Coronavirus disease 2019 (COVID-19), school closures, and quarantines have had substantial impacts on students’ health and education.1–3 Clinical trials have shown severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines to be safe and efficacious for adults, adolescents, and young children.4 However, in some areas, vaccine uptake has been low among children and adolescents, especially compared with uptake in adults.1 Additionally, real-world vaccine effectiveness data among adolescents and implications for in-person education are lacking. We investigated the impact of COVID-19 vaccination on SARS-CoV-2 incidence and within-school transmission in a cohort of sixth through twelfth grade students.
Methods
We conducted a prospective cohort study of 1128 students (grades 6–12; ages 11–19) in a North Carolina private school from August 1, 2021 to November 12, 2021. During the 2020 to 2021 school year, the school employed a mask mandate and hybrid schedule, with only 2 documented occurrences of within-school transmission.
During the study period, the Centers for Disease Control and Prevention (CDC) classified SARS-CoV-2 county transmission as “high” and the delta variant comprised >99% of infections in the region.5 The study period began on August 1, 2021 (day 0), when athletic activities and mandatory reporting of infections began. Full-time in-person classes began on August 17, 2021. Cumulative incidence of infection was assessed on November 12, 2021 (day 103).
School nurses monitored reporting of SARS-CoV-2 infections, symptoms, and exposures. Symptomatic persons were required to undergo SARS- CoV-2 testing; postexposure testing was encouraged, but not required. For reported infections, a nurse conducted case interviews and contact tracing using current CDC guidance and classified each infection as primary (resulting from community exposure) or secondary (resulting from within-school transmission).6 Contacts who were vaccinated and/or had masked school exposure were not required to quarantine. School policy required universal masking indoors after August 9, 2021 and ventilation systems were upgraded with minimum efficiency reporting value 11 filters; high efficiency particulate air filters were not used. Physical distancing was minimal, and there was no routine surveillance testing for students or staff. At the time of data export, vaccination status had been confirmed with photo evidence of a completed series (2 doses) uploaded to an online portal.7
Deidentified data from case investigations and contact tracing were collected by school officials and provided to study investigators weekly. We computed descriptive statistics using R (version 4.1.0) and the survival package.8 Cumulative incidence and 95% confidence intervals (95% CIs) were calculated using a Kaplan-Meier estimator. One participant, who was no longer enrolled at the school, was censored on day 33. Unadjusted vaccine effectiveness (VE) against documented SARS-CoV-2 infection and symptomatic infection was calculated as In calculating VE against symptomatic infection, students with asymptomatic infection were right-censored at time of infection. The Duke University Institutional Review Board (Pro00108129) determined this study to be exempt.
Results
As of November 2021, 829 (73.5%) students were vaccinated and 299 (26.5%) were unvaccinated, with each group contributing 84 953 and 29 572 person-days to the study, respectively. Demographic characteristics of the students are shown in Supplemental Table 2. Twenty (6.7%) unvaccinated students reported an infection during the study period, of which 16 (80%) were symptomatic. Seven (0.8%) vaccinated students reported an infection, of which 5 (71%) were symptomatic. Of the 27 infections, only 2 were classified as within-school transmissions, both resulting from unmasked exposures to unvaccinated index cases (Supplemental Table 2). Unvaccinated students had 8.2 (95% CI, 3.5–19.4) times the incidence of documented infection and 9.2 (95% CI, 3.4–25.1) times the incidence of symptomatic infection compared with vaccinated students (Fig 1). Unadjusted VE was 87.8% (95% CI, 71.2%–94.8%) against documented infection and 89.1% (95% CI, 70.3%–96.0%) against symptomatic infection (Table 1). Due to varying vaccine eligibility in this group, a sensitivity analysis excluding sixth grade students indicated that there were no appreciable differences in the associations noted above (Supplemental Tables 3 and 4; Supplemental Fig 2).
