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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.

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kurt T. Hegmann, MD serves as the editor-in-chief of the American College of Occupational and Environmental Medicine Guidelines; and Manjusha Gaglani, MD serves on the Texas Pediatric Society and Texas Chapter of the American Academy of Pediatrics. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Abt Global LLC. Published by Elsevier Ltd.. All rights reserved.)

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.

Background: The PROTECT study is a longitudinal cohort study initiated in July 2021 with weekly testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 4 states: Arizona, Florida, exas, and Utah. This study aims to examine vaccine-elicited antibody response against postvaccination SARS-CoV-2 infections., Methods: Children aged 5-11 years had serum collected 14-59 days after their second dose of monovalent Pfizer-BioNTech coronavirus disease 2019 messenger RNA vaccine. Vaccine-elicited antibodies were measured using the area under the curve (AUC) and end-point titer using enzyme-linked immunosorbent assay (receptor-binding domain [RBD] and S2) and surrogate neutralization assays against ancestral (WA1) and Omicron (BA.2)., Results: 79 vaccinated participants (33 [41.7%] female; median age, 8.8 years [standard deviation, 1.9 years]), 48 (60.8%) were from Tucson, Arizona; 64 (81.0%) were non-Hispanic white; 63 (80.8%) attended school in person; 68 (86.1%) did not have any chronic conditions; and 47 (59.5%) were infected after vaccination. Uninfected children had higher AUCs against WA1 ( P = .009) and Omicron ( P = .02). The geometric mean and surrogate neutralization titer above the limit of detection was 346.0 for WA1 and 39.7 for Omicron, an 8.7-fold decrease ( P < .001). After adjustment of covariates in the WA1-specific model, we observed a 47% reduction in the odds of postvaccination infection for every standard deviation increase in RBD AUC (aOR, 0.53 [95% confidence interval, .29-.97) and a 69% reduction in the odds of infection for every 3-fold increase in RBD end titer (0.31 [.06-1.57])., Conclusions: Children with higher antibody levels experienced a lower incidence of postvaccination SARS-CoV-2 infection., Competing Interests: Potential conflicts of interest. Z. J., L. L., S. F., G. N. A., L. O. are employees of Abt Associates who received funds for this work through a contract awarded by the CDC’s National Center for Immunization and Respiratory Diseases. L. Gwynn previously served as a consultant for Vaxelis Medical Advisory Group. M. G. reports receiving grants from the CDC, both directly and via subcontracts from Abt Associates and Vanderbilt University Medical Center to her institution, outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020)., Methods: In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4., Results: Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes., Conclusions: HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations., Competing Interests: Potential conflicts of interest. Dr. Naleway received funding from Pfizer and Vir Biotechnology for unrelated studies. The other authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We compared postinfection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (nAb) responses among children and adults while the D614G-like strain and Alpha, Iota, and Delta variants circulated., Methods: During August 2020-October 2021, households with adults and children were enrolled and followed in Utah, New York City, and Maryland. Participants collected weekly respiratory swabs that were tested for SARS-CoV-2 and had sera collected during enrollment and follow-up. Sera were tested for SARS-CoV-2 nAb by pseudovirus assay. Postinfection titers were characterized with biexponential decay models., Results: Eighty participants had SARS-CoV-2 infection during the study (47 with D614G-like virus, 17 with B.1.1.7, and 8 each with B.1.617.2 and B.1.526 virus). Homologous nAb geometric mean titers (GMTs) trended higher in adults (GMT = 2320) versus children 0-4 (GMT = 425, P = .33) and 5-17 years (GMT = 396, P = .31) at 1-5 weeks postinfection but were similar from 6 weeks. Timing of peak titers was similar by age. Results were consistent when participants with self-reported infection before enrollment were included (n = 178)., Conclusions: The SARS-CoV-2 nAb titers differed in children compared to adults early after infection but were similar by 6 weeks postinfection. If postvaccination nAb kinetics have similar trends, vaccine immunobridging studies may need to compare nAb responses in adults and children 6 weeks or more after vaccination., Competing Interests: Potential conflicts of interest. Unrelated to this work, MDK and MH received funding from Merck and Pfizer, and CAP has received personal compensation from McKesson Corporation within the past 3 years. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States., Methods: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers., Results: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09., Conclusions: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons., Clinical Trials Registration: NCT03722589., Competing Interests: Potential conflicts of interest. M. G. reports grants from the unrelated CDC (US Ambulatory Flu/COVID Vaccine Effectiveness Network, Hospitalized Adult Influenza Vaccine Effectiveness Network [HAIVEN], Refining Effectiveness Estimates of Influenza Vaccines Synergizing Epidemiolgy and Incidence Methods for Influenza and Other Acute Respiratory Viral Illness [SYNERGY] Studies), unrelated CDC-Abt Associates (Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel [RECOVER] and Pediatric Research Observing Trends and Exposures in COVID-19 Timelines [PROTECT] cohort studies), unrelated CDC–Vanderbilt University Medical Center (Influenza and Other Viruses in the Acutely Ill [IVY] Study), unrelated CDC-Westat (Virtual Network: Investigating the Risk of COVID-19-Associated Outcomes and COVID-19 Vaccine Effectiveness Using Integrated Medical and Public Health Records [VISION-COVID] Study), unrelated Janssen (RSV Severity Birth Cohort Study), and unrelated Pfizer (Education for Men B Vaccine in Adolescents); being the co-chair of the Texas Pediatric Society's (Texas Chapter of the American Academy of Pediatrics) Infectious Diseases and Immunization Committee (2016–2022). A. L. N. reports funding from Pfizer and Vir Biotechnology for unrelated studies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The reliability of sequence-based inference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with a reverse transcription-PCR cycle threshold of ≤30 underwent whole-genome sequencing. Intrahost single-nucleotide variants (iSNV) were identified at a ≥5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole-genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had ≥1 consensus sequence that differed by 1 to 2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and in 6 of 11 with distinct ones. In multiple-infection households, whole-genome consensus sequences differed by 0 to 1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. IMPORTANCE We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings.

