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 SARSCoV-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.

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 There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (infection with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] or vaccination against coronavirus disease 2019 [COVID-19]). From a multi-site cohort of frontline workers, we examined the heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels.Methods Exposures included event count and event order, categorized into 7 permutations. Outcome was level of serum antibodies against receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding immunoglobulin). Means were examined up to 365 days after each of the first to seventh events.Results Analysis included 5793 participants measured from 7 August 2020 to 15 April 2023. Hybrid immunity from infection before 1 or 2 vaccine doses elicited modestly superior antibody responses after the second and third events (compared with infections or vaccine doses alone). This superiority was not repeated after additional events. Among adults infected before vaccination, adjusted geometric mean ratios (95% confidence interval [CI]) of anti-RBD early response (versus vaccinated only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (.81-.94), and 0.99 (.85-1.15) after the second to fifth 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 (.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the second to fifth events, respectively.Conclusions Evidence of heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy. In this adult cohort, hybrid immunity elicited superior SARS-CoV-2 serum antibody response compared with COVID-19 vaccination alone; however, this superiority was not repeated after >= 4 immunizing events. Associations differed by permutations of immunizing events. These findings could inform vaccination strategies.

Abstract Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018−19 (N = 723) and 2019−20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.

Background. Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance. Methods. This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged >= 18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was messenger RNA (mRNA) COVID-19 vaccination (2 or 3 monovalent doses). Odds of PCCs among vaccinated and unvaccinated persons were compared with logistic regression. Results. Of 936 participants, 23.6% reported PCCs and 83.2% were vaccinated. Participants who received 3 vaccine doses had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (adjusted odds ratio [95% confidence interval]: 0.37 [.16-.85], 0.56 [.32-.97], and 0.48 [.25-.91], respectively). Conclusions. COVID-19 vaccination protected against development of PCCs among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important PCCs prevention tool.

OBJECTIVES:Trivalent inactivated influenza vaccine effectiveness was low in a prospective cohort of healthcare personnel (HCP) in Israel from 2016 to 2019. We conducted a randomised immunogenicity trial of quadrivalent recombinant influenza vaccine (RIV4) and standard-dose inactivated influenza vaccine (IIV4) among frequently and infrequently vaccinated previous cohort participants. METHODS:From October 2019 to January 2020, we enrolled and randomly allocated HCP from two Israeli hospitals to receive IIV4 or RIV4. Hemagglutination inhibition (HAI) antibody titres against 2019-2020 vaccine reference influenza viruses were compared between vaccine groups using geometric mean titre (GMT) ratios from sera collected one-month post-vaccination and by frequency of vaccination in the past 5 years (>2 vs ≤2). RESULTS:Among 415 HCP, the GMT ratio comparing RIV4 to IIV4 was 2.0 (95% confidence interval [CI] 1.7-2.7) for A(H1N1)pdm09, 1.6 (95% CI: 1.3-1.9) for A(H3N2), 1.8 (95% CI: 1.4-2.2) for B(Yamagata), and 1.1 (95% CI: 0.9-1.4) for B(Victoria). Similarly, RIV4 elicited higher HAI titres than IIV4 against all 2019-2020 vaccine reference viruses except B(Victoria) among infrequently and frequently vaccinated HCP (lower bound of GMT ratio 95% CIs ≥1.0). CONCLUSION:RIV4 had improved immunogenicity for influenza vaccine strains among both infrequent and frequent vaccinees compared to standard-dose IIV4. CLINICAL TRIALS REGISTRATION:NCT04523324.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening testing is a recommended mitigation strategy for schools, although few descriptions of program implementation are available. Methods Kindergarten through 12th grade (K-12) students and staff practicing universal masking during the delta and omicron variant waves from five schools in Durham, North Carolina and eight schools in Kansas City, Missouri participated; Durham's program was structured as a public health initiative facilitated by school staff, and Kansas City's as a research study facilitated by a research team. Tests included school-based rapid antigen or polymerase chain reaction testing, at-home rapid antigen testing, and off-site nucleic acid amplification testing. Results We performed nearly 5700 screening tests on more than 1600 K-12 school students and staff members. The total cost for the Durham testing program in 5 public charter K-12 schools, each with 500-1000 students, was $246 587 and approximately 752 h per semester; cost per test was $70 and cost per positive result was $7076. The total cost for the Kansas City program in eight public K-12 schools was $292 591 and required approximately 537 h in personnel time for school-based testing; cost per test was $132 and cost per positive result was $4818. SARS-CoV-2 positivity rates were generally lower (0-16.16%) than rates in the community (2.7-36.47%) throughout all testing weeks. Conclusions and Relevance Voluntary screening testing programs in K-12 schools are costly and rarely detect asymptomatic positive persons, particularly in universally masked settings. We found that school-based SARS-CoV-2 screening testing in K-12 schools is costly and burdensome for personnel. Targeted testing such as diagnostic testing, test-to-stay, or test-to-play may provide better value, particularly when test supplies or personnel are limited.

