Evaluating the Impact of Extended Dosing Intervals on MRNA COVID-19 Vaccine Effectiveness in Adolescents

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2024 Sep 12

PMID 39267060

Authors

Tim K Tsang

Sheena G Sullivan

Yu Meng

Francisco Tsz Tsun Lai

Min Fan

Xiaotong Huang

Yun Lin

Liping Peng

Chengyao Zhang

Bingyi Yang

Kylie E C Ainslie

Benjamin J Cowling

Affiliations

Soon will be listed here.

Abstract

Background: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose.

Methods: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches.

Results: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose.

Conclusions: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

References

Yang B, Huang X, Gao H, Leung N, Tsang T, Cowling B . Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis. BMC Med. 2022; 20(1):409. PMC: 9595080. DOI: 10.1186/s12916-022-02600-0. View

Florentino P, Millington T, Cerqueira-Silva T, Robertson C, Oliveira V, Junior J . Vaccine effectiveness of two-dose BNT162b2 against symptomatic and severe COVID-19 among adolescents in Brazil and Scotland over time: a test-negative case-control study. Lancet Infect Dis. 2022; 22(11):1577-1586. PMC: 9359673. DOI: 10.1016/S1473-3099(22)00451-0. View

Hall V, Ferreira V, Wood H, Ierullo M, Majchrzak-Kita B, Manguiat K . Delayed-interval BNT162b2 mRNA COVID-19 vaccination enhances humoral immunity and induces robust T cell responses. Nat Immunol. 2022; 23(3):380-385. DOI: 10.1038/s41590-021-01126-6. View

Xie R, Edwards K, Adam D, Leung K, Tsang T, Gurung S . Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong. Nat Commun. 2023; 14(1):2422. PMC: 10134727. DOI: 10.1038/s41467-023-38201-5. View

Chantasrisawad N, Techasaensiri C, Kosalaraksa P, Phongsamart W, Tangsathapornpong A, Jaru-Ampornpan P . The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial. Int J Infect Dis. 2023; 130:52-59. PMC: 10011807. DOI: 10.1016/j.ijid.2023.02.017. View

Kahn F, Bonander C, Moghaddassi M, Christiansen C, Bennet L, Malmqvist U . Previous SARS-CoV-2 infections and their impact on the protection from reinfection during the Omicron BA.5 wave - a nested case-control study among vaccinated adults in Sweden. IJID Reg. 2024; 10:235-239. PMC: 10964055. DOI: 10.1016/j.ijregi.2024.02.004. View

Pouwels K, Pritchard E, Matthews P, Stoesser N, Eyre D, Vihta K . Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. Nat Med. 2021; 27(12):2127-2135. PMC: 8674129. DOI: 10.1038/s41591-021-01548-7. View

Khan F, Nguyen J, Singh T, Puzniak L, Wiemken T, Schrecker J . Estimated BNT162b2 Vaccine Effectiveness Against Infection With Delta and Omicron Variants Among US Children 5 to 11 Years of Age. JAMA Netw Open. 2022; 5(12):e2246915. PMC: 9856252. DOI: 10.1001/jamanetworkopen.2022.46915. View

Mefsin Y, Chen D, Bond H, Lin Y, Cheung J, Wong J . Epidemiology of Infections with SARS-CoV-2 Omicron BA.2 Variant, Hong Kong, January-March 2022. Emerg Infect Dis. 2022; 28(9):1856-1858. PMC: 9423929. DOI: 10.3201/eid2809.220613. View

10.

Diaz G, Parsons G, Gering S, Meier A, Hutchinson I, Robicsek A . Myocarditis and Pericarditis After Vaccination for COVID-19. JAMA. 2021; 326(12):1210-1212. PMC: 8340007. DOI: 10.1001/jama.2021.13443. View

11.

Westreich D, Cole S . Invited commentary: positivity in practice. Am J Epidemiol. 2010; 171(6):674-7. PMC: 2877454. DOI: 10.1093/aje/kwp436. View

12.

El Adam S, Zou M, Kim S, Henry B, Krajden M, Skowronski D . SARS-CoV-2 mRNA Vaccine Effectiveness in Health Care Workers by Dosing Interval and Time Since Vaccination: Test-Negative Design, British Columbia, Canada. Open Forum Infect Dis. 2022; 9(5):ofac178. PMC: 9047244. DOI: 10.1093/ofid/ofac178. View

13.

McMenamin M, Nealon J, Lin Y, Wong J, Cheung J, Lau E . Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study. Lancet Infect Dis. 2022; 22(10):1435-1443. PMC: 9286709. DOI: 10.1016/S1473-3099(22)00345-0. View

14.

Ferdinands J, Rao S, Dixon B, Mitchell P, DeSilva M, Irving S . Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study. BMJ. 2022; 379:e072141. PMC: 9527398. DOI: 10.1136/bmj-2022-072141. View

15.

Fleming-Dutra K, Britton A, Shang N, Derado G, Link-Gelles R, Accorsi E . Association of Prior BNT162b2 COVID-19 Vaccination With Symptomatic SARS-CoV-2 Infection in Children and Adolescents During Omicron Predominance. JAMA. 2022; 327(22):2210-2219. PMC: 9107063. DOI: 10.1001/jama.2022.7493. View

16.

Amirthalingam G, Lopez Bernal J, Andrews N, Whitaker H, Gower C, Stowe J . Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England. Nat Commun. 2021; 12(1):7217. PMC: 8664823. DOI: 10.1038/s41467-021-27410-5. View

17.

Imai N, Rawson T, Knock E, Sonabend R, Elmaci Y, Perez-Guzman P . Quantifying the effect of delaying the second COVID-19 vaccine dose in England: a mathematical modelling study. Lancet Public Health. 2023; 8(3):e174-e183. PMC: 9910835. DOI: 10.1016/S2468-2667(22)00337-1. View

18.

Ray G, Lewis N, Klein N, Daley M, Lipsitch M, Fireman B . Depletion-of-susceptibles Bias in Analyses of Intra-season Waning of Influenza Vaccine Effectiveness. Clin Infect Dis. 2019; 70(7):1484-1486. PMC: 7318775. DOI: 10.1093/cid/ciz706. View

19.

Tsang T, Wang C, Yang B, Cauchemez S, Cowling B . Using secondary cases to characterize the severity of an emerging or re-emerging infection. Nat Commun. 2021; 12(1):6372. PMC: 8569220. DOI: 10.1038/s41467-021-26709-7. View

20.

Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E . Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N Engl J Med. 2022; 386(16):1532-1546. PMC: 8908811. DOI: 10.1056/NEJMoa2119451. View