Background: Healthcare personnel (HCP) are a priority group for annual influenza vaccination. Few studies have assessed the validity of recall of prior influenza vaccination status among HCP, especially for more than one preceding season., Methods: Using data from a randomized controlled trial of influenza vaccination among 947 HCP from two US healthcare systems, we assessed agreement between participant self-report and administrative record documentation of influenza vaccination status during the preceding five influenza seasons; kappa coefficients and sensitivity values were calculated. Administrative record documentation was considered the gold standard. Documented vaccination sources included electronic medical records, employee health records, outside immunization providers, and the state immunization information system., Results: Among 683 HCP with prior influenza immunization information, 89.7% (95% CI: 87.2%, 91.9%) of HCP were able to self-report their vaccination status for the season preceding the survey. By the fifth preceding season, 82.6% (95% CI: 79.5%, 85.3%) of HCP were able to self-report. Among HCP who self-reported their vaccination status, agreement between self-report and documented vaccination status ranged from 81.9% (95% CI: 77.2%, 86.7%) for the fifth season to 90.5% (95% CI: 87.2%, 93.9%) for the season preceding interview. HCP who received vaccine for only some of the preceding five seasons (18.3%) more commonly had ≥2 errors in their recall compared with those vaccinated all five preceding seasons (55.7% vs. 4.3%)., Conclusions: Self-reported vaccination status is a reliable source for historical influenza vaccination information among HCP who are consistently vaccinated but less reliable for those with a history of inconsistent vaccination., (© 2022 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2., Methods: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size., Results: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83)., Conclusions: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages., Competing Interests: Potential conflicts of interest. Unrelated to this work, Christina A. Porucznik discloses receipt of personal compensation from McKesson Corporation within the past 3 years. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Respiratory specimen collection materials shortages hampers severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We compared specimen alternatives and evaluated SARS-CoV-2 RNA stability under simulated shipping conditions. We compared concordance of RT-PCR detection of SARS-CoV-2 from flocked midturbinate swabs (MTS) in viral transport media (VTM), foam MTS without VTM, and saliva. Specimens were collected between August 2020 and April 2021 from three prospective cohorts. We compared RT-PCR cycle quantification ( C q ) for Spike (S), Nucleocapsid (N), and the Open Reading Frame 1ab (ORF) genes for flocked MTS and saliva specimens tested before and after exposure to a range of storage temperatures (4-30°C) and times (2, 3, and 7 days). Of 1,900 illnesses with ≥2 specimen types tested, 335 (18%) had SARS-CoV-2 detected in ≥1 specimen; 304 (91%) were concordant across specimen types. Among illnesses with SARS-CoV-2 detection, 97% (95% confidence interval [CI]: 94-98%) were positive on flocked MTS, 99% (95% CI: 97-100%) on saliva, and 89% (95% CI: 84-93%) on foam MTS. SARS-CoV-2 RNA was detected in flocked MTS and saliva stored up to 30°C for 7 days. All specimen types provided highly concordant SARS-CoV-2 results. These findings support a range of viable options for specimen types, collection, and transport methods that may facilitate SARS-CoV-2 testing during supply and personnel shortages. IMPORTANCE Findings from this analysis indicate that (1) self-collection of flocked and foam MTS and saliva samples is feasible in both adults and children, (2) foam MTS with VTM and saliva are both viable and reasonable alternatives to traditional flocked MTS in VTM for SARS-CoV-2 detection, and (3) these sample types may be stored and transported at ambient temperatures for up to 7 days without compromising sample quality. These findings support methods of sample collection for SARS-CoV-2 detection that may facilitate widespread community testing in the setting of supply and personnel shortages during the current pandemic.

