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A new, large-scale study investigates the effectiveness of COVID-19 vaccine boosters. Martin Rickett – PA Images/Getty Images
  • A team of researchers from Israel and the United States recently analyzed the effectiveness of a third dose of the Pfizer COVID-19 vaccine for preventing severe COVID-19 outcomes.
  • They found that an additional, “booster,” shot may reduce the risk of severe complications, compared with only two vaccine doses.
  • However, global inequities and vaccine hesitancy are persisting challenges to the vaccination effort.

SARS-CoV-2 infections have been resurgent in many areas of the world throughout 2021, driven primarily by the Delta variant.

Healthcare officials worry that the effectiveness of current vaccination is waning, not holding up against this new strain. In response, many governments want to administer booster doses of COVID-19 vaccines.

The Israeli government deployed third doses of the Pfizer vaccine before and during the country’s fourth wave of the pandemic in the summer of 2021.

A team led by scientists from Harvard University and Israel’s Clalit Research Institute recently concluded that this extra inoculation could significantly reduce the risk of severe complications of COVID-19.

Their paper, which appears in The Lancet, summarizes the largest peer-reviewed study of a COVID-19 booster dose to date. This investigation is also the first to gauge how well a third dose of the Pfizer vaccine works to prevent severe outcomes.

The team analyzed data from Clalit Health Services, Israel’s largest healthcare organization.

The scientists followed 728,321 individuals who received a third Pfizer COVID-19 vaccine between July 2020 and September 2021. These participants were matched with an equal number of people who only received two doses of the vaccine.

The authors explain: “In this study, we estimated effectiveness starting from day 7 after the third dose, which is similar to the period used to define full vaccination after the second dose. Our choice is supported by high concentrations of antibodies in individuals 7 days after administration of the third dose.”

Primary outcomes included hospital admission related to COVID-19, severe disease, and mortality, according to National Institutes of Health (NIH) criteria.

As part of their analysis, the researchers adjusted for possible confounding factors, including sociodemographic factors, existing health conditions, and behavioral factors.

The data showed that people who received the COVID-19 booster shot had a 93% lower risk of hospital admissions, compared with people who had their second shot at least 5 months prior.

Similarly, people with a third dose had a 92% lower risk of severe disease and an 81% lower risk of death from COVID-19.

According to the team, the estimated effectiveness of the third dose against hospital stays and severe complications “was similar between males and females, and between individuals aged 40–69 years and those aged at least 70 years.”

The Food and Drug Administration (FDA) expanded the use of COVID-19 vaccine boosters under certain circumstances. Currently, the Centers for Disease Control and Prevention (CDC) recommend booster doses for people who are:

  • 65 years or older
  • 18 years or older and have an underlying medical condition
  • 18 years or older and living or working in high-risk settings
  • 18 years or older and received a Johnson & Johnson COVID-19 vaccine

The CDC also says that people can choose which COVID-19 booster vaccine to receive.

In a Kaiser Family Foundation survey, 43% of fully vaccinated adults said that they “will definitely” get a COVID-19 booster vaccine when it becomes available. Another 24% said that they “probably will” if it is recommended for people like them. By the time the survey was completed in October 2021, 10% of respondents had already received a booster.

More than 15 million people in the U.S. had already received a COVID-19 vaccine booster as of October 28, 2021.

Eligible but unaware

Donald J. Alcendor, Ph.D., is an assistant professor of cancer biology at Meharry Medical College. He is also an adjunct associate professor of pathology, microbiology, and immunology at Vanderbilt University School of Medicine.

In an interview with Medical News Today, Dr. Alcendor noted that many people in the U.S. are eligible for boosters but do not realize it.

He explained that the CDC’s guidelines for eligibility apply to people who are at least 18 years old and have an underlying medical condition, such as:

  • asthma
  • diabetes
  • heart conditions
  • chronic lung diseases
  • overweight or obesity
  • a substance use disorder

Special cases

Dr. Katherine O’Brien is a professor at the Bloomberg School of Public Health and serves as the executive director of the International Vaccine Access Center, at Johns Hopkins University.

On a World Health Organization (WHO) podcast in September 2021, she explained why some people might need a booster:

“The first is […] if you’re in a category of people that didn’t respond adequately to the first two doses that you received. We do have some information that for some immunocompromised people, it may be necessary to receive a third dose because those first two aren’t doing what they do in otherwise normal, healthy people.”

Dr. O’Brien also said that vaccine protection may deteriorate over time. However, she noted: “We don’t see strong evidence leading to a need to provide a third dose for people who have already been vaccinated.”

Dr. Alcendor is concerned that millions of people in the U.S. remain unvaccinated against COVID-19. He has also observed intensifying qualms among vaccine-hesitant individuals and parents who are protesting vaccine mandates for children.

“This will result in unvaccinated populations across the U.S. that will allow this virus to continue to evolve and induce breakthrough infections in the general population to expand this pandemic.”

Further, he warns that, “Global inequities in vaccine distribution represent a silent storm that will have to be dealt with in the same manner as we did for polio and smallpox.”

In the WHO podcast, Dr. O’Brien elaborated on this point:

“We’re in a really inequitable place right now about who has already received the first and the second doses to provide protection against the severe outcomes. In low-income countries and low [to] middle-income countries, they are only at about 1%, 2%, 5% of the population having received [the] vaccine already.”

“So, the focus now for the supply needs to be to protect those people who are not yet protected at all by vaccines. It will reduce transmission, it will reduce the likelihood of more variants emerging, and it will give us time to see more of the evidence about whether or not booster doses will eventually be needed.”

– Dr. Katherine O’Brien

This study’s authors mention several limitations. First, they could not generate reliable estimates about secondary outcomes; namely, infection and symptomatic infection.

Also, as an observational study, this analysis could not account for every factor that may have influenced the outcomes.

In addition, the authors mention that “Due to the relative scarcity of events in individuals younger than 40 years, we could not evaluate vaccine effectiveness in this age group.”

The scientists also acknowledge that “This vaccine effectiveness study did not explore potential adverse clinical events and excess healthcare utilization associated with the administration of a third dose.”

The study excluded people who were likely to have had their booster doses early; this included healthcare workers and long-term care facility residents.

Meanwhile, several of the authors were affiliated with or compensated by Pfizer. MNT asked Dr. Alcendor, who was not involved in the research, if these links to the company may have influenced the study’s outcomes.

He answered: “Vaccine manufacturers are always in the process of doing damage control for their bottom line, but that’s why we have a data safety monitoring board, the FDA advisory committee […] and the CDC advisory committee, who are impartial and there to watch over us. There is always a chance for the mishandling of data, but the oversight for vaccines is quite rigorous.”

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