number of methodological angles and to determine whether natural language classifiers trained on clinical notes can reconcile differences in diagnostic definitions. METHODS: We used data from 519 primary care clinics around the United States who were in the American Family Cohort registry between October 1, 2021 (when the ICD-10 code for PCC was activated) and November 1, 2023. There were 6,116 patients with a diagnostic code for PCC (U09.9), and 5,020 with diagnostic codes for both PCC and COVID-19. We explored these data using 4 different outcomes: 1) Time between COVID-19 and PCC diagnostic codes; 2) Count of patients with PCC diagnostic codes per clinician; 3) Patient-specific probability of PCC diagnostic code based on patient and clinician characteristics; and 4) Performance of a natural language classifier trained on notes from 5,000 patients annotated by two physicians to indicate probable PCC. RESULTS: Of patients with diagnostic codes for PCC and COVID-19, 61.3% were diagnosed with PCC less than 12 weeks after initial recorded COVID-19. Clinicians in the top 1% of diagnostic propensity accounted for more than a third of all PCC diagnoses (35.8%). Comparing LASSO logistic regressions predicting documentation of PCC diagnosis, a log-likelihood test showed significantly better fit when clinician and practice site indicators were included (p < 0.0001). Inter-rater agreement between physician annotators on PCC diagnosis was moderate (Cohen's kappa: 0.60), and performance of the natural language classifiers was marginal (best AUC: 0.724, 95% credible interval: 0.555-0.878). CONCLUSION: We found evidence of substantial disagreement between clinicians on diagnostic criteria for PCC. The variation in diagnostic rates across clinicians points to the possibilities of under- and over-diagnosis for patients.

IMPORTANCE: Less than half of the US population with any mental health condition receives services. Cost is the most commonly cited barrier to treatment. OBJECTIVE: To examine whether service use and out-of-pocket expenditures among Medicare beneficiaries with depression changed after Medicare implemented equal cost-sharing for outpatient mental health and medical services (Medicare parity). DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used a single-group, interrupted time series design and examined data from the Medical Expenditure Panel Survey Household Component from 2008 to 2019. The sample included Medicare beneficiaries aged 65 years or older with depression. Data were analyzed from June 2, 2023, to June 17, 2024. EXPOSURE: Under the Medicare Improvements for Patients and Providers Act of 2008, beneficiary cost-sharing for outpatient mental health services decreased from 50% prior to 2010 to 20% in 2014, creating parity with equivalent medical care. MAIN OUTCOMES AND MEASURES: The primary outcomes were outpatient mental health service use, as assessed by mean use, proportion of beneficiaries with any use, and intensity of use (ie, mean use among users), and out-of-pocket expenditures. RESULTS: The analysis included 5831 Medicare beneficiaries. Using the Medical Expenditure Panel Survey person-level survey weights, this number corresponded to a nationally representative sample of 72 436 656 beneficiaries (median [IQR] age, 72 [68-79] years; 64.2%-72.2% female per study year). After Medicare parity, mean use of outpatient mental health services among beneficiaries with depression increased by 0.54 visits per year (95% CI, 0.31-0.76 visits per year), and proportion of use increased by 6.61% per year (95% CI, 2.23%-10.99% per year). Intensity of use decreased at parity by a factor of 0.90 (95% CI, 0.82-1.00) and increased after parity by a multiple of 1.07 per year (95% CI, 1.04-1.10 per year). Mean out-of-pocket expenditures for these services increased after parity by $12.25 per year (95% CI, $2.42-$22.08 per year). Sensitivity analysis using the 2016 US Preventive Services Task Force recommendation for routine adult depression screening indicated that the proportion of use increased 28.26% (95% CI, 24.33%-32.19%) once the recommendation was issued. CONCLUSIONS AND RELEVANCE: In this economic evaluation of Medicare parity, implementation of Medicare parity coupled with routine adult depression screening was associated with significant increases in outpatient mental health service use among Medicare beneficiaries with depression. These findings suggest that parity policies alone may not be sufficient to effectively address multiple barriers to mental health care but in tandem with physician screening, diagnosis, and referral practices, may increase the accessibility of mental health services.

