Deaths averted by vaccination due to reduced transmission can exceed those from direct protection of vaccinated individuals for SARS-CoV-2

  1. Billy J. Gardner
  2. A. Marm Kilpatrick

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Abstract

Vaccination programs often focus on direct protection of vaccinated individuals against disease and discount reductions in transmission, which can result in preventable disease and death. Initial clinical trials for most COVID-19 vaccines only measured direct protection, and dosing and vaccine selection decisions have, so far, ignored effects on transmission. Here we provide a novel empirical framework for incorporating effects of COVID-19 vaccination on transmission in a continuous dynamic immune landscape. We quantified relationships between neutralizing antibody titers and vaccine effectiveness for both susceptibility (VE S ) and infectiousness (VE I ) and quantified changes in VE with waning and boosting of immunity. We used these relationships to quantify the impact that additional doses of mRNA vaccines (BNT162b2 and mRNA-1273) could have had in reducing transmission and deaths caused by the deadliest SARS-CoV-2 variant, Delta, in Autumn 2021. Neutralizing antibodies waned 8-fold in 2021 over the six months following initial vaccination with mRNA vaccines, which reduced VE S 33-38% (from 75-81% to 47-54%) and VE I 62-65% (from 47-57% to 16-22%) against the Delta variant. Third doses increased neutralizing antibody titers 13-26-fold, which more than restored VE and reduced the relative risk of transmission 7-10-fold. Administering third doses by September 1, 2021, could have reduced the effective reproductive number R t by 19%, stopped surges in transmission in many populations, and averted an estimated 113,000 deaths in the United States, which is 2.6-12.4 fold higher than direct effects in vaccinated individuals. Vaccination programs that incorporate effects on transmission in trial design, vaccination frequency, and vaccine choice are needed to address current and future public health challenges.

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  1. Version published to 10.1101/2021.10.25.21265500v5 on medRxiv
  2. Version published to 10.1101/2021.10.25.21265500v4 on medRxiv
  3. Version published to 10.1101/2021.10.25.21265500v3 on medRxiv
  4. Version published to 10.1101/2021.10.25.21265500v2 on medRxiv
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    SciScore for 10.1101/2021.10.25.21265500: (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

    Antibodies
    SentencesResources
    We calculated 95% CIs for predicted values of Rt that incorporated uncertainty in the relationships between neutralizing antibody titers and protection against infection and transmission (Figures 1 and S4).
    S4
    suggested: None

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

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has several limitations. First and foremost is the reliance on neutralizing antibody titers as a predictor of protection against infection and transmission. Although the analyses here, and elsewhere suggest a strong relationship between neutralizing antibody titers and protection at the population level [3, 17] and individual level [32], other parts of the immune system, such as T-cells, also play key roles in protection from infection and disease. Second, our analyses use population averages for estimates of protection against infection and transmission and ignore age-specific variation among individuals (as well as other factors). Third, the data available to estimate vaccine protection against all infections was very limited and we are unaware of any studies that have estimated the full impact of vaccination against transmission given infection from the Delta variant. Finally, we assume well-mixed populations in calculating reductions in the reproductive number Rt. Clearly a targeted vaccination approach would be more effective than that outlined here if individuals that were highly connected to at-risk individuals could be targeted for third doses [33]. Finally, we focused on third dose boosters using the Pfizer vaccine, but third doses for other vaccines, including heterologous boosting [34], have also recently been approved in the USA and elsewhere. In summary, many countries have already begun to deploy third doses to protect at-risk individuals, and some cou...

    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.

    Results from scite Reference Check: We found no unreliable references.

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  6. Version published to 10.1101/2021.10.25.21265500v1 on medRxiv