Abstract 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.

SummaryVaccine-induced immunity may impact subsequentde novoresponses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants. Regardless of variant, we observed greater Spike-specific and neutralizing antibody responses in post-vaccination infections than in those who were infected without prior vaccination. Through analysis of variant-specific memory B cells as markers ofde novoresponses, we observed that Delta and Omicron BA.1 infections led to a marked shift in immunodominance in which some drifted epitopes elicited minimal responses, even in primary infections. Prior immunity through vaccination had a small negative impact on thesede novoresponses, but this did not correlate with cross-reactive memory B cells, arguing against competitive inhibition of naïve B cells. We conclude that dampenedde novoB cell responses against drifted epitopes are mostly a function of altered immunodominance hierarchies that are apparent even in primary infections, with a more modest contribution from pre-existing immunity, perhaps due to accelerated antigen clearance.

Abstract 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.

Abstract Background An estimated 1-3% of children with SARS-CoV-2 infection will develop Post-COVID Conditions (PCC). This study evaluates mRNA COVID-19 vaccine impact on likelihood of PCC in children. Methods A multi-site cohort of children enrolled 7/21/2021-9/1/2022 underwent weekly SARS-CoV-2 screening tests and were surveyed via self- or parental report 12/1/2022-5/31/2023 regarding PCC (defined as ≥1 new or on-going symptoms lasting ≥ 1 month after infection). Multivariable logistic regression was performed to estimate the occurrence of PCC by vaccination status among children aged 5–17 years whose first PCR-confirmed SARS-CoV-2 infection occurred in-study with Omicron variant, who completed the survey >60 days from infection, and who were vaccine age-eligible at time of infection per ACIP recommendations. Vaccination status was categorized as vaccinated (at least primary series completed >14 days before infection) and unvaccinated (no vaccine doses before infection). Vaccination status was verified through vaccine registry and/or medical records. Results Of 622 participants surveyed, 5% (n=28) had PCC (Table 1) and 67% (n=474) were vaccinated (Table 2). Surveys were completed a median (IQR) of 203.7 days (119.0–293.0) after infection. Children with non-Hispanic Black race/ethnicity and good/fair/poor self-rated baseline health were more likely to report PCC. Children aged 12-18 years, Non-Hispanic Asian and White children, those reporting symptomatic SARS-CoV-2 infection, and those with excellent/very good self-rated baseline health were more likely to report vaccination When comparing children with and without PCC symptoms, COVID-19 mRNA vaccination was associated with a decreased likelihood of >1 PCC symptom (aOR 0.66, 95% CI 0.43-0.99), >2 PCC symptoms (aOR 0.52, 95% 0.32-0.83), and respiratory PCC symptoms (aOR 0.53, 95% CI 0.33-0.87) (Table 3). Table 1.Characteristics of all study participants by report of Post-COVID Conditions (PCC) on survey, N=622. Table 2.Characteristics of all study participants by COVID-19 vaccination status, N=622. Table 3.Adjusted odds of Post-COVID conditions (PCC) by COVID-19 vaccination status. Conclusion In this study, mRNA COVID-19 vaccination appeared to be protective against PCC in children following Omicron SARS-CoV-2 infection. The adjusted ORs correspond to an estimated 34%, 48%, and 47% reduced likelihood of >1, >2, and respiratory PCC symptoms among vaccinated children, respectively. These findings support COVID-19 vaccination for children and may encourage increased pediatric vaccine uptake. Disclosures Lisa Gwynn, MBA, MSPH, Merck: Honoraria