PURPOSE: Chlamydia and gonorrhea are the 2 most common bacterial sexually transmitted infections in the United States. Nonadherence to the Centers for Disease Control and Prevention treatment guidelines remains a concern. We examined how well chlamydia and gonorrhea treatment in primary care settings adhered to guidelines. METHODS: We used electronic health records from the PRIME registry to identify patients with diagnosis codes or positive test results for chlamydia and/or gonorrhea from 2018 to 2022. Outcomes were the first dates of antibiotic administered within 30 days after a positive test result for the infection. Descriptive statistics were calculated for patient sociodemographic characteristics. We used a multivariate parametric accelerated failure time analysis with shared frailty modeling to assess associations between these characteristics and time to treatment. RESULTS: We identified 6,678 cases of chlamydia confirmed by a positive test and 2,206 cases of gonorrhea confirmed by a positive test; 75.3% and 69.6% of these cases, respectively, were treated. Females, individuals aged 10-29 years, suburban dwellers, and patients with chlamydia-gonorrhea coinfection had higher treatment rates than comparator groups. Chlamydia was infrequently treated with the recommended antibiotic, doxycycline (14.0% of cases), and gonorrhea was infrequently treated with the recommended antibiotic, ceftriaxone (38.7% of cases). Time to treatment of chlamydia was longer for patients aged 50-59 years (time ratio relative to those aged 20-29 years = 1.61; 95% CI, 1.12-2.30) and for non-Hispanic Black patients (time ratio relative to White patients = 1.17; 95% CI, 1.04-1.33). CONCLUSIONS: Guideline adherence remains suboptimal for chlamydia and gonorrhea treatment across primary care practices. Efforts are needed to develop interventions to improve quality of care for these sexually transmitted infections.

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and rifapentine arms was 3.1% (95% CI -13.8% to 20.0%). Safety outcomes were similar in the rifapentine/moxifloxacin regimen and control arms. Among participants with TB and diabetes, the rifapentine/moxifloxacin arm had fewest unfavorable outcomes and was safe. Our findings indicate that the rifapentine/moxifloxacin regimen can be used in persons with TB and diabetes.

BACKGROUND: Evaluation of optimal dosing has generally been inadequate during TB drug development. Fluoroquinolones are central to TB treatment. We aimed to determine the dose of levofloxacin needed to achieve maximal efficacy and acceptable safety and tolerability as part of a multidrug TB regimen. METHODS: Opti-Q was an international, multi-center, randomized, placebo-controlled, phase II trial. Eligible participants with TB resistant to isoniazid and rifampicin but susceptible to fluoroquinolones (MDR-TB) were randomized to receive one of four weight-adjusted once-daily doses of levofloxacin given for 24 weeks(168 doses): 11mg/kg(750mg), 14mg/kg(750mg/1000mg), 17 mg/kg(1000mg/1250mg) or 20mg/kg(1250mg/1500mg) alongside a multidrug regimen. The primary efficacy outcome was time to sputum culture conversion and the primary safety outcome was grade 3 or higher adverse events. FINDINGS: 111 participants were randomized from three sites in South Africa and Peru. 83(75%) had cavities on chest x-ray, 55(50%) had a smear grading of 3+, median BMI was 20.4 kg/m(2). Median levofloxacin AUC/MIC was 573, 633, 918 and 1343 across the four treatment arms. There was no difference in time to culture conversion on solid or liquid media by treatment arm (stratified log-rank p=0.282), by tertile of AUC/MIC (p=0.350), or by dose received (p=0.723); 69.3%, 74.8%, 70.6% and 78.3% achieved culture conversion after 8 weeks on solid media respectively across the treatment arms; 64.6%, 69.5%, 52.6% and 69.6% in liquid culture. More participants experienced a grade 3-5 adverse event by dose (37.0% and 16.0% in the highest and lowest dose groups respectively, p=0.042, Cochran-Armitage test for trend) and by tertile of AUC (p=0.011). INTERPRETATION: As part of a multidrug regimen, doses of levofloxacin above 1000mg resulted in greater exposures and increased frequency of adverse events but did not result in faster time to sputum culture conversion. A dose of 1000mg daily can achieve the target exposure in nearly all adults and was well tolerated. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT01918397.

