Develop an incremental COVID-19 vaccination policy


Over the past few months, there has been fierce debate in the public domain as to whether booster vaccinations are necessary to maintain vaccine-induced immunological protection against SARS-CoV-2 infection.
1
COVID-19 booster vaccines: what we know and who does what.

Discussions in medical journals, media, social media and the general public have been strong but limited due to the lack of data on the extent and durability of existing vaccines.

In The Lancet, Sara Tartof and her colleagues at Kaiser Permanente Southern California (KPSC) and Pfizer provide evidence that supports the use of a third vaccination for those who have completed an initial series, administered at least 7 days apart, with the BNT162b2 (tozinameran, Pfizer-BioNTech) COVID-19 mRNA vaccine.
2
  • Tartof SY
  • Slezak JM
  • Fischer H
  • et al.
Efficacy of BNT162b2 COVID-19 mRNA vaccine for up to 6 months in a large integrated healthcare system in the United States: a retrospective cohort study.

With the increase in the number of cases around the world due to the delta variant (B.1.617.2) of SARS-CoV-2, an increasing number of so-called “breakthrough” infections have occurred in those vaccinated.

3
  • Hacisuleyman E
  • Hale C
  • Saito Y
  • et al.
Revolutionary vaccine infections with variants of SARS-CoV-2.

,

4
  • Brown CM
  • Vostok J
  • Johnson H
  • et al.
Outbreak of SARS-CoV-2 infections, including COVID-19 virus infections, associated with large public gatherings – Barstable County, Massachusetts, July 2021.

The question is whether the breakthrough cases are due to waning immunity, in which case a booster is needed, or simply incomplete coverage of the delta variant by vaccine-induced immunity.

Tartof and his colleagues reviewed the medical records of the KPSC health system and found that of 3,436,957 people included, 1,146,768 received at least one dose of the vaccine, of which 91.0% were fully immunized.
2
  • Tartof SY
  • Slezak JM
  • Fischer H
  • et al.
Efficacy of BNT162b2 COVID-19 mRNA vaccine for up to 6 months in a large integrated healthcare system in the United States: a retrospective cohort study.

The other unvaccinated individuals served as control participants. Vaccine efficacy was assessed at one month intervals after reaching fully immunized status. The distribution of participants was balanced between groups, with a median age of 45 years (IQR 29-61); 1,799,395 (52.4%) participants were female and 1,637,394 (47.6%) were male; 40.5% were Hispanic, 32.3% were white, 11.6% were Asian or Pacific Islander, and 8.0% were black. In the year before the start date of the study, 74,284 (2.2%) had a positive SARS-CoV-2 PCR test.

2
  • Tartof SY
  • Slezak JM
  • Fischer H
  • et al.
Efficacy of BNT162b2 COVID-19 mRNA vaccine for up to 6 months in a large integrated healthcare system in the United States: a retrospective cohort study.

Over the entire study period, the vaccine was 73% effective (95% CI 72-74) against infection in fully vaccinated individuals. However, efficacy against infections was highest during the first month after full vaccination (88% [86–89]), dropping to 47% (43-51) after 5 months. Efficacy against delta variant infections was equally high during the first month after full vaccination (93% [85–97]), decreasing to 53% (39-65) efficacy at 4 months after the end of the initial vaccination series. Similar decreases in vaccine efficacy were seen with the non-delta variants. Fortunately, protection from hospitalizations remained high at 93% (84-96) for delta variants and 95% (90-98) for non-delta variants throughout the 6-month observation period. Taken together, these data support the narrative of decreased vaccine-related immune protection over time against SARS-CoV-2 infection, regardless of the variant, thus supporting the potential benefit of an injection of booster 6 to 8 months after the end of the initial series of BNT162b2 vaccines.

The strengths of this study include its large sample size, its ability to assess a subset of individuals infected with delta and other variants, and the continuous assessment of vaccination status, from incident infection to. SARS-CoV-2 and hospitalizations. Limitations include the inability to establish a causal relationship between vaccinations and outcomes due to the retrospective nature of the study, lack of randomization, channel bias (i.e. trend of clinicians to prescribe treatment based on a patient’s prognosis) and the likelihood that some people have been diagnosed with COVID-19 or received a vaccination outside of the KPSC system. A key missed opportunity is the failure to assess those who have already had COVID-19 and the effect of vaccination, or lack of vaccination, on a recurrent episode of infection.

Despite the contributions of this article, many questions remain unanswered. Is immunity more robust for those who have had a longer interval (eg, 3 months) between vaccinations? What about the need for a third vaccination in those who received the mRNA-1273 vaccine series (Moderna) or a second vaccination for those who received the Ad26.COV2.S vaccine (Janssen)? Is mixing and pairing of vaccine products (eg, BNT162b2 followed by mRNA-1273) beneficial and safe? Does this immunity decrease in the same way as the vaccine for those who have already had COVID-19? Does vaccination after infection with SARS-CoV-2 generate broader and longer-lasting immunity? Or do these people also need a reminder? With the preservation of protection against serious illness and hospitalizations, should vaccine distribution be a priority in resource-limited areas before committing to a third vaccination for immunocompetent people?

The reason why so many questions exist is simple: the rapid release of the vaccines, which is said to have saved over 100,000 lives in the US in the first 5 months,
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  • Gupta S
  • Singer J
  • Simon KI
  • et al.
COVID-19 vaccinations could have prevented up to 140,000 deaths in the United States.

did not allow collection of sustainability data. We learn as we go. Studies such as the study by Tartof and colleagues provide essential information on the nature of the immune protection induced by COVID-19 vaccines that can inform public policy. Yet data from one study is not sufficient to answer the remaining questions.

I do not declare any competing interests.

The references

  1. 1.

    COVID-19 booster vaccines: what we know and who does what.

    BMJ. 2021; 374: n2082

  2. 2.
    • Tartof SY
    • Slezak JM
    • Fischer H
    • et al.

    Efficacy of BNT162b2 COVID-19 mRNA vaccine for up to 6 months in a large integrated healthcare system in the United States: a retrospective cohort study.

    Lancet. 2021; 398: 1407-1416

  3. 3.
    • Hacisuleyman E
    • Hale C
    • Saito Y
    • et al.

    Revolutionary vaccine infections with variants of SARS-CoV-2.

    N Engl J Med. 2021; 384: 2212-2218

  4. 4.
    • Brown CM
    • Vostok J
    • Johnson H
    • et al.

    Outbreak of SARS-CoV-2 infections, including COVID-19 virus infections, associated with large public gatherings – Barstable County, Massachusetts, July 2021.

    MMWR Morb Mortal Wkly Rep. 2021; 70: 1059-1062

  5. 5.
    • Gupta S
    • Singer J
    • Simon KI
    • et al.

    COVID-19 vaccinations could have prevented up to 140,000 deaths in the United States.

    Health Aff. 2021; 40: 1465-1472

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