What is the decline in the effectiveness of Covid-19 vaccines and the consequences on mortality ?

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As COVID-19 breakthrough infections continue to emerge in some vaccine recipients and health authorities are developing policies around booster vaccinations, national data on COVID-19 vaccine breakthrough infections is inadequate but urgently needed.

Now a study from the Public Health Institute, the Veterans Affairs Medical Center and the University of Texas Health Science Center, published today in the journal Science, has analyzed COVID infection by vaccination status among 780,225 Veterans.

Researchers found that protection against any COVID-19 infection declined for all vaccine types, with overall vaccine protection declining from 87.9% in February to 48.1% by October 2021.

  • The decline was greatest for the Janssen (Johnson & Johnson) vaccine, with protection against infection declining from 86.4% in March to 13.1% in September
  • Declines for PfizerBioNTech were from 86.9% to 43.3%
  • Declines for Moderna were 89.2% to 58%.

While most previous studies have focused on the PfizerBioNTech or Moderna vaccines, the Science study is the first to compare protection declines across the three main vaccine types, and the first to show the comparably dramatic decline in effectiveness for the Janssen vaccine.

Declines were assessed over the period February 1, 2021 to October 1, 2021, reflecting the emergence and dominance of the Delta variant in the U.S. Patterns of breakthrough infection over time were consistent by age, despite rolling vaccine eligibility, implicating the Delta variant as the primary determinant of infection.

Importantly, vaccination of any type was protective against death among individuals who did become infected. The relative benefit of vaccination for protection against death was greater for persons under 65 but was also very strong for persons over 65.

The study showed that the risk of death from COVID infection was highest in unvaccinated Veterans, regardless of age and comorbidities.

While some breakthrough infections resulted in death, vaccination remained protective against death in those who became infected during the Delta surge.

For those under 65 years old, vaccines overall were 81.7% effective against death.

  • Protection against death was greatest for the Pfizer vaccine, at 84.3%.
  • Moderna was the next most effective, at 81.5%.
  • Janssen was 73% effective.

For those 65 and over, overall vaccine effectiveness against death was 71.6%.

  • Moderna was 75.5% effective.
  • Pfizer was 70.1% effective.
  • Janssen was 52.2% effective.

“Our study gives researchers, policy makers and others a strong basis for comparing the long-term effectiveness of COVID vaccines, and a lens for making informed decisions around primary vaccination, booster shots, and other multiple layers of protection, including masking mandates, social distancing, testing and other public health interventions to reduce chance of spread,” said Dr. Barbara Cohn of PHI, the lead author of the study. “For example, the CDC recommendation for boosters for all Janssen recipients over 18 is supported by our results.

And, given the declines in vaccine protection and the dominance of the more infective Delta variant, we urge swift action to promote primary vaccination, boosters and to also encourage masking, social distancing and other layers of protection against infection.

This is supported by our finding that breakthrough infections are not benign, but also by the strong evidence that vaccination still protects against death even for persons with breakthrough infections, compared to persons who become infected and are not vaccinated.”

The FDA authorized Pfizer boosters for some groups in September and Moderna and Janssen boosters in October, and the CDC has made similar recommendations, including supporting a “mix and match” approach that allows people to choose any of the three vaccine boosters regardless of which they were given initially.


Over the past several months, there has been fierce debate in the public domain as to whether booster vaccinations are needed to sustain vaccine-induced immunological protection against SARS-CoV-2 infection.1 Discussions in medical journals, news outlets, social media, and among the wider public have been robust but limited owing to the paucity of data for the breadth and durability of existing vaccines.

In The Lancet, Sara Tartof and colleagues from Kaiser Permanente Southern California (KPSC) and Pfizer provide evidence that supports the use of a third vaccination for those who completed an initial series, administered at least 7 days apart, with the BNT162b2 (tozinameran, Pfizer–BioNTech) mRNA COVID-19 vaccine.2

With the spike in cases across the globe owing to the delta (B.1.617.2) variant of SARS-CoV-2, increasing numbers of so-called breakthrough infections have occurred among vaccinated individuals.3, 4 The question emerging is whether the breakthrough cases are due to waning immunity, in which case a booster is required, or simply incomplete coverage of the delta variant by vaccine-induced immunity.

Tartof and colleagues reviewed medical records in the KPSC health-care system, and found that among 3 436 957 individuals included, 1 146 768 received at least one dose of the vaccine, 91·0% of whom were fully vaccinated.2 The remaining unvaccinated individuals served as control participants. Vaccine effectiveness was estimated at monthly intervals after achieving fully vaccinated 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 a Pacific Islander, and 8·0% were Black. In the year before the study start date, 74 284 (2·2%) had a positive SARS-CoV-2 PCR test.2

Over the entire study period, the vaccine was 73% (95% CI 72–74) effective against infection among fully vaccinated people. However, the effectiveness against infections was highest during the first month after full vaccination (88% [86–89]), falling to 47% (43–51) after 5 months.

Effectiveness against delta variant infections was similarly high during the first month after full vaccination (93% [85–97]), declining to 53% (39–65) effectiveness at 4 months after completion of the initial vaccine series.

Similar declines in vaccine effectiveness were observed with non-delta variants. Fortunately, the protection against hospital admissions remained high at 93% (84–96) for delta and 95% (90–98) for non-delta variants throughout the 6-month observation period.

Taken together, these data support the narrative of waning vaccine-related immune protection over time against SARS-CoV-2 infection, regardless of variant, thereby supporting the potential benefit of a booster injection 6–8 months after completion of the initial BNT162b2 vaccine series.

The strengths of this study include its large sample size, ability to evaluate a subset of individuals who were infected with delta and other variants, and continuous assessment of vaccine status, incident SARS-CoV-2 infection, and hospital admissions.

The limitations include inability to establish a causal relationship between vaccinations and outcomes owing to the retrospective nature of the study, absence of randomisation, channelling bias (ie, tendency for clinicians to prescribe treatment based on a patient’s prognosis), and the likelihood that some individuals were diagnosed with COVID-19 or received vaccination outside of the KPSC system.

A key missed opportunity is the absence of assessment of those who had previous COVID-19 and the effect of vaccination, or no vaccination, on a recurrent episode of infection.

Despite the contributions of this Article, many questions remain unanswered. Is immunity more robust for those who had a longer (eg, 3 month) gap between vaccinations? What about the need for a third vaccination among those who received the mRNA-1273 (Moderna) vaccine series or a second vaccination for those who received the Ad26.COV2.S (Janssen) vaccine?

Is mixing and matching vaccine products (eg, BNT162b2 followed by mRNA-1273) beneficial and safe?

Does this immunity wane in a similar manner as the vaccine for those who have had COVID-19 previously?

Does vaccination after SARS-CoV-2 infection generate broader and more durable immunity?

Or do these individuals, too, need a booster?

With preservation of protection against severe disease and hospital admissions, should vaccine distribution be prioritised to resource-constrained regions before commitment to a third vaccination for people who are immunocompetent?

The reason so many questions exist is simple: the rapid release of the vaccines, which is estimated to have saved more than 100 000 lives in the USA during the first 5 months,5 did not allow collection of durability data.

We are learning as we go. Studies like Tartof and colleagues’ study provide essential insights into the nature of immune protection induced by COVID-19 vaccines that can inform public policy.

Yet, data from one study are not sufficient to answer the remaining questions.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516399/


More information: Barbara A. Cohn et al, SARS-CoV-2 vaccine protection and deaths among US veterans during 2021, Science (2021). DOI: 10.1126/science.abm0620

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