Importance: Data about the risk of SARS-CoV-2 infection among children compared with adults are needed to inform COVID-19 risk communication and prevention strategies, including COVID-19 vaccination policies for children., Objective: To compare incidence rates and clinical characteristics of SARS-CoV-2 infection among adults and children and estimated household infection risks within a prospective household cohort., Design, Setting, and Participants: Households with at least 1 child aged 0 to 17 years in selected counties in Utah and New York City, New York, were eligible for enrollment. From September 2020 through April 2021, participants self-collected midturbinate nasal swabs for reverse transcription-polymerase chain reaction testing for SARS-CoV-2 and responded to symptom questionnaires each week. Participants also self-collected additional respiratory specimens with onset of COVID-19-like illness. For children unable to self-collect respiratory specimens, an adult caregiver collected the specimens., Main Outcomes and Measures: The primary outcome was incident cases of any SARS-CoV-2 infection, including asymptomatic and symptomatic infections. Additional measures were the asymptomatic fraction of infection calculated by dividing incidence rates of asymptomatic infection by rates of any infection, clinical characteristics of infection, and household infection risks. Primary outcomes were compared by participant age group., Results: A total of 1236 participants in 310 households participated in surveillance, including 176 participants (14%) who were aged 0 to 4 years, 313 (25%) aged 5 to 11 years, 163 (13%) aged 12 to 17 years, and 584 (47%) 18 years or older. Overall incidence rates of SARS-CoV-2 infection were 3.8 (95% CI, 2.4-5.9) and 7.7 (95% CI, 4.1-14.5) per 1000 person-weeks among the Utah and New York City cohorts, respectively. Site-adjusted incidence rates per 1000 person-weeks were similar by age group: 6.3 (95% CI, 3.6-11.0) for children 0 to 4 years, 4.4 (95% CI, 2.5-7.5) for children 5 to 11 years, 6.0 (95% CI, 3.0-11.7) for children 12 to 17 years, and 5.1 (95% CI, 3.3-7.8) for adults (≥18 years). The asymptomatic fractions of infection by age group were 52%, 50%, 45%, and 12% among individuals aged 0 to 4 years, 5 to 11 years, 12 to 17 years, and 18 years or older, respectively. Among 40 households with 1 or more SARS-CoV-2 infections, the mean risk of SARS-CoV-2 infection among all enrolled household members was 52% (range, 11%-100%), with higher risks in New York City compared with Utah (80% [95% CI, 64%-91%] vs 44% [95% CI, 36%-53%]; P < .001)., Conclusions and Relevance: In this study, children had similar incidence rates of SARS-CoV-2 infection compared with adults, but a larger proportion of infections among children were asymptomatic.

Background: RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4., Methods: During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population., Results: In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2-1.9) for A/H1N1, 3.0 (95% CI: 2.4-3.7) for A/H3N2, 1.1 (95% CI: .9-1.4) for B/Yamagata, and 1.1 (95% CI: .9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata., Conclusions: RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4., Clinical Trials Registration: NCT03722589., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

This study assesses the potential impact of drought on arsenic exposure from private domestic wells by using a previously developed statistical model that predicts the probability of elevated arsenic concentrations (>10 μg per liter) in water from domestic wells located in the conterminous United States (CONUS). The application of the model to simulate drought conditions used systematically reduced precipitation and recharge values. The drought conditions resulted in higher probabilities of elevated arsenic throughout most of the CONUS. While the increase in the probability of elevated arsenic was generally less than 10% at any one location, when considered over the entire CONUS, the increase has considerable public health implications. The population exposed to elevated arsenic from domestic wells was estimated to increase from approximately 2.7 million to 4.1 million people during drought. The model was also run using total annual precipitation and groundwater recharge values from the year 2012 when drought existed over a large extent of the CONUS. This simulation provided a method for comparing the duration of drought to changes in the predicted probability of high arsenic in domestic wells. These results suggest that the probability of exposure to arsenic concentrations greater than 10 μg per liter increases with increasing duration of drought. These findings indicate that drought has a potentially adverse impact on the arsenic hazard from domestic wells throughout the CONUS.

