Group of 18 Experts
EXPERTS WEIGH IN ON BOOSTER SHOTS: The experts who authored The Lancet article on vaccine boosters published September 13, 2021: Marion Gruber; Philip Krause; Soumya Swaminathan; Ana-Maria Henao-Restrepo; Mike Ryan; Thomas R Fleming; Richard Peto; Ira M Longini; J Peter Figueroa; Jonathan A C Sterne; Alejandro Cravioto; Helen Rees; Julian P T Higgins; Isabelle Boutron; Hongchao Pan; Narendra Arora; Fatema Kazi; and Rogerio Gaspar. Image Credit: The Lancet, WHO, LinkedIn, Gulf News

Highlights

  • Vaccines work incredibly well against COVID-19, and all known variants, say experts citing observational studies.
  • Booster shots may not be warranted across the board among the already fully-vaccinated people; they would be of better use to jab the unvaccinated first.
  • Reports of “breakthrough” cases, i.e. people getting infected with COVID-19 despite prior vaccination, hog social media.
  • It’s a little-understood phenomenon and the occurrence is quite rare — from 0.008% to 0.01%  — data from US, Israeli & British studies show.

Current vaccines demonstrate an impressive level of efficacy against COVID-19. They work so well, that the use of boosters for all may not be warranted at this point, say a group of experts. Screaming reports about a rather small number of "breakthrough” infections, though statistically insignificant, tend to cloud that fact.

An article co-authored by 18 experts and published September 13, 2021 in The Lancet cited current observational studies showing vaccines have upwards of 90% efficacy. The 18-member expert group was led by Philip Krause of the Food and Drug Administration (FDA), Prof. Thomas Fleming of the University of Washington, Soumya Swaminathan, Michael Ryan and Fatema Kazi, of the WHO.

What experts say:

Are current vaccines effective against variants?

Yes. Following are the key point the experts’ group highlighted:

  1. Current vaccines are impressively effective, conferring a high average of effectiveness against severe disease by known variants, including the highly-infectious Delta.
  2. For the unvaccinated, the flip-side is true: they account for the great majority of hospitalisations and deaths. “Even in populations with fairly high vaccination rates, the unvaccinated are still the major drivers of transmission and are themselves at the highest risk of serious disease.”
  3. In countries with high vaccination rates, it’s the people who are unvaccinated who are driving up COVID-19 transmission — and who are at highest risk of becoming very ill.

Given the infectious variants, what is the efficacy of vaccines?

No vaccine is 100% effective. However, the group cited that vaccine effectiveness (VE) at the present two-dose reign remains high — an average of 95% VE against severe disease, including the Delta variant. Vaccination was also more than 80% effective at preventing any infection.

95%

Vaccine efficacy against severe disease, including the Delta variant, according to the Group of 18 experts who published their article in The Lancet, September 13, 2021.

Are boosters needed now?

This is a major point of contention among the health experts.

The first camp, represented by Krause-Fleming-led team who published their viewpoint in The Lancet, argues that boosters are not yet needed as of the moment — as vaccines are working well.

Their main point: current vaccines are best used to immunise the unvaccinated. The group also argues that booster should be antigen-specific: “The effectiveness of boosting against the main variants now circulating and against even newer variants could be greater and longer-lived if the booster vaccine antigen is devised to match the main circulating variants.”

White House task force Fauci
White House coronavirus task force members, including Dr Anthony Fauci of the National Institutes of Health, White House coronavirus coordinator Dr Deborah Birx, Centers for Disease Control (CDC) Director Robert Redfield and US Surgeon General Jerome Adams listen to President Donald Trump during the daily coronavirus disease (COVID-19) briefing at the White House in Washington, US, April 22, 2020. Image Credit: Reuters

The second camp — made up of CDC Director Rochelle Walensky, US chief infectious disease expert Anthony Fauci (National Institutes of Allergy and Infectious Diseases), and FDA Acting Commissioner Janet Woodcock — are top medical advisers to US President Joe Biden, who announced his booster programme in the US.

Walensky CDC chief
File Photo taken on January 12, 2021: Dr. Rochelle P. Walensky speaks in the presence of US President-elect Joseph R. Biden Jr. She was Biden’s nominee to lead the Centers for Disease Control and Prevention (CDC). Image Credit: New York Times.

Who are the scientists who conducted the review?

Group of 18 Experts
THE GROUP OF 18: The experts who authored The Lancet article on vaccine boosters published September 13, 2021: Marion Gruber; Philip Krause; Soumya Swaminathan; Ana-Maria Henao-Restrepo; Mike Ryan; Thomas R Fleming; Richard Peto; Ira M Longini; J Peter Figueroa; Jonathan A C Sterne; Alejandro Cravioto; Helen Rees; Julian P T Higgins; Isabelle Boutron; Hongchao Pan; Narendra Arora; Fatema Kazi; and Rogerio Gaspar.