SARS-CoV-2 infection among sixth to twelfth grade students by vaccination status. Cumulative incidence of documented SARS-CoV-2 infection among sixth to twelfth grade students, by vaccination status. Day 0 was August 1, 2021. Shaded areas indicate 95% confidence intervals. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
SARS-CoV-2 infection among sixth to twelfth grade students by vaccination status. Cumulative incidence of documented SARS-CoV-2 infection among sixth to twelfth grade students, by vaccination status. Day 0 was August 1, 2021. Shaded areas indicate 95% confidence intervals. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
SARS-CoV-2 Incidence and Vaccine Effectiveness Among Sixth to Twelfth Grade Students
| Number of Events | Total Person- Days at Risk | Incidence Rate per 1000 Person-Days | Incidence Rate Ratio (95% CI) | Vaccine Effectiveness,% (95% CI) | |
|---|---|---|---|---|---|
| Documented SARS-CoV-2 infectionsa | |||||
| Unvaccinated | 20 | 29 572 | 0.676 | 8.2 (3.5–19.4) | 87.8 (71.2–94.8) |
| Vaccinated | 7 | 84 953 | 0.082 | Reference | |
| Symptomatic SARS-CoV-2 infectionsb | |||||
| Unvaccinated | 16 | 29 572 | 0.541 | 9.2 (3.4–25.1) | 89.1 (70.3–96.0) |
| Vaccinated | 5 | 84 953 | 0.059 | Reference |
| Number of Events | Total Person- Days at Risk | Incidence Rate per 1000 Person-Days | Incidence Rate Ratio (95% CI) | Vaccine Effectiveness,% (95% CI) | |
|---|---|---|---|---|---|
| Documented SARS-CoV-2 infectionsa | |||||
| Unvaccinated | 20 | 29 572 | 0.676 | 8.2 (3.5–19.4) | 87.8 (71.2–94.8) |
| Vaccinated | 7 | 84 953 | 0.082 | Reference | |
| Symptomatic SARS-CoV-2 infectionsb | |||||
| Unvaccinated | 16 | 29 572 | 0.541 | 9.2 (3.4–25.1) | 89.1 (70.3–96.0) |
| Vaccinated | 5 | 84 953 | 0.059 | Reference |
CI, confidence interval; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Documented SARS-CoV-2 infection includes both symptomatic and asymptomatic infections.
Students with asymptomatic SARS-CoV-2 infection were censored at time of infection.
Discussion
Numerous studies have shown minimal secondary COVID-19 transmission in schools with mitigation measures.9,10 Nevertheless, the implications of student vaccination rates on COVID-19 incidence and transmission have been minimally described. In this cohort of more than 1000 sixth to twelfth grade students, vaccine effectiveness against documented SARS-CoV-2 infection was 88%, providing evidence that vaccination is a critical component of safely continuing in-person education. This finding is comparable to other studies conducted when the delta variant was widespread.1,3
In this cohort, unvaccinated students had 8 times higher incidence of documented infection and less than 1% of vaccinated students reported an infection. As 1 primary infection can trigger a substantial number of quarantines, these findings indicate that vaccination may play a critical role in minimizing disease and keeping students in school; however, this may not be generalizable to other schools with lower vaccination rates. Our study also suggests that vaccination in conjunction with school-based mitigation measures may reduce within-school transmission; both documented school-related infections were the result of unmasked exposures to unvaccinated index cases.
Our study has some limitations. First, we relied upon self-reported vaccination status, which may have resulted in misclassification bias. Second, due to the nature of the data provided, we were unable to adjust VE estimates for covariates and confounders. Third, students with prior SARS-CoV-2 infection were not excluded from the study; if seropositivity was disparate among vaccinated participants and unvaccinated participants, VE may be biased. Fourth, asymptomatic infections may have been missed, due to the lack of regular asymptomatic testing. Finally, this study was conducted before the first cases of the omicron variant in North Carolina and included students from 1 urban private school, so the generalizability of the results may be somewhat limited.
In conclusion, in this real-world prospective cohort study of 1128 students, vaccinations substantially reduced SARS-CoV-2 incidence among adolescents and, along with other mitigation measures, kept students safely in-school during a variant-driven community surge.
Acknowledgments
We thank Erin Campbell, MS, for providing editorial review and submission; and Eric Hedinger, MEd, Anne Worgan, RN, and Emily Rusniak, RN, for conducting contact tracing and collecting data.