Objectives: Hurricane Harvey left a path of destruction in its wake, resulting in over 100 deaths and damaging critical infrastructure. During a disaster, public health surveillance is necessary to track emerging illnesses and injuries, identify at-risk populations, and assess the effectiveness of response efforts. The Centers for Disease Control and Prevention (CDC) and American Red Cross collaborate on shelter surveillance to monitor the health of the sheltered population and help guide response efforts., Methods: We analyzed data collected from 24 Red Cross shelters between August 25, 2017, and September 14, 2017. We described the aggregate morbidity data collected during Harvey compared with previous hurricanes (Gustav, Ike, and Sandy)., Results: Over one-third (38%) of reasons for visit were for health care maintenance; 33% for acute illnesses, which includes respiratory conditions, gastrointestinal symptoms, and pain; 19% for exacerbation of chronic disease; 7% for mental health; and 4% for injury. The Red Cross treated 41% of clients within the shelters; however, reporting of disposition was often missed. These results are comparable to previous hurricanes., Conclusion: The capacity of Red Cross shelter staff to address the acute health needs of shelter residents is a critical resource for local public health agencies overwhelmed by the disaster. However, there remains room for improvement because reporting remained inconsistent.

Perfluoroalkyl substances (PFAS) are chemicals used in the manufacture of consumer products. PFAS may act as endocrine disruptors, influencing metabolic pathways and weight-related outcomes. Previous studies observed an association between perfluorooctane sulfonic acid (PFOS) and higher gestational weight gain among under-/normal weight mothers. We analyzed associations of maternal serum pregnancy concentrations of PFAS with gestational weight gain (GWG) using data from 905 women in a subsample of the Avon Longitudinal Study of Parents and Children. Women were routinely weighed in antenatal check-ups; absolute GWG was determined by subtracting the first weight measurement from the last. Linear regression was used to explore associations of maternal PFAS concentrations with absolute GWG, stratified by prepregnancy body mass index. Associations of maternal PFOS, perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) concentrations with absolute GWG were null; 10% higher PFOS was associated with GWG of -0.03 kg (95% CI: -0.11, 0.06) among under-/normal weight mothers. Ten percent higher perfluorononanoic acid (PFNA) was associated with a higher GWG of 0.09 kg (95% CI: 0.02, 0.16) among under-/normal weight mothers. Overall, findings suggest no association between maternal PFOA, PFOS, and PFHxS concentrations and GWG, and a weak positive association between maternal PFNA and GWG., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Polychlorinated biphenyls (PCBs) are synthetic, organochlorine compounds previously used in industrial processes. Although banned in 1980's across Europe, these chemicals persist in the environment and are associated with adverse health outcomes in children. We investigated the association between in utero concentrations of PCBs and girls' body fatness. Concentrations of various PCB congeners (PCB 118, PCB 138, PCB 153, PCB 170, and PCB 180) were measured in maternal serum samples collected in the early 1990's. Body fatness was measured in the daughters at 9 y of age using body mass index (BMI) and dual-energy x-ray absorptiometry (DXA) for percent body fat. Using multivariable linear regression, we explored associations between prenatal PCB congener concentrations and body fatness outcomes. Among 339 mother-daughter dyads, the median and interquartile range (IQR) for PCB congeners ranged between 15.0 ng g -1 (11.0-20.8) for PCB 118 to 64.6 ng g -1 (48.6-86.3) for PCB 153. Among daughters, the median was 27.5% (21.7-34.6) for percent body fat, 39.6% (36.4-43.5) for percent trunk fat, 4.9 kg m -2 (3.5-7.0) for fat mass index and 18.1 kg m -2 (16.3-20.6) for body mass index. Multivariable-adjusted regression analyses showed little or no association between prenatal PCB concentrations with daughters' body fatness measures. Prenatal concentrations of PCB congeners were not strongly associated with measures of body fatness in girls., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Evidence indicates that in utero environmental exposures could influence reproduction in female offspring. Perfluoroalkyl substances (PFAS) are synthetic, ubiquitous endocrine disrupting chemicals that can cross the placental barrier. Lower levels of anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, are associated with reduced fertility. We investigated the association between in utero PFAS exposure and AMH levels in female adolescents using data from the Avon Longitudinal Study of Parents and Children, a British pregnancy cohort recruited between 1991 and 1992. Maternal serum samples were collected during pregnancy and analyzed for concentrations of commonly found PFAS-perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). AMH levels were measured in serum of female offspring (mean age, 15.4 years) and log-transformed for analyses. We used a sample of 446 mother-daughter dyads for multivariable linear regression analyses, controlling for maternal age at delivery, pre-pregnancy body-mass index, and maternal education. Multiple imputation was utilized to impute missing values of AMH (61.2%) and covariates. Median PFAS concentrations (ng/mL) were as follows: PFOS 19.8 (IQR:15.1, 24.9), PFOA 3.7 (IQR: 2.8, 4.8), PFHxS 1.6 (IQR: 1.2, 2.2), PFNA 0.5 (IQR: 0.4, 0.7). The geometric mean AMH concentration was 3.9 ng/mL (95% CI: 3.8, 4.0). After controlling for confounders, mean differences in AMH per one ng/mL higher PFOA, PFOS, PFHxS, and PFNA were 3.6% (95% CI: 1.4%, 8.6%), 0.7% (95% CI: 0.2%, 1.5%), 0.9% (95% CI: 0.4%, 2.2%), and 12.0% (95% CI: 42.8%, 66.8%) respectively. These findings suggest there is no association between in utero PFAS exposure and AMH levels in female adolescents., (Published by Elsevier Inc.)