The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine was recommended by CDC's Advisory Committee on Immunization Practices for persons aged 12-15 years (referred to as adolescents in this report) on May 12, 2021, and for children aged 5-11 years on November 2, 2021 (1-4). Real-world data on vaccine effectiveness (VE) in these age groups are needed, especially because when the B.1.1.529 (Omicron) variant became predominant in the United States in December 2021, early investigations of VE demonstrated a decline in protection against symptomatic infection for adolescents aged 12-15 years and adults* (5). The PROTECT† prospective cohort of 1,364 children and adolescents aged 5-15 years was tested weekly for SARS-CoV-2, irrespective of symptoms, and upon COVID-19-associated illness during July 25, 2021-February 12, 2022. Among unvaccinated participants (i.e., those who had received no COVID-19 vaccine doses) with any laboratory-confirmed SARS-CoV-2 infection, those with B.1.617.2 (Delta) variant infections were more likely to report COVID-19 symptoms (66%) than were those with Omicron infections (49%). Among fully vaccinated children aged 5-11 years, VE against any symptomatic and asymptomatic Omicron infection 14-82 days (the longest interval after dose 2 in this age group) after receipt of dose 2 of the Pfizer-BioNTech vaccine was 31% (95% CI = 9%-48%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. Among adolescents aged 12-15 years, adjusted VE 14-149 days after dose 2 was 87% (95% CI = 49%-97%) against symptomatic and asymptomatic Delta infection and 59% (95% CI = 22%-79%) against Omicron infection. Fully vaccinated participants with Omicron infection spent an average of one half day less sick in bed than did unvaccinated participants with Omicron infection. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

BACKGROUND Test-to-stay (TTS) is a strategy to limit school exclusion following an exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the use of TTS within universally masked kindergarten through 12th grade (K-12) school settings following household SARS-CoV-2 exposure. METHODS Three hundred twenty-two participants were enrolled. Serial rapid antigen testing was performed up to 15 days post-exposure. Analysis-eligible participants completed the 15-day testing protocol, tested positive any time during the testing window, or received a negative test on or after day 9. Primary outcomes included within-school tertiary attack rate (TAR) (test positivity among close contacts of positive TTS participants), and school days saved among TTS participants. RESULTS Seventy-three of 265 analysis-eligible participants tested positive for SARS-CoV-2 (secondary attack rate of 28% [95% CI: 16-63%]). Among 77 within-school close contacts, 2 were positive (TAR = 3% [95% CI: 1-5%]). Participant absences were limited to 338 days, resulting in 82% of 1849 school days saved. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY TTS facilitates continued in-person learning and can greatly reduce the number of missed school days. CONCLUSIONS Within universally masked K-12 schools, TTS is a safe alternative to school exclusion following household SARS-CoV-2 exposure.

OBJECTIVES: Masking is an essential coronavirus 2019 mitigation tool assisting in the safe return of kindergarten through 12th grade children and staff to in-person instruction; however, masking adherence, compliance evaluation methods, and potential consequences of surveillance are currently unknown. We describe 2 school districts' approaches to promote in-school masking and the consequent impact on severe acute respiratory syndrome coronavirus 2 secondary transmission. METHODS: Two North Carolina school districts developed surveillance programs with daily versus weekly interventions to monitor in-school masking adherence. Safety teams recorded the proportion of students and staff appropriately wearing masks and provided real-time education after observation of improper masking. Primary infections, within-school transmission, and county-level severe acute respiratory syndrome coronavirus 2 infection rates were assessed. RESULTS: Proper mask use was high in both intervention groups and districts. There were variations by grade level, with lower rates in elementary schools, and proper adherence being higher in the weekly surveillance group. Rates of secondary transmission were low in both districts with surveillance programs, regardless of intervention frequency. CONCLUSIONS: Masking surveillance interventions are effective at ensuring appropriate masking at all school levels. Creating a culture of safety within schools led by local leadership is important and a feasible opportunity for school districts with return to in-person school. In our study of schools with high masking adherence, secondary transmission was low.