The Lancet listed the authors as:

  • Marion Gruber, head of the Office of Vaccines Research and Review, US Food and Drug Administration
  • Philip Krause, deputy head of the Office of Vaccines Research and Review, US Food and Drug Administration
  • Soumya Swaminathan, Chief Scientist of the World Health Organisation (WHO)
  • Ana-Maria Henao-Restrepo, Head of the Research and Development Unit at WHO.
  • Mike Ryan, Dr Mike Ryan, Head of Emergency Programmes, WHO.
  • Prof Thomas R Fleming
  • Prof Richard Peto, FRS
  • Prof Ira M Longini, PhD
  • Prof J Peter Figueroa, PhD
  • Prof Jonathan A C Sterne, PhD
  • Alejandro Cravioto, PhD
  • Prof Helen Rees, MD
  • Prof Julian P T Higgins, PhD
  • Prof Isabelle Boutron, PhD
  • Prof Hongchao Pan, PhD
  • Prof Narendra Arora, MD
  • Fatema Kazi, PhD
  • Rogerio Gaspar, PhD

What’s the main point of the expert group?

The group argued that, at the moment, immunising those who haven’t gotten any shots yet would make more sense, instead of giving the shots as “boosters” to already-vaccinated people, especially in the US, whose people have easier access to vaccine production facilities.

They argue it’s better to give the jabs to those who live in places with little access to the jabs.

Are there risks with giving multiple or frequent boosters?

The group did cite the risks of early or multiple dosing of boosters: “There could be risks if boosters are widely introduced too soon, or too frequently — especially with vaccines that can have immune-mediated side-effects (such as myocarditis, which is more common after the second dose of some mRNA vaccines, or Guillain-Barre syndrome, which has been associated with adenovirus-vectored COVID-19 vaccines),” the group wrote.

“Even if boosting were eventually shown to decrease the medium-term risk of serious disease, current vaccine supplies could save more lives if used in previously unvaccinated populations,” the authors wrote.

Is the group rejecting booster shots altogether?

No. The group stated booster shots may be needed for the general population — but at a later time, depending on certain conditions and if clinical data show a definitive wane in immunity or variants with new antigens (i.e. they have evolved further) are found.

They wrote: “Boosting might ultimately be needed in the general population because of waning immunity to the primary vaccination or because variants expressing new antigens have evolved to the point at which immune responses to the original vaccine antigens no longer protect adequately against currently circulating viruses.”

Two of the authors, Gruber and Krause, have resigned from the FDA last week and have said they would step down later this year; they were two of a group of FDA staff who last year pushed back against pressure by Trump to speed up the authorisation of the COVID vaccines.

Are “breakthrough” infections driving the current surge in COVID-19 cases?

No. So far, the data show infections are driven by unvaccinated people, rather than those who were infected after vaccination.

By implication, it shows vaccines work impressively well in curbing severe COVID cases that lead to hospitalisation and/or death.

Breakthrough infection
Breakthrough infection is defined as an illness in which a vaccinated individual becomes sick from the same illness that the vaccine is meant to prevent.

Reports about breakthrough infections, however, are often drummed up and interpreted as vaccine “failure”, which tends to receive a lot of attention, especially on social from the anti-vax camp.

What do studies shows about COVID-19 breakthrough cases?

A study in Israel found that severe COVID-19 breakthrough cases were mostly in older, sicker patients. This was based on 600 patients hospitalised with severe illness even if they received two doses of the Pfizer shot — a rare occurrence or 0.01% — of the 5.4 million fully vaccinated people then (August 2021).

About half (50%) of 600 hospitalised, fully-vaccinated patients were over the age of 60 or are immunocompromised.

0.01%

Percentage of hospitalisation among “breakthrough” cases in Israel in August (600 out of 5.4 million vaccinees).
israel30-1627631327510
An Israeli woman receives a third Pfizer-BioNTech COVID-19 vaccine in the Israeli city of Ramat HaSharon, Friday, July 30, 2021. Israel's prime minister on Thursday announced that the country would offer a coronavirus booster to people over 60 who have already been vaccinated. (AP Photo/Sebastian Scheiner) Image Credit: AP

In the US, more than 176 million people had been fully-vaccinated against COVID-19 as of September 7, 2021. Till then, CDC reported getting 14,115 patients with COVID-19 vaccine breakthrough infection who were hospitalised or died. That’s equivalent to a rate of 0.008%.