Mr Thakkar conceptualized and designed the study, drafted the initial manuscript, reviewed and revised the manuscript, designed the data collection instruments, collected data, and conducted the initial analyses; Drs Benjamin and Brookhart, and Ms Erickson reviewed and revised the manuscript; Drs Zimmerman and Kalu conceptualized and designed the study, coordinated, and supervised data collection, and critically reviewed the manuscript for important intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
FUNDING: This work was funded by the Trial Innovation Network, which is an innovative collaboration addressing critical roadblocks in clinical research and accelerating the translation of novel interventions into life-saving therapies sponsored by NCATS 5U25TR001608-05. This work was also funded by the National Institute of Child Health and Human Development contract HHSN275201000003I for the Pediatric Trials Network (PI Danny Benjamin). This work was also funded by the Rapid Acceleration of Diagnostics Underserved Populations, RADx-UP project: SARS-CoV-2 Screening and Diagnostic Testing for Return to K-12 Schools, NIH award #: 1OT2HD107559-01 (PI Danny Benjamin). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funded by the National Institutes of Health (NIH).
CONFLICT OF INTEREST DISCLOSURES: Dr Kalu reports consultancy for IPEC Experts LLC. Dr Zimmerman reports funding from the National Institutes of Health (NIH) and US Food and Drug Administration (FDA). Dr Benjamin reports consultancy for Allergan, Melinta Therapeutics, Sun Pharma Advanced Research Co. Dr Brookhart serves on scientific advisory committees for American Academy of Allergy, Asthma & Immunology, AbbVie, Amgen, Atara Biotherapeutics, Brigham and Women’s Hospital, Gilead, US Renal Data System, and Vertex; he receives consulting fees and owns equity in NoviSci and Target RWE. The remaining authors have no conflicts of interest to disclose.
Comments
Authors’ Response
As testing was required for all symptomatic students, it is unlikely that vaccine effectiveness against symptomatic infection could be biased by asymmetric testing uptake. In our manuscript, we acknowledged the inability to adjust for covariates or confounders, as well as the lack of screening testing are limitations of our study. Nevertheless, our finding of 88% vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is similar to the 92% adjusted vaccine effectiveness found in a study of adolescents who were tested weekly during the Delta variant surge.1 Some asymptomatic cases may have been missed, due to a lack of school-based screening testing, yet it is unlikely that such cases were missed differentially among vaccinated and unvaccinated students. Notably, the school’s guidance for post-exposure testing did not differ for vaccinated and unvaccinated students.
We acknowledge the recent publications suggesting natural SARS-CoV-2 infection may provide superior protection to vaccination at minimal cost. Although our study took place prior to the first documented cases of the Omicron variant, a recent report found two-dose vaccine effectiveness to be 50–70% against Omicron variant infection among 12–15 year old adolescents,2 and studies in adults have found vaccination to provide protective levels of antibodies against Omicron variant infection.3 Furthermore, although many coronavirus 2019 (COVID-19) cases in children are mild, COVID-19 can lead to severe outcomes, including hospitalization, multisystem inflammatory syndrome (MIS-C), and death.4 Additionally, some studies have proposed a link between SARS-CoV-2 infection and the development of other conditions, such as diabetes, in children.5 Vaccination remains a safe and effective method of protecting children from COVID-19 infection and subsequent severe outcomes.