IMPORTANCE: An estimated 1% to 3% of children with SARS-CoV-2 infection will develop post-COVID-19 condition (PCC). OBJECTIVE: To evaluate the odds of PCC among children with COVID-19 vaccination prior to SARS-CoV-2 infection compared with odds among unvaccinated children. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, children were enrolled in a multisite longitudinal pediatric cohort from July 27, 2021, to September 1, 2022, and followed up through May 2023. Analysis used a case (PCC reported)-control (no PCC reported) design and included children aged 5 to 17 years whose first real time-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection occurred during the study period, who were COVID-19 vaccine age-eligible at the time of infection, and who completed a PCC survey at least 60 days after infection. From December 1, 2022, to May 31, 2023, children had weekly SARS-CoV-2 testing and were surveyed regarding PCC (≥1 new or ongoing symptom lasting ≥1 month after infection). EXPOSURES: COVID-19 mRNA vaccination status at time of infection was the exposure of interest; participants were categorized as vaccinated (≥2-dose series completed ≥14 days before infection) or unvaccinated. Vaccination status was verified through vaccination cards or vaccine registry and/or medical records when available. MAIN OUTCOME AND MEASURES: Main outcomes were estimates of the odds of PCC symptoms. Multivariate logistic regression was performed to estimate the odds of PCC among vaccinated children compared with odds of PCC among unvaccinated children. RESULTS: A total of 622 participants were included, with 28 (5%) case participants and 594 (95%) control participants. Median (IQR) age was 10.0 (7.0-11.9) years for case participants and 10.3 (7.8-12.7) years for control participants (P = .37). Approximately half of both groups reported female sex (13 case participants [46%] and 287 control participants [48%]). Overall, 57% of case participants (16 children) and 77% of control participants (458 children) were vaccinated (P = .05). After adjusting for demographic characteristics, number of acute COVID-19 symptoms, and baseline health, COVID-19 vaccination was associated with decreased odds of 1 or more PCC symptom (adjusted odds ratio [aOR], 0.43; 95% CI, 0.19-0.98) and 2 or more PCC symptoms (aOR, 0.27; 95% CI, 0.10-0.69). CONCLUSIONS AND RELEVANCE: In this study, mRNA COVID-19 vaccination was associated with reduced odds of PCC in children. The aORs correspond to an estimated 57% and 73% reduced likelihood of 1 or more and 2 or more PCC symptoms, respectively, among vaccinated vs unvaccinated children. These findings suggest benefits of COVID-19 vaccination beyond those associated with protection against acute COVID-19 and may encourage increased pediatric uptake.

INTRODUCTION: Understanding sex and gender differences during outbreaks is critical to delivering an effective response. Although recommendations and minimum requirements exist, the incorporation of sex-disaggregated data and gender analysis into outbreak analytics and response for informed decision-making remains infrequent. A scoping review was conducted to provide an overview of the extent of sex-disaggregated data and gender analysis in outbreak response within low- and middle-income countries (LMICs). METHODS: Five databases were searched for peer-reviewed literature examining sex- and gender-specific outcomes for communicable disease outbreaks published in English between 1 January 2012 and 12 April 2022. An adapted version of the WHO's Gender Analysis Matrix was used to synthesise evidence, which was then mapped across four phases of the outbreak timeline: prevention, detection, treatment/management and recovery. RESULTS: 71 articles met inclusion criteria and were included in this review. Sex-, gender-, and pregnancy-related disparities were identified throughout all four phases of the outbreak timeline. These disparities encompassed a wide range of risk factors for disease, vulnerability, access to and use of services, health-seeking behaviour, healthcare options, as well as experiences in healthcare settings and health and social outcomes and consequences. CONCLUSION: Significant gender-evidence gaps remain in outbreak response. Evidence that is available illustrates that sex and gender disparities in outbreaks vary by disease, setting and population, and these differences play significant roles in shaping outbreak dynamics. As such, failing to collect, analyse or use sex-disaggregated data and gendered data during outbreaks results in less effective responses, differential adverse health outcomes, increased vulnerability among certain groups and insufficient evidence for effective prevention and response efforts. Systematic sex- and gender-based analyses to ensure gender-responsive outbreak prevention, detection, treatment/management and recovery are urgently needed.

BACKGROUND: The 2023-24 U.S. influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with co-circulation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-24 season. METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction (RT-PCR). Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus sub-type/lineage and A(H1N1)pdm09 genetic subclades. RESULTS: Among 6,589 enrolled patients, 1,770 (27%) tested positive for influenza including 796 A(H1N1)pdm09, 563 B/Victoria, and 323 A(H3N2). Vaccine effectiveness against any influenza illness was 41% (95% Confidence Interval [CI]: 32 to 49): 28% (95% CI: 13 to 40) against influenza A(H1N1)pdm09, 68% (95% CI: 59 to 76) against B/Victoria, and 30% (95% CI: 9 to 47) against A(H3N2). Statistically significant protection against any influenza was found for all age groups except adults aged 50-64 years. Lack of protection in this age group was specific to influenza A-associated illness. We observed differences in VE by birth cohort and A(H1N1)pdm09 virus genetic subclade. CONCLUSIONS: Vaccination reduced outpatient medically attended influenza overall by 41% and provided protection overall against circulating influenza A and B viruses. Serologic studies would help inform differences observed by age groups.