0.008%

rate of breakthrough infection in the US, as per CDC on September 7, 2021 (14,115 patients vs 176 million fully vaccinated)

Israel began offering booster shots to people age 60 and up in July. The US, citing data out of Israel and other findings, said it would make booster doses available to all Americans from September.

Also, a British study published in The Lancet on September 1, 2021 based on data from 1.24 million people (users of COVID Symptom Study app) found an extremely low rate of COVID-19 "breakthrough" infections, and even fewer symptoms in vaccinated people.

It’s one of the first large-scale, real-world data on how well vaccination protects people against catching a "breakthrough" COVID-19 infection, and how well it protects breakthrough patients from becoming seriously ill.

What do these numbers mean?

These are encouraging numbers: They show vaccines actually work. New, richer data are expected to come out in the coming days, which will help health policy makers and epidemiologists better understand of the true efficacy of three of the major vaccines — BNT162b2 from Pfizer–BioNTech), mRNA-1273 (from Moderna), and ChAdOx1 nCoV-19 (from Oxford–AstraZeneca) being used worldwide.

The US response — a booster shot for all — may be unwarranted at this point, say the experts.

US UN-1629363090077
A vaccination clinic at a Catholic Church in the Bronx borough of New York, Aug. 8, 2021. The Centers for Disease Control and Prevention released three studies on Aug. 18 as evidence that booster shots of the Pfizer-BioNTech and Moderna vaccines would be needed in the coming months. (James Estrin/The New York Times) Image Credit: NYT

Who are the people likely to get breakthrough COVID-19 cases?

Clinicians now see a trend: people with weakened immune systems are likely to get breakthrough cases. Dr John O’Horo, critical care and infectious disease specialist at Mayo Clinic (he did not take part in the expert’s paper), said breakthrough cases tend to cluster into immuno-compromised people: “We’re seeing that these breakthrough hospitalisations tend to happen in people we’d expect to have weaker immune system and might not have the same lasting protection from the vaccines.

When we look at where these breakthroughs that get hospitalised come from, they do fit into a few categories — all of which seem to point to having a weakened immune system, such as people who are transplant patients, who are on active chemotherapy and a few related illnesses.

- Dr John O’Horo, critical care and infectious disease specialist at Mayo Clinic

“When we look at where these breakthroughs that get hospitalised come from, they do fit into a few categories — all of which seem to point to having a weakened immune system, such as people who are transplant patients, who are on active chemotherapy and a few related illnesses.”

For the scientific community, the jury is still out on the full utility of a third shot for all. 

Several studies bear this out:

  1. In a study published September 7, 2021 in The Lancet, a research team led by Dr. Prerak V Juhani of the Department of Internal Medicine, Yale School of Medicine, noted rare emerging reports of severe COVID cases from breakthrough infections remains low.
  2. Results of an extensive Phase 3 trial with 30,420 volunteers published in the NEJM in December 30, 2020, showed the mRNA-1273 vaccine showed 94.1% efficacy at preventing COVID-19 illness, including severe disease (COVID-19 illness was confirmed in 185 participants in the placebo group vs 11 participants in the vaccine group).
  3. A smaller study conducted in Kentucky, USA published on the journal Morbidity and Mortality Weekly in April 2021 showed unvaccinated residents and health care personnel (HCP) had 3.0 and 4.1 times the risk of severe infection as did vaccinated residents and health care staff. It also found the vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective among health care professionals.
  4. The Krause-Flemming group who published their viewpoint in the Lancet on September 13, 2021, cited data which show the current vaccines do work. More important, the expert said data support the thesis that COVID variants have not developed an immune escape.

“The ability of vaccines that present the antigens of earlier phases of the pandemic (rather than variant-specific antigens) to elicit humoral immune responses against currently circulating variants, indicates that these variants have not yet evolved to the point at which they are likely to escape the memory immune responses induced by those vaccines,” they wrote.

“Even without any changes in vaccine efficacy, increasing success in delivering vaccines to large populations will inevitably lead to increasing numbers of breakthrough cases, especially if vaccination leads to behavioural changes in vaccinees.”

But tor the scientific community, the jury is still out. Not everyone is in agreement on the full utility of a third shot for all at this time. 

The US FDA booster documents
The US FDA booster documents on the Pfizer/BioNTech shot, a 53-page report, reviews all data on effectiveness (VE) vs infection. It show waning immunity not related to Delta is just a matter of time; 6% reduction of VE every 2 months, and the restoration to 95% VE by 3rd shot. It then recommends booster for all age 16+. Image Credit: Twitter

Any decision would depend on which vaccine is being evaluated and the data set being considered.