Per- and polyfluoroalkyl substances (PFAS) have been widely used in commercial and industrial manufacturing processes since the 1950s. Inverse associations between prenatal exposure to PFAS and birth size have been found in populations around the globe. This study examined the association of prenatal maternal serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) and birth size in British boys. The study included 457 mother-son dyads participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Birth weight (g), crown to heel length (cm), and head circumference (cm) were collected at delivery. PFAS were detected in all maternal serum samples during pregnancy (median: 30 weeks gestation (interquartile range: 12-33)). Median concentrations (interquartile range) were 13.8 ng/mL (11.0, 17.7), 3.0 ng/mL (2.3, 3.8), 1.9 ng/mL (1.4, 2.5), and 0.4 ng/mL (0.3, 0.5) for PFOS, PFOA, PFHxS, and PFNA, respectively. In multivariable linear regression models, inverse associations were detected between PFOS (continuous) and birth weight (β = -8.50 g, 95% CI = -15.93, -1.07 g), crown to heel length (β = -0.04 cm, 95% CI = -0.08, -0.01 cm), and head circumference (β = -0.02 cm, 95% CI = -0.04, -0.002 cm). In conclusion, prenatal exposure to high levels of PFOS may be associated with reduced birth size in male infants., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: The developing brain is susceptible to exposure to neurodevelopmental toxicants such as pesticides., Aims: We explored associations of prenatal serum concentrations of hexachlorobenzene (HCB), beta-Hexachlorocyclohexane (β-HCH), 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) and 2,2-Bis(4-chlorophenyl-1,1,1-trichloroethane (p,p'-DDT) with maternal-reported measures of verbal and non-verbal communication in young girls., Study Design and Methods: We studied a sample of 400 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) using multivariable linear regression models adjusting for parity, Home Observation Measurement of the Environment (HOME) score, maternal age and education status, and maternal tobacco use during the first trimester of pregnancy., Exposure and Outcome Measures: Maternal serum samples (collected at median 15 wks. gestation [IQR 10, 28]) were assessed for selected organochlorine pesticide levels. Communication was assessed at 15 and 38 months, using adapted versions of the MacArthur Bates Communicative Development Inventories for Infants and Toddlers (MCDI)., Results: At 15 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had vocabulary comprehension and production scores approximately 16% (p = 0.007) lower than girls born to mothers with concentrations in the lowest tertile. This association varied by maternal parity in that the evidence was stronger for daughters of nulliparous mothers. At 38 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had mean adjusted intelligibility scores that were 3% (p = 0.03) lower than those born to mothers with concentrations in the lowest tertile; however, results did not vary significantly by parity. Maternal concentrations of β-HCH and p,p'-DDE were not significantly associated with MCDI scores at 15 or 36 months. p,p'-DDT had an inconsistent pattern of association; a significant positive association was observed between p,p'-DDT with verbal comprehension scores at 15 months; however, at 38 months a significant inverse association was observed for p,p'-DDT with communicative scores. This inverse association for p,p'-DDT among older girls tended to be stronger among daughters of mothers who had lower depression scores., Conclusions: Organochlorine pesticide exposure in utero may affect communication development., (Published by Elsevier B.V.)