BACKGROUND: Infection by Cryptococcus gattii can lead to pulmonary or central nervous system (CNS) disease, or both. Whether site of infection and disease severity are associated with C. gattii species and lineages or with certain underlying medical conditions, or both is unclear. We conducted a retrospective cohort study to identify factors associated with site of infection and mortality among C. gattii cases. METHODS: We extracted data on 258 C. gattii cases from Australia, Canada and the United States reported from 1999 to 2011. We conducted unadjusted and multivariable logistic regression analyses to evaluate factors associated with site of infection and C. gattii mortality among hospitalized cases (N=218). RESULTS: Hospitalized C. gattii cases with CNS and other extrapulmonary disease were younger, more likely to reside in Australia and be infected with VGI lineage but less likely to have comorbidities and die as compared to pulmonary cases. The odds of having CNS and/or other extrapulmonary disease were 9 times higher in cases with VGI infection (aOR=9.21, 95%CI=3.28-25.89). Age >70 years (aOR=6.69, 95%CI=2.44-18.30), chronic lung disease (aOR=2.62, 95%CI=1.05-6.51) and an immunocompromised status (aOR=2.08, 95%CI=1.05-6.51) were associated with higher odds of C. gattii mortality. CONCLUSIONS: Among hospitalized cases, C. gattii species and lineage are associated with site of infection but not with the risk of death, whereas older age and comorbidities increase the risk of death.

To understand how COVID-19 vaccines impact infection risk in children <5 years, we assessed risk of SARS-CoV-2 infection from Sept 2022-April 2023 in three cohort studies. There was no difference in risk by vaccination status. While vaccines reduce severe disease, they may not reduce SARS-CoV-2 infections in young children.

BACKGROUND: Stigma and lack of social support are barriers to HIV prevention, especially among cisgender Black women in the United States. While HIV pre-exposure prophylaxis (PrEP) can decrease HIV transmission, PrEP initiation and adherence remains low among Black women, especially in the U.S. South. OBJECTIVES: The purpose of this study was to characterize experiences with stigma and social support among PrEP-naïve and PrEP-experienced Black cisgender women in Mississippi. DESIGN: Qualitative study in which semi-structured interviews and focus groups were conducted. METHODS: We purposively recruited PrEP-naïve cisgender Black women who met PrEP indications to participate in focus groups and all PrEP-experienced cisgender Black women at a sexual health clinic in Jackson, Mississippi to participate in one-on-one semi-structured interviews. Inductive thematic analysis was used to analyze focus group and interview transcripts. RESULTS: A total of 37 PrEP-naïve Black cisgender women participated across 6 focus groups and 8 PrEP-experienced cisgender Black women completed semi-structured interviews. Four themes were identified: (1) the intersection of gendered racism, discrimination, and HIV stigma, (2) enacted and anticipated PrEP stigma, (3) stigma mitigation strategies and PrEP adherence, and (4) social support's role in PrEP initiation and adherence. PrEP-naïve and -experienced Black women discussed the negative consequence that sexual stigmatization and gendered racism has on HIV testing. PrEP-naïve Black women discussed how HIV stigma decreases PrEP initiation. Conversely, PrEP-experienced Black women were able to identify strategies they utilized to mitigate stigma. PrEP-experienced Black women discussed how differing levels of social support impact their PrEP use. CONCLUSION: Improving social support and stigma mitigation strategies could help improve PrEP initiation and adherence among cisgender Black women at-risk of acquiring HIV in the U.S. South. Educating communities on PrEP, and training providers on stigma-mitigating strategies when serving Black women in the U.S. South who are seeking HIV prevention is paramount. | PrEP initiation and adherence among Black cisgender women in Mississippi: The role of HIV and PrEP stigma and social supportWhy was the study done?Stigma and lack of social support have been demonstrated as barriers to HIV prevention, especially among cisgender Black women in the United States (U.S.). While HIV pre-exposure prophylaxis (PrEP), a HIV prevention medication, has the ability to decrease HIV transmission, rates of starting PrEP remain low among Black women, especially in the U.S. South. Improving PrEP programs for US Black women calls for understanding how stigma and social support impact PrEP use among Black women.What did the researchers do?We recruited cisgender Black women who was eligible for PrEP but have never taken PrEP (PrEP-naïve) to participate in focus groups and cisgender Black women who have taken PrEP (PrEP-experienced) to participate in one-on-one in-depth interviews from healthcare clinics in Jackson, Mississippi. Inductive thematic analysis was used to analyze focus group and interview transcripts.What did the researchers find?A total of 37 Black cisgender women across six groups participated in focus groups and eight cisgender Black women were interviewed. PrEP-naïve women reported: · HIV stigma in the community, which can lead to anticipated PrEP stigma · Experiencing sex-based sexual stigmatization at provider’s offices when seeking HIV testing PrEP-experienced Black women reported: Experiencing stigma when disclosing their PrEP use, such as their family and friends thinking that the woman and/or her partner is living with HIV. PrEP-experienced Black women who were in serodifferent partnership and had others in their network who knew about PrEP received support to take PrEP.What do the findings mean?Improving social support and stigma mitigation strategies could help improve PrEP initiation and adherence among cisgender Black women at-risk of acquiring HIV in the U.S. South. This includes educating communities on HIV and PrEP, and training providers on stigma-mitigating strategies when serving Black women in the U.S. South. | eng