References
1. Lutrick K, Rivers P, Yoo YM, et al. Interim estimate of vaccine effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine in preventing SARS-CoV-2 infection among adolescents aged 12–17 years — Arizona, July–December 2021. MMWR Morb Mortal Wkly Rep. 2021;70(5152):1761–1765. doi: 10.15585/mmwr.mm705152a2
2. Fowlkes AL, Yoon SK, Lutrick K, et al. Effectiveness of 2-dose BNT162b2 (Pfizer BioNTech) mRNA vaccine in preventing SARS-CoV-2 infection among children aged 5–11 years and adolescents aged 12–15 years — PROTECT Cohort, July 2021–February 2022. MMWR Morb Mortal Wkly Rep 2022;71(11):422–428. doi: 10.15585/mmwr.mm7111e1
3. Chen LL, Chu AW, Zhang RR, et al. Serum neutralisation of the SARS-CoV-2 sublineage BA.2. Lancet Microbe. Online first, March 28, 2022. doi: 10.1016/S2666-5247(22)00060-X
4. Marks KJ, Whitaker M, Agathis NT, et al. Hospitalization of infants and children aged 0–4 years with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 2020–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(11):429–436. doi: 10.15585/mmwr.mm7111e2
5. Barrett CE, Koyama AK, Alvarez P, et al. Risk for newly diagnosed diabetes >30 days after SARS-CoV-2 infection among persons aged <18 years — United States, March 1, 2020–June 28, 2021. MMWR Morb Mortal Wkly Rep. 2022;71:59–65. doi: 10.15585/mmwr.mm7102e2
Other strategies may also be rational for students in the Omicron era
Foremost, the vaccine effectiveness (VE) in reducing the SARS-CoV-2 incidence among adolescents may be substantially overestimated for several reasons, admitted by the Authors as well.
First, they were unable to adjust VE estimates for covariates and confounders, and more factors may contribute to the result of fewer infections in the vaccinated adolescents, e.g. being more health oriented and more adherent also to nonpharmacological mitigation measures.
Second, several asymptomatic infections have probably been missed, because of no regular asymptomatic testing, and the VE against asymptomatic infections is typically lower, and declines quicker than the VE against symptomatic cases,2 although it is well known that also asymptomatic individuals can transmit the virus.
Third, the study was conducted prior to the first cases of the Omicron variant in North Carolina, and it is established that the VE against Omicron is lower than against the Delta variant, moreover showing a rapid decrease to less than 20% at 15-19 weeks and to 9% at ≥25 weeks after two vaccine doses.3
In addition, new large studies raise some doubts about the strategy to avoid natural infection with the Omicron variant in pediatric age. Indeed, the Omicron and Delta variant infections are usually mild, or even pauci-/asymptomatic in children and adolescents (also in this prospective cohort study all the symptomatic students recovered with no hospitalization). Therefore, unless they live with unvaccinated fragile subjects, these students would pay a minimal price to acquire a robust and up-to-date immunity. According to the state of knowledge, this natural immunity is more lasting than the vaccine immunity, which declines rapidly,4 although the decrease is not as fast as what shown by 5-11 year olds.4
Due to the rapid vanishing of the vaccine immunity, its manteinance would require repeated boosters, whose sustainability over time is questionable, both because of the unknown effects of excessive injecting antigenic stimuli on the immune system, and because of the sum of adverse reactions following every new dose, which may be nontrivial in adolescents.5
References
1. Thakkar PV, Zimmerman KO, Brookhart MA, et al. COVID-19 incidence among 6th-12th grade students by vaccination status. Pediatrics. 2022; doi: 10.1542/peds.2022-056230
2. Abu-Raddad LJ, Chemaitelly H, Bertollini R; National Study Group for COVID-19 Vaccination. Waning mRNA-1273 Vaccine Effectiveness against SARS-CoV-2 Infection in Qatar. New Engl J Med. 2022 Mar 17;386(11):1091-1093. doi: 10.1056/NEJMc2119432. Epub 2022 Jan 26. PMID: 35081294; PMCID: PMC8809505.
3. Andrews N, Stowe J, Kirsebom F, et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. New Engl J Med. 2022 Mar 2. doi: 10.1056/NEJMoa2119451. Epub ahead of print. PMID: 35249272; PMCID: PMC8908811.
4. Dorabawila V, Hoefer D, Bauer UE, Bassett MT, Lutterloh E, Rosenberg ES. Effectiveness of the BNT162b2 vaccine among children 5-11 and 12-17 years in New York after the Emergence of the Omicron Variant. medRxiv 2022.02.25.22271454; doi: https://doi.org/10.1101/2022.02.25.22271454
5. Hause AM, Gee J, Baggs J, et al. COVID-19 Vaccine Safety in Adolescents Aged 12-17 Years - United States, December 14, 2020-July 16, 2021. MMWR Morb Mortal Wkly Rep. 2021 Aug 6;70(31):1053-1058. doi: 10.15585/mmwr.mm7031e1. PMID: 34351881; PMCID: PMC8367318.