Prenatal exposures to perfluoroalkyl substances (PFAS) have been associated with developmental outcomes in offspring. We found that prenatal concentrations of some PFAS may be associated with reduced bone mass and size in 17-year-old British girls, although it is not clear whether these associations are driven by body size., Purpose: PFAS are used to make protective coatings on common household products. Prenatal exposures have been associated with developmental outcomes in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between prenatal concentrations of PFAS and bone health in girls at 17 years of age and whether body composition can explain any associations., Methods: We measured concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) in maternal serum samples collected during pregnancy. We obtained bone health outcomes in the girls, such as bone mineral density, bone mineral content, bone area, and area-adjusted bone mineral content from whole-body dual-energy X-ray absorptiometry (DXA) scans. We used multivariable linear regression to explore associations between each PFAS and each bone health outcome with adjustment for important confounders such as girls' age at clinic visit, maternal education, and gestational age at sample collection. We also controlled for girls' height and lean mass to explore the role body composition had on observed associations., Results: Prenatal PFOS, PFOA, PFHxS, and PFNA concentrations were associated with inverse effects on bone size and mass after adjusting for important confounders. Conversely, PFNA was positively associated with area-adjusted bone mineral content. However, most significant associations attenuated after additional controlling for height and lean mass., Conclusions: Prenatal concentrations of some PFAS may be associated with reduced bone mass and size in adolescent girls, although it is not clear whether these associations are driven by body size.

Perfluoroalkyl substances (PFAS), found in many household products and classed as endocrine disrupting chemicals, can be transferred through the placenta and are associated with multiple developmental deficits in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between intrauterine exposure to PFAS and early communication development in 432 mother-daughter dyads at 15 and 38months of age. Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) were measured in maternal serum collected during pregnancy. Early communication development was measured with the ALSPAC-adapted MacArthur Communicative Development Inventories for Infants and Toddlers. The infant questionnaire measured verbal comprehension, vocabulary comprehension and production, nonverbal communication, and social development. The toddler questionnaire measured language, intelligibility, and communicative sub-scores. Multivariable linear regression was used to examine associations between each PFAS exposure and each communication sub-scale score. The association between maternal PFAS concentrations and early communication development at 15 and 38months of age varied by maternal age at delivery. In daughters of younger mothers (<25years of age), every 1ng/mL of PFOS was associated with a 3.82 point (95% confidence interval (CI): -6.18, -1.47) lower vocabulary score at 15months and a 0.80 point (95% CI: -1.74, 0.14) lower language score at 38months. Prenatal exposure to select PFAS was positively and negatively associated with communication development among girls, with inconsistent pattern of association across all measured PFAS and endpoints., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Growth hormone (GH) exerts diverse tissue-specific metabolic effects that are not revealed by global alteration of GH action. To study the direct metabolic effects of GH in the muscle, we specifically inactivated the growth hormone receptor (ghr) gene in postnatal mouse skeletal muscle using the Cre/loxP system (mGHRKO model). The metabolic state of the mGHRKO mice was characterized under lean and obese states. High-fat diet feeding in the mGHRKO mice was associated with reduced adiposity, improved insulin sensitivity, lower systemic inflammation, decreased muscle and hepatic triglyceride content, and greater energy expenditure compared with control mice. The obese mGHRKO mice also had an increased respiratory exchange ratio, suggesting increased carbohydrate utilization. GH-regulated suppressor of cytokine signaling-2 (socs2) expression was decreased in obese mGHRKO mice. Interestingly, muscles of both lean and obese mGHRKO mice demonstrated a higher interleukin-15 and lower myostatin expression relative to controls, indicating a possible mechanism whereby GHR signaling in muscle could affect liver and adipose tissue function. Thus, our study implicates skeletal muscle GHR signaling in mediating insulin resistance in obesity and, more importantly, reveals a novel role of muscle GHR signaling in facilitating cross-talk between muscle and other metabolic tissues.