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Comparative Study
. 2021 May 12:373:n1087.
doi: 10.1136/bmj.n1087.

Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study

Santiago Romero-Brufau  1   2 , Ayush Chopra  3 , Alex J Ryu  1 , Esma Gel  4 , Ramesh Raskar  3 , Walter Kremers  5 , Karen S Anderson  4 , Jayakumar Subramanian  6 , Balaji Krishnamurthy  6 , Abhishek Singh  3 , Kalyan Pasupathy  5 , Yue Dong  7 , John C O'Horo  1 , Walter R Wilson  1 , Oscar Mitchell  8 , Thomas C Kingsley  9
Affiliations
Comparative Study

Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study

Santiago Romero-Brufau et al. BMJ. .

Erratum in

Abstract

Objective: To estimate population health outcomes with delayed second dose versus standard schedule of SARS-CoV-2 mRNA vaccination.

Design: Simulation agent based modeling study.

Setting: Simulated population based on real world US county.

Participants: The simulation included 100 000 agents, with a representative distribution of demographics and occupations. Networks of contacts were established to simulate potentially infectious interactions though occupation, household, and random interactions.

Interventions: Simulation of standard covid-19 vaccination versus delayed second dose vaccination prioritizing the first dose. The simulation runs were replicated 10 times. Sensitivity analyses included first dose vaccine efficacy of 50%, 60%, 70%, 80%, and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread (that is, non-sterilizing vaccine); and an alternative vaccination strategy that implements delayed second dose for people under 65 years of age, but not until all those above this age have been vaccinated.

Main outcome measures: Cumulative covid-19 mortality, cumulative SARS-CoV-2 infections, and cumulative hospital admissions due to covid-19 over 180 days.

Results: Over all simulation replications, the median cumulative mortality per 100 000 for standard dosing versus delayed second dose was 226 v 179, 233 v 207, and 235 v 236 for 90%, 80%, and 70% first dose efficacy, respectively. The delayed second dose strategy was optimal for vaccine efficacies at or above 80% and vaccination rates at or below 0.3% of the population per day, under both sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100 000. The delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested.

Conclusions: A delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Comparison of cumulative mortality for delayed second dose versus standard vaccination strategy under four different first dose effectiveness assumptions. Results are shown for a vaccination rate of 0.3% of the population per day. The total cumulative mortality on day 180 is lower for the delayed second dose scenario under the assumption that the first dose effectiveness is ≥80%
Fig 2
Fig 2
Comparison of cumulative number of infections and hospital admissions for delayed second dose versus standard vaccination strategy under four different first dose effectiveness assumptions. Results are shown for a vaccination rate of 0.3% of the population per day. The cumulative number of infections on day 180 is lower for the delayed second dose approach. The peak hospital census becomes similar for both approaches as the efficacy of the first dose of vaccine is reduced
Fig 3
Fig 3
Comparison of cumulative mortality for delayed second dose versus standard vaccination strategy under three different vaccination rate assumptions. The comparative effectiveness of double dose on schedule and delayed second dose strategies is dependent on vaccination rate. For a vaccination rate of 1% of the population per day, the standard strategy seems to be superior. For a vaccination rates of 0.3% or lower, the delayed second dose strategy results in a lower cumulative mortality
Fig 4
Fig 4
Comparison of cumulative mortality for three different vaccination strategies (delayed second dose versus standard vaccination versus delayed second dose except for 65+) under three different vaccination rate assumptions. The “delayed second dose except for 65+” (pink line) strategy seems optimal or close to optimal under all three assumptions, making it a safe choice in the face of an uncertain future vaccination rate
Fig 5
Fig 5
Cumulative mortality for delayed second dose versus standard dosing under a non-sterilizing vaccine assumption. The results are similar to those under a sterilizing vaccine assumption: the delayed second dose strategy seems optimal for a first dose efficacy of ≥80%
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References

    1. Sharma O, Sultan AA, Ding H, Triggle CR. A Review of the Progress and Challenges of Developing a Vaccine for COVID-19. Front Immunol 2020;11:585354. 10.3389/fimmu.2020.585354 - DOI - PMC - PubMed
    1. Polack FP, Thomas SJ, Kitchin N, et al. C4591001 Clinical Trial Group . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2020;383:2603-15. 10.1056/NEJMoa2034577 - DOI - PMC - PubMed
    1. Baden LR, El Sahly HM, Essink B, et al. COVE Study Group . Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 2021;384:403-16. 10.1056/NEJMoa2035389 - DOI - PMC - PubMed
    1. Voysey M, Clemens SAC, Madhi SA, et al. Oxford COVID Vaccine Trial Group . Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111. 10.1016/S0140-6736(20)32661-1 - DOI - PMC - PubMed
    1. A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants (ENSEMBLE). 2021 https://clinicaltrials.gov/ct2/show/NCT04505722.

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