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

  1. Santiago Romero-Brufau
  2. Ayush Chopra
  3. Alex J Ryu
  4. Esma Gel
  5. Ramesh Raskar
  6. Walter Kremers
  7. Karen S Anderson
  8. Jayakumar Subramanian
  9. Balaji Krishnamurthy
  10. Abhishek Singh
  11. Kalyan Pasupathy
  12. Yue Dong
  13. John C O’Horo
  14. Walter R Wilson
  15. Oscar Mitchell
  16. Thomas C Kingsley

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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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  3. Version published to 10.1136/bmj.n1087
  4. ScreenIT

    SciScore for 10.1101/2021.02.23.21252299: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We used Python 3.7, the full list of packages can be found in the supplemental material.
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We identified three primary limitations of our study design: (1) the paucity of clinical trial data regarding first dose vaccine efficacy, (2) information on immune decay in first dose only recipients, and (3) whether the vaccine is sterilizing or not. Our study did not measure the impact of COVID-19 mutant strains and various infectivity rate, or differences in behavior geographically, or the impact of other preventative measures such as digital exposure notification or testing availability and turn-around-times that are variable state-to-state[22]. These are limitations but would not likely change the relative differences measured between strategies. In the BNT162b2 and mRNA-1273 vaccine trials, the single dose vaccine efficacy was initially reported to be 52% and 80%, respectively. This was estimated in the small subset of subjects who did not receive the second dose during the trial [2, 3, 23]. Since these were not defined study sub-groups the advantages of randomization in preventing bias cannot be assumed to hold true, and in fact unknown bias in these individuals is likely. This limitation cannot be overcome using simulation modeling. However, we believe reasonable estimates can be made using the data available. The 52% vaccine efficacy in the Pfizer study was attributed to inclusion of the first 12 days after vaccination in their estimate. Using the 12 days underestimates the true vaccine efficacy because sufficient time to develop immunity had not occurred. This is w...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  5. Version published to 10.1101/2021.02.23.21252299v1 on medRxiv