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

BACKGROUND: Previous estimates of vaccine effectiveness (VE) against asymptomatic influenza virus infection based on seroconversion have varied widely and may be biased. We estimated 2022-2023 influenza VE against illness and asymptomatic infection in a prospective cohort. METHODS: In the HEROES-RECOVER cohort, adults at increased occupational risk of influenza exposure across 7 US sites provided weekly symptom reports and nasal swabs for reverse transcription-polymerase chain reaction (RT-PCR) influenza testing. Laboratory-confirmed influenza virus infections were classified as symptomatic (≥1 symptom) or asymptomatic during the week of testing. Participants reported demographic information and vaccination through surveys; most sites verified vaccination through medical record and immunization registry review. Person-time was calculated as days from the site-specific influenza season start (September-October 2022) through date of infection, study withdrawal, or season end (May 2023). We compared influenza incidence among vaccinated versus unvaccinated participants overall, by symptom status, and by influenza A subtype, using Cox proportional hazards regression adjusted for site and occupation. We estimated VE as (1 - adjusted hazard ratio) × 100%. RESULTS: In total, 269 of 3785 (7.1%) participants had laboratory-confirmed influenza, including 263 (98%) influenza A virus infections and 201 (75%) symptomatic illnesses. Incidence of laboratory-confirmed influenza illness among vaccinated versus unvaccinated participants was 23.7 and 33.2 episodes per 100 000 person-days, respectively (VE: 38%; 95% CI: 15%-55%). Incidence of asymptomatic influenza virus infection was 8.0 versus 11.6 per 100 000 (VE: 13%; 95% CI: -47%, 49%). CONCLUSIONS: Vaccination reduced incidence of symptomatic but not asymptomatic influenza virus infection, suggesting that influenza vaccination attenuates progression from infection to illness.

BACKGROUND: Immunogenicity studies suggest that recombinant influenza vaccine (RIV) may provide better protection against influenza than standard-dose inactivated influenza vaccines (SD IIV). This randomized trial evaluated the relative vaccine effectiveness (VE) and immunogenicity of RIV versus SD IIV in frontline workers and students aged 18-64 years. METHODS: Participants were randomized to receive RIV or SD IIV and followed for reverse-transcription polymerase chain reaction (RT-PCR)-confirmed influenza during the 2022-2023 influenza season. Sera were collected from a subset of participants before and at 1 and 6 months postvaccination and tested by hemagglutination inhibition for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria and against cell-grown vaccine reference viruses for A/H1N1 and A/H3N2. RESULTS: Overall, 3988 participants were enrolled and vaccinated (25% of the trial sample size goal); RT-PCR-confirmed influenza occurred in 20 of 1963 RIV recipients and 28 of 1964 SD IIV recipients. Relative VE was 29% (95% confidence interval [CI], -26% to 60%). In the immunogenicity substudy (n = 118), the geometric mean titer ratio (GMTR) comparing RIV to SD IIV at 1 month was 2.3 (95% CI, 1.4-3.7) for cell-grown A/H1N1, 2.1 (95% CI, 1.3-3.4) for cell-grown A/H3N2, 1.1 (95% CI, .7-1.6) for B/Victoria, and 1.4 (95% CI, .9-2.0) for B/Yamagata. At 6 months, GMTRs were >1 against A/H1N1, A/H3N2, and B/Yamagata. CONCLUSIONS: Relative VE of RIV compared to SD IIV did not reach statistical significance, but RIV elicited more robust humoral immune responses to 2 of 4 vaccine viruses at 1 month and 3 of 4 viruses at 6 months after vaccination, suggesting possible improved and sustained immune protection from RIV. Clinical Trials Registration. NCT05514002.

Elevated body mass index (BMI) has been linked to severe influenza illness and impaired vaccine immunogenicity, but the relationship between BMI and clinical vaccine effectiveness (VE) is less well described. This secondary analysis of data from a test-negative study of outpatients with acute respiratory illness assessed BMI and VE against medically attended, PCR-confirmed influenza over seven seasons (2011-12 through 2017-18). Vaccination status was determined from electronic medical records (EMR) and self-report; BMI was estimated from EMR-documented height and weight categorized for adults as obesity (≥ 30 kg/m(2)), overweight (25-29 kg/m(2)), or normal and for children based on standardized z-scales. Current season VE by virus type/subtype was estimated separately for adults and children. Pooled VE for all seasons was calculated as 1-adjusted odds ratios from logistic regression with an interaction term for BMI and vaccination. Among 28,089 adults and 12,380 children, BMI category was not significantly associated with VE against outpatient influenza for any type/subtype. Adjusted VE against A/H3N2, A/H1N1pdm09, and B in adults ranged from 16-31, 46-54, and 44-57%, and in children from 29-34, 57-65, and 50-55%, respectively, across the BMI categories. Elevated BMI was not associated with reduced VE against laboratory confirmed, outpatient influenza illness.

