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What do we know about second COVID-19 booster shots?


by Health Desk

Published on April 1, 2022

What our experts say

Several countries have recently rolled out programs to offer a second COVID-19 booster shot to their most vulnerable populations: older people and those with compromised immune systems. Israel, Denmark, Hungary, Chile, Sweden, and the United States are among the countries who have approved an additional booster shot for the elderly and those with underlying conditions. In most of these countries, the second booster shot will be the fourth shot following an initial two-shot mRNA vaccine.

Though most nations offering a second booster are using Pfizer-BioNTech and Moderna mRNA vaccines, Sinovac and AstraZeneca's shots are also being used in some countries.

However, many scientists are conflicted about this guidance as recent findings about the effectiveness of a second booster shot are mixed.

A fourth shot of an mRNA vaccine was found to boost antibody levels in Israeli healthcare workers who received a jab, but was not particularly good at preventing infection against the Omicron variant. Authors of this study also noted that a fourth vaccine would provide "little protection" over three doses for healthy, younger, populations.

Another (preprint) study from Israel in January 2022 showed that a second booster shot led to a five-fold increase in antibody levels. These preliminary findings also suggest that a fourth mRNA dose is safe and would be effective at increasing protection against infection, hospitalization, and death.

The World Health Organization has implied that such wide-ranging booster programs will increase vaccine inequity and cause the pandemic to continue even further as vaccines are going to countries with strong vaccine coverage and not those with limited access. While the virus continues to impact people in countries without large vaccine coverage, it will likely keep mutating and spreading further because there are more unprotected people to infect. These viral changes might make the virus less susceptible to the vaccine's effectiveness in the future.

The European Medicines Agency (EMA) has said more information is needed to understand the impact of the Omicron variant on currently approved COVID-19 vaccines and first boosters. Individual experts from the EMA have also expressed that based on current evidence, repeat vaccinations in short periods of time are not a sustainable long-term strategy.

Other immunology experts have shared that frequent booster shots could potentially cause T-cell "exhaustion,” meaning that repeated exposure to an antigen or pathogen like those in the COVID-19 vaccines could cause dysfunction in T-cells, which are important for our immunity.

However, there is still a lot we don’t know about if or how this might happen in the case of COVID-19 vaccination. This is because most of the current research on T-cell exhaustion comes from science on conditions like HIV or cancer, when the antigen is present all the time. There is no current evidence of T-cell exhaustion as a result of COVID-19 vaccines. As a result, health experts have said that T-cell exhaustion should not guide policy at this time, but is a concern that we should monitor for.

Countries are currently trying to develop such policies on a second booster by weighing any potential, unknown risks with known benefits. In the Philippines, for instance, health officials have decided that protecting those most susceptible to a dangerous infection is a priority, and Rollout of a second booster shot for vulnerable people may start as early as the end of April.

More research and time is needed to know how often we might need COVID-19 booster shots over time, how effective they are, and what groups need to be prioritized.

Context and background

Second booster shots are being considered as variants of COVID-19 continue to spread and impact the global population, and as immunity of initial vaccines and boosters have been shown to decrease after about four months.

Second booster shots are for now being considered and approved only for the most populations most vulnerable to COVID-19: the elderly and the immunocompromised.

There are several reasons why the fourth shot policies focus on these two groups. The first is that the immune system ages over time and does not produce the same amount of antibodies as it used to, nor does it tend to react as effectively against pathogens as it used to. Another reason is that older adults tend to develop medical conditions that require the body's attention, like hypertension, obesity, and diabetes. These types of conditions are also risk factors for severe disease from COVID-19. Immunocompromised people are in need of greater protection against COVID-19 as they are more susceptible to being infected with the virus.


  1. Science unclear around fourth COVID-19 shot (Harvard T.H. Chan School of Public Health)
  2. Sweden recommends fourth vaccine shots for people 80 and older. (New York Times)
  3. CDC Recommends Additional Boosters for Certain Individuals (Centers for Disease Control and Prevention)
  4. Covid: Chile starts fourth vaccine dose amid rise in cases (BBC News)
  5. Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron (The New England Journal of Medicine)
  6. Fourth COVID-19 vaccine dose boosts antibodies five-fold in Israeli study, PM says (Reuters)
  7. Fourth COVID Shot Boosts Protection Fivefold, Israeli Study Suggests (Haaretz)
  8. COVID: Do multiple boosters 'exhaust' our immune response? (DW)
  9. Jury still out on omicron and vaccines, says EU drugs regulator (DW)
  10. Rollout of 4th COVID-19 vaccine dose for vulnerable population may start at last week of April (Inquirer)
  11. Scientists said we’d take annual COVID jabs like flu shots. Now Fauci says it might be only every 5 years (Fortune)
  12. covid-19 vaccine stock photo ig: @hakannural

Used with Permission from Health Desk, a public health hub that explains emerging COVID-19 science.

This article was written and edited by the Tayo editorial desk and has been reviewed by an independent panel of subject matter experts.

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