OBJECTIVES We evaluated the safety and efficacy of a test-to-stay program for unvaccinated students and staff who experienced an unmasked, in-school exposure to someone with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serial testing instead of quarantine was offered to asymptomatic contacts. We measured secondary and tertiary transmission rates within participating schools and in-school days preserved for participants. METHODS Participating staff or students from universally masked districts in North Carolina underwent rapid antigen testing at set intervals up to 7 days after known exposure. Collected data included location or setting of exposure, participant symptoms, and school absences up to 14 days after enrollment. Outcomes included tertiary transmission, secondary transmission, and school days saved among test-to-stay participants. A prespecified interim safety analysis occurred after 1 month of enrollment. RESULTS We enrolled 367 participants and completed 14-day follow-up on all participants for this analysis. Nearly all (215 of 238, 90%) exposure encounters involved an unmasked index case and an unmasked close contact, with most (353 of 366, 96%) occurring indoors, during lunch (137 of 357, 39%) or athletics (45 of 357, 13%). Secondary attack rate was 1.7% (95% confidence interval: 0.6%-4.7%) based on 883 SARS-CoV-2 serial rapid antigen tests with results from 357 participants; no tertiary cases were identified, and 1628 (92%) school days were saved through test-to-stay program implementation out of 1764 days potentially missed. CONCLUSION After unmasked in-school exposure to SARS-CoV-2, even in a mostly unvaccinated population, a test-to-stay strategy is a safe alternative to quarantine.

OBJECTIVESThroughout the COVID-19 pandemic, masking has been a widely used mitigation practice in kindergarten through 12th grade (K–12) school districts to limit within-school transmission. Prior studies attempting to quantify the impact of masking have assessed total cases within schools; however, the metric that more optimally defines effectiveness of mitigation practices is within-school transmission, or secondary cases. We estimated the impact of various masking practices on secondary transmission in a cohort of K–12 schools.METHODSWe performed a multistate, prospective, observational, open cohort study from July 26, 2021 to December 13, 2021. Districts reported mitigation practices and weekly infection data. Districts that were able to perform contact tracing and adjudicate primary and secondary infections were eligible for inclusion. To estimate the impact of masking on secondary transmission, we used a quasi-Poisson regression model.RESULTSA total of 1 112 899 students and 157 069 staff attended 61 K–12 districts across 9 states that met inclusion criteria. The districts reported 40 601 primary and 3085 secondary infections. Six districts had optional masking policies, 9 had partial masking policies, and 46 had universal masking. In unadjusted analysis, districts that optionally masked throughout the study period had 3.6 times the rate of secondary transmission as universally masked districts; and for every 100 community-acquired cases, universally masked districts had 7.3 predicted secondary infections, whereas optionally masked districts had 26.4.CONCLUSIONSSecondary transmission across the cohort was modest (<10% of total infections) and universal masking was associated with reduced secondary transmission compared with optional masking.

Background. We sought to evaluate the impact of changes in estimates ofCOVID-19 vaccine effectiveness on the incidence of laboratory-confirmedinfection among frontline workers at high risk for SARS-CoV-2. Methods.We analyzed data from a prospective frontline worker cohort to estimatethe incidence of COVID-19 by month as well as the association ofCOVID-19 vaccination, occupation, demographics, physical distancing andmask use with infection risk. Participants completed baseline andquarterly surveys, and each week self-collected mid-turbinate nasalswabs and reported symptoms. Results. Among 1,018 unvaccinated and 3,531fully vaccinated workers, the monthly incidence of laboratory-confirmedSARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval[CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000person-weeks in June. By September 2021, when the Delta variantpredominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4)per 1000 person-weeks. In contrast, there was no reportable incidenceamong fully vaccinated participants at the end of January 2021, andincidence remained low until September 2021 when it rose modestly to 4.1(95% CI 1.9-3.8) per 1000. Below average facemask use was associatedwith a higher risk of infection for unvaccinated participants duringexposure to persons who may have COVID-19, and vaccinated participantsduring hours in the community. Conclusions. COVID-19 vaccination wassignificantly associated with a lower risk of SARS-CoV-2 infectiondespite Delta variant predominance. Our data demonstrate the addedprotective benefit of facemask use among both unvaccinated andvaccinated frontline workers.