Leptospirosis, an acute bacterial zoonotic disease, is endemic in Puerto Rico. Infection in approximately 10%-15% of patients with clinical disease progresses to severe, potentially fatal illness. Increased incidence has been associated with flooding in endemic areas around the world. In 2022, Hurricane Fiona, a Category 1 hurricane, made landfall and inundated Puerto Rico with heavy rainfall and severe flooding, increasing the risk for a leptospirosis outbreak. In response, the Puerto Rico Department of Health (PRDH) changed guidelines to make leptospirosis cases reportable within 24 hours, centralized the case investigation management system, and provided training and messaging to health care providers. To evaluate changes in risk for leptospirosis after Hurricane Fiona to that before the storm, the increase in cases was quantified, and patient characteristics and geographic distribution were compared. During the 15 weeks after Hurricane Fiona, 156 patients experienced signs and symptoms of leptospirosis and had a specimen with a positive laboratory result reported to PRDH. The mean weekly number of cases during this period was 10.4, which is 3.6 as high as the weekly number of cases during the previous 37 weeks (2.9). After Hurricane Fiona, the proportion of cases indicating exposure to potentially contaminated water increased from 11% to 35%, and the number of persons receiving testing increased; these factors likely led to the resulting overall surge in reported cases. Robust surveillance combined with outreach to health care providers after flooding events can improve leptospirosis case identification, inform clinicians considering early initiation of treatment, and guide public messaging to avoid wading, swimming, or any contact with potentially contaminated floodwaters.

Objectives. To compare the incidence, case-hospitalization rates, and vaccination rates of COVID-19 between people experiencing sheltered homelessness (PESH) and the broader community in Chicago, Illinois, and describe the impact of a whole community approach to disease mitigation during the public health emergency. Methods. Incidence of COVID-19 among PESH was compared with community-wide incidence using case-based surveillance data from March 1, 2020, to May 11, 2023. Seven-day rolling means of COVID-19 incidence were assessed for the overall study period and for each of 6 distinct waves of COVID-19 transmission. Results. A total of 774 009 cases of COVID-19 were detected: 2579 among PESH and 771 430 in the broader community. Incidence and hospitalization rates per 100 000 in PESH were more than 5 times higher (99.84 vs 13.94 and 16.88 vs 2.14) than the community at large in wave 1 (March 1, 2020-October 3, 2020). This difference decreased through wave 3 (March 7, 2021-June 26, 2021), with PESH having a lower incidence rate per 100 000 than the wider community (8.02 vs 13.03). Incidence and hospitalization of PESH rose again to rates higher than the broader community in waves 4 through 6 but never returned to wave 1 levels. Throughout the study period, COVID-19 incidence among PESH was 2.88 times higher than that of the community (70.90 vs 24.65), and hospitalization was 4.56 times higher among PESH (7.51 vs 1.65). Conclusions. Our findings suggest that whole-community approaches can minimize disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission between vulnerable populations and the broader community, and reinforce the benefits of a shared approach that include multiple partners when addressing public health emergencies in special populations. (Am J Public Health. Published online ahead of print August 28, 2024:e1-e9. https://doi.org/10.2105/AJPH.2024.307801).

Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. METHODS: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021-August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14-59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. RESULTS: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). CONCLUSIONS: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.

PURPOSE: COVID-19 is a condition that can lead to other chronic conditions. These conditions are frequently diagnosed in the primary care setting. We used a novel primary care registry to quantify the burden of post-COVID conditions among adult patients with a COVID-19 diagnosis across the United States. METHODS: We used the American Family Cohort, a national primary care registry, to identify study patients. After propensity score matching, we assessed the prevalence of 17 condition categories individually and cumulatively, comparing patients having COVID-19 in 2020-2021 with (1) historical control patients having influenza-like illness in 2018 and (2) contemporaneous control patients seen for wellness or preventive visits in 2020-2021. RESULTS: We identified 28,215 patients with a COVID-19 diagnosis and 235,953 historical control patients with influenza-like illness. The COVID-19 group had higher prevalences of breathing difficulties (4.2% vs 1.9%), type 2 diabetes (12.0% vs 10.2%), fatigue (3.9% vs 2.2%), and sleep disturbances (3.5% vs 2.4%). There were no differences, however, in the postdiagnosis monthly trend in cumulative morbidity between the COVID-19 patients (trend = 0.026; 95% CI, 0.025-0.027) and the patients with influenza-like illness (trend = 0.026; 95% CI, 0.023-0.027). Relative to contemporaneous wellness control patients, COVID-19 patients had higher prevalences of breathing difficulties and type 2 diabetes. CONCLUSIONS: Our findings show a moderate burden of post-COVID conditions in primary care, including breathing difficulties, fatigue, and sleep disturbances. Based on clinical registry data, the prevalence of post-COVID conditions in primary care practices is lower than that reported in subspecialty and hospital settings.