Background Assessing the real-world effectiveness of COVID-19 vaccines and understanding the incidence and severity of SARS-CoV-2 illness in children are essential to inform policy and guide health care professionals in advising parents and caregivers of children who test positive for SARS-CoV-2. Objective This report describes the objectives and methods for conducting the Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT) study. PROTECT is a longitudinal prospective pediatric cohort study designed to estimate SARS-CoV-2 incidence and COVID-19 vaccine effectiveness (VE) against infection among children aged 6 months to 17 years, as well as differences in SARS-CoV-2 infection and vaccine response between children and adolescents. Methods The PROTECT multisite network was initiated in July 2021, which aims to enroll approximately 2305 children across four US locations and collect data over a 2-year surveillance period. The enrollment target was based on prospective power calculations and accounts for expected attrition and nonresponse. Study sites recruit parents and legal guardians of age-eligible children participating in the existing Arizona Healthcare, Emergency Response, and Other Essential Workers Surveillance (HEROES)-Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) network as well as from surrounding communities. Child demographics, medical history, COVID-19 exposure, vaccination history, and parents/legal guardians’ knowledge and attitudes about COVID-19 are collected at baseline and throughout the study. Mid-turbinate nasal specimens are self-collected or collected by parents/legal guardians weekly, regardless of symptoms, for SARS-CoV-2 and influenza testing via reverse transcription-polymerase chain reaction (RT-PCR) assay, and the presence of COVID-like illness (CLI) is reported. Children who test positive for SARS-CoV-2 or influenza, or report CLI are monitored weekly by online surveys to report exposure and medical utilization until no longer ill. Children, with permission of their parents/legal guardians, may elect to contribute blood at enrollment, following SARS-CoV-2 infection, following COVID-19 vaccination, and at the end of the study period. PROTECT uses electronic medical record (EMR) linkages where available, and verifies COVID-19 and influenza vaccinations through EMR or state vaccine registries. Results Data collection began in July 2021 and is expected to continue through the spring of 2023. As of April 13, 2022, 2371 children are enrolled in PROTECT. Enrollment is ongoing at all study sites. Conclusions As COVID-19 vaccine products are authorized for use in pediatric populations, PROTECT study data will provide real-world estimates of VE in preventing infection. In addition, this prospective cohort provides a unique opportunity to further understand SARS-CoV-2 incidence, clinical course, and key knowledge gaps that may inform public health. International Registered Report Identifier (IRRID) RR1-10.2196/37929

OBJECTIVES:We evaluated the impact of a test-to-stay (TTS) program on within-school transmission and missed school days in optionally masked kindergarten through 12th grade schools during a period of high community severe acute respiratory syndrome coronavirus 2 transmission. METHODS:Close contacts of those with confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for enrollment in the TTS program if exposure to a nonhousehold contact occurred between November 11, 2021 and January 28, 2022. Consented participants avoided school exclusion if they remained asymptomatic and rapid antigen testing at prespecified intervals remained negative. Primary outcomes included within-school tertiary attack rate (test positivity among close contacts of positive TTS participants) and school days saved among TTS participants. We estimated the number of additional school-acquired cases resulting from TTS and eliminating school exclusion. RESULTS:A total of 1675 participants tested positive or received at least 1 negative test between days 5 and 7 and completed follow-up; 92% were students and 91% were exposed to an unmasked primary case. We identified 201 positive cases. We observed a tertiary attack rate of 10% (95% confidence interval: 6%-19%), and 7272 (89%) of potentially missed days were saved through TTS implementation. We estimated 1 additional school-acquired case for every 21 TTS participants remaining in school buildings during the entire study period. CONCLUSIONS:Even in the setting of high community transmission, a TTS strategy resulted in substantial reduction in missed school days in optionally masked schools.

OBJECTIVES Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related quarantines, which are required after close contact with infected individuals, have substantially disrupted in-person education for kindergarten through 12th grade (K–12) students. In recent recommendations, shortened durations of quarantine are allowed if a negative SARS-CoV-2 test result is obtained at 5 to 7 days postexposure, but access to testing remains limited. We hypothesized that providing access to in-school SARS-CoV-2 testing postexposure would increase testing and reduce missed school days. METHODS This prospective cohort study was conducted in one large public K–12 school district in North Carolina and included 2 periods: preimplementation (March 15, 2021, to April 21, 2021) and postimplementation (April 22, 2021, to June 4, 2021), defined around initiation of an in-school SARS-CoV-2 testing program in which on-site access to testing is provided. Number of quarantined students and staff, testing uptake, test results, and number of missed school days were analyzed and compared between the preimplementation and postimplementation periods. RESULTS Twenty-four schools, including 12 251 in-person learners, participated in the study. During preimplementation, 446 close contacts were quarantined for school-related exposures; 708 close contacts were quarantined postimplementation. Testing uptake after school-related exposures increased from 6% to 40% (95% confidence interval: 23% to 45%) after implementation, and 89% of tests were conducted in-school. After in-school testing implementation, close contacts missed ∼1.5 fewer days of school (95% confidence interval: −2 to −1). CONCLUSIONS Providing access to in-school testing may be a worthwhile mechanism to increase testing uptake after in-school exposures and minimize missed days of in-person learning, thereby mitigating the pandemic’s ongoing impact on children.