RATIONALE: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/ACTG A5349 represents the largest Phase 3 randomized controlled therapeutic trial to date for such investigation. OBJECTIVES: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure with efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. METHODS: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. MEASUREMENTS AND MAIN RESULTS: Among 2255 participants with 6978 plasma samples, pyrazinamide displayed 7-fold exposure variability (151-1053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in a therapeutic window of 231-355 mg·h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1000 mg would have permitted an additional 13.1% (n=96) participants allocated to the control and 9.2% (n=70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared to the current weight-banded dosing. CONCLUSIONS: Flat dosing of pyrazinamide at 1000 mg daily would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772.

BACKGROUND: In the United States, most chlamydia cases are reported from non-sexually transmitted disease clinics, and there is limited information focusing on the reasons for chlamydia testing in private settings. These analyses describe clinical visits to primary care providers where chlamydia testing was performed to help discern between screening and diagnostic testing for chlamydia. METHODS: Using the largest primary care clinical registry in the United States, the PRIME registry, chlamydia tests were identified using Current Procedural Terminology procedure codes and categorized as diagnostic testing for sexually transmitted infection (STI)-related symptoms, screening for chlamydia, or "other," based on Classification of Diseases, Tenth Revision Evaluation and Management codes selected for visits. RESULTS: Of 120,013 clinical visits with chlamydia testing between January 1, 2019, and December 31, 2022, 70.4% were women; 20.6% were with STI-related symptoms, 59.9% were for screening, and 19.5% for "other" reasons. Of those 120,013 clinical visits with chlamydia testing, the logit model showed that patients were significantly more likely to have STI-related symptoms if they were female than male, non-Hispanic Black than non-Hispanic White, aged 15 to 24 years than aged ≥45 years, and resided in the South than in the Northeast. CONCLUSION: It is important to know what proportion of chlamydial infections is identified through screening programs and to have this information stratified by demographics. The inclusion of laboratory results could further facilitate a better understanding of the impact of chlamydia screening programs on the identification and treatment of chlamydia in private office settings in the United States.

While the number of immunocompromised (IC) individuals continues to rise, the existing literature on influenza vaccine effectiveness (VE) in IC populations is limited. Understanding the vaccine effectiveness (VE) of the seasonal influenza vaccines in immunocompromised (IC) populations remains paramount. Using 2017–2018 US Flu VE Network data, we examined the VE of the 2017–2018 seasonal influenza vaccine against symptomatic influenza in outpatient settings among IC adults. We used logistic regression and adjusted for enrollment site, race, self-reported general health status, age, and onset date of symptoms. The VE among non-IC was 31% (95% CI: 22, 39) and among IC participants was −4% (95% CI: −66, 35), though the difference was not statistically significant. This study demonstrates the capacity to study a large IC population using an existing influenza VE network and contributes to the literature to support large, multicenter VE studies for IC populations. © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

Due to differences in chemical properties and half-lives, best practices for exposure assessment may differ for legacy versus novel brominated flame retardants (BFRs). Our objective was to identify the environment matrix that best predicted biomarkers of children's BFR exposures. Paired samples were collected from children, aged 3-6 years, and their homes including dust, a small piece of polyurethane foam from the furniture, and a handwipe and wristband from each child. Biological samples collected included serum, which was analyzed for 11 polybrominated diphenyl ethers (PBDEs), and urine, which was analyzed for tetrabromobenzoic acid (TBBA), a metabolite of 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB). Significant positive correlations were typically observed between BFRs measured in dust, handwipes and wristbands, though wristbands and handwipes tended to be more strongly correlated with one another than with dust. PBDEs, EH-TBB and BEH-TEBP were detected in 30% of the sofa foam samples, suggesting that the foam was treated with PentaBDE or Firemaster® 550/600 (FM 550/600). PBDEs were detected in all serum samples and TBBA was detected in 43% of urine samples. Statistically significant positive correlations were observed between the environmental samples and serum for PBDEs. Urinary TBBA was 6.86 and 6.58 times more likely to be detected among children in the highest tertile of EH-TBB exposure for handwipes and wristbands, respectively (95 % CI: 2.61, 18.06 and 1.43, 30.05 with p<0.001 and 0.02, respectively). The presence of either PentaBDE or FM 550/600 in furniture was also associated with significantly higher levels of these chemicals in dust, handwipes and serum (for PBDEs) and more frequent detection of TBBA in urine (p=0.13). Our results suggest children are exposed to a range of BFRs in the home, some of which likely originate from residential furniture, and that silicone wristbands are a practical tool for evaluating external exposure to both the legacy and novel BFRs.

BACKGROUND: Flu-like reactions can occur after exposure to rifampin, rifapentine, or isoniazid. Prior studies have reported the presence of antibodies to rifampin, but associations with underlying pathogenesis are unclear. METHODS: We evaluated PREVENT TB study participants who received weekly isoniazid + rifapentine for 3 months (3HP) or daily isoniazid for 9 months (9H) as treatment for M. tuberculosis infection. Flu-like reaction was defined as a grade ≥2 of any of flu-like symptoms. Controls (3HP or 9H) did not report flu-like reactions. We developed a competitive enzyme-linked immunosorbent assays (ELISA) to detect antibodies against rifapentine, isoniazid, rifampin, and rifapentine metabolite. RESULTS: Among 128 participants, 69 received 3HP (22 with flu-like reactions; 47 controls) and 59 received 9H (12 with flu-like reactions; 47 controls). In participants receiving 3HP, anti-rifapentine IgG was identified in 2/22 (9%) participants with flu-like reactions and 6/47 (13%) controls (P = 0.7), anti-isoniazid IgG in 2/22 (9%) participants with flu-like reactions and 4/47 (9%) controls (P = 0.9), and anti-rifapentine metabolite IgG in 2/47 (4%) controls (P = 0.9). Among participants receiving 9H, IgG and IgM anti-isoniazid antibodies were each present in 4/47 (9%) controls, respectively, but none among participants with flu-like reactions; anti-rifapentine IgG antibodies were not present in any participants with flu-like reactions or controls. CONCLUSIONS: We detected anti-rifapentine, anti-isoniazid, and anti-rifapentine metabolite antibodies, but the proportions of participants with antibodies were low, and did not differ between participants with flu-like reactions and those without such reactions. This suggests that flu-like reactions associated with 3HP and 9H were not antibody-mediated.

OBJECTIVE: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011-2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥ 90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and they resembled T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

BACKGROUND: There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (SARS-CoV-2 infection or COVID-19 vaccination). From a cohort of health care personnel, first responders, and other frontline workers in six US states, we examined heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. METHODS: Exposures included event-count (sum of infections and vaccine doses) and event-order, categorized into seven permutations of vaccination and/or infection. Outcome was level of serum binding antibodies against receptor binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding Ig), measured by enzyme-linked immunosorbent assay. Mean antibody levels were examined up to 365 days after each of the 1st-7th events. RESULTS: Analysis included 5,793 participants measured from August 7, 2020 to April 15, 2023. Hybrid immunity from infection before one or two vaccine doses elicited modestly superior antibody responses after the 2nd and 3rd events (compared to infections or vaccine-doses alone). This superiority was not evident after the 4th and 5th events (additional doses). Among adults infected before vaccination, adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (0.81-0.94), and 0.99 (0.85-1.15) after the 2nd-5th events, respectively. Post-vaccination infections elicited superior responses: adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were: 0.93 (0.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the 2nd-5th events, respectively. CONCLUSIONS AND RELEVANCE: Findings reflecting heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy.

IMPORTANCE: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. OBJECTIVE: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. EXPOSURE: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. MAIN OUTCOME AND MEASURES: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. RESULTS: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. CONCLUSION AND RELEVANCE: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

OBJECTIVES: Pediatric COVID-19 vaccine hesitancy and uptake is not well understood. Among parents of a prospective cohort of children aged 6 months-17 years, we assessed COVID-19 vaccine knowledge, attitudes, and practices (KAP), and uptake over 15 months. METHODS: The PROTECT study collected sociodemographic characteristics of children at enrollment and COVID-19 vaccination data and parental KAPs quarterly. Univariable and multivariable logistic regression models were used to test the effect of KAPs on vaccine uptake; McNemar's test for paired samples was used to evaluate KAP change over time. RESULTS: A total of 2,837 children were enrolled, with more than half (61 %) vaccinated by October 2022. Positive parental beliefs about vaccine safety and effectiveness strongly predicted vaccine uptake among children aged 5-11 years (aOR 13.1, 95 % CI 8.5-20.4 and aOR 6.4, 95 % CI 4.3-9.6, respectively) and children aged 12+ years (aOR 7.0, 95 % CI 3.8-13.0 and aOR 8.9, 95 % CI 4.4-18.0). Compared to enrollment, at follow-up parents (of vaccinated and unvaccinated children) reported higher self-assessed vaccine knowledge, but more negative beliefs towards vaccine safety, effectiveness, and trust in government. Parents unlikely to vaccinate their children at enrollment reported more positive beliefs on vaccine knowledge, safety, and effectiveness at follow-up. CONCLUSION: The PROTECT cohort allows for an examination of factors driving vaccine uptake and how beliefs about COVID-19 and the COVID-19 vaccines change over time. Findings of the current analysis suggest that these beliefs change over time and policies aiming to increase vaccine uptake should focus on vaccine safety and effectiveness.