Do you need a second booster dose?

A health care worker receives a booster dose of Pfizer at Jackson Memorial Hospital on October 5 in Miami. Lynn Sladky/Associated Press, file

In late March 2022, the U.S. Food and Drug Administration authorized a second booster dose of COVID-19 vaccines to be given to at-risk populations in the United States, a move that the Centers for Disease Control and Prevention approved soon after. People 50 years of age or older and some immunocompromised people who are at increased risk of severe disease, hospitalization, and death are eligible four months after receiving the initial booster vaccine.

A second booster dose is equivalent to a fourth dose for people who received the Pfizer-BioNTech or Moderna mRNA series, or a third dose for those who received the Johnson & Johnson single vaccine.

In Israel, people in the same vulnerable groups began receiving fourth doses in January 2022. The UK recently started giving a fourth dose to people over 75 years of age and coined it as a “booster spring dose”. In Germany, people over 60 years of age are now eligible for a fourth snapshot of the mRNA sequencing.

I’m an epidemiologist at the University of Texas Health Science Center School of Public Health and founder and author of Your Local Epidemiologist, a newsletter that translates the latest public health science for everyday use.

Recent recommendations have left many wondering about the importance of boosters to protect against COVID-19. Is the third shot dwindling over time? Is the fourth dose necessary? What if I had a previous infection?

After reviewing the growing body of research on how the immune system shifts over time after each dose, it’s clear that another booster for the vulnerable has great benefit with very few risks.

Vaccine efficacy after the first booster dose

There is clear evidence that a third dose of the mRNA cascade – or the first booster dose – was and remains necessary to ensure a robust immune response against the omicron variant for all age groups. This is partly because the immune response diminishes over time and partly because omicron has been shown to be effective in part at evading immunity from current COVID-19 vaccines and from previous infections.

But then the question becomes: How strong is the immune system from the first booster over time?

The best real-time data for tracking vaccine efficacy over time is in the UK. The UK Health Security Agency currently has 15-week follow-up data after the third dose, or first booster dose. In its most recent report, the effectiveness of vaccines against infection diminishes significantly after a third dose. In the UK report, the efficacy of the vaccine against hospitalization holds up better than the efficacy against infection. But even protection from hospitalization diminishes slightly over time. While this data is insightful, 15 weeks of follow-up data is not very useful in the United States because many Americans get their third dose up to 24 weeks.

A recent study evaluated the durability of a third dose of Moderna after six months. The researchers found reduced levels of neutralizing antibodies after six months of taking the booster drug. The CDC also found a significant decrease in protection against emergency department and urgent care visits five months after the first booster dose. Vaccine efficacy against hospitalization decreased slightly but was largely discontinued after five months of booster.

The above studies collected all age groups. But researchers know that older adults do not have a lasting immune response like younger adults. This explains why superinfections occur at a much higher rate among people age 65 and older. A recent study in The Lancet evaluated the sustainability of a third dose among subjects aged 76 to 96 years. The researchers found that the third dose improved neutralizing antibodies, but against the omicron, the antibodies continued to decrease significantly after the boost.

Now that Israel has offered a fourth dose for several months, researchers have some data to rely on to assess its effectiveness. There are three studies released to date, one of which has not yet been peer-reviewed.

In one study published in the New England Journal of Medicine, scientists evaluated rates of infection and severe illness after a fourth dose — or a second booster dose — among more than a million people age 60 and older in Israel. The researchers found that after the fourth dose, the incidence of COVID-19 was twice as low as after the third dose. However, this protection soon waned after six weeks. They also found that the incidence of severe disease was four times lower compared to those who received only three doses. It is important to note, however, that hospitalizations between the two groups were very low.

Importantly, another study evaluated the efficacy of a fourth dose among younger health care workers in Israel. The results confirmed that antibody levels decreased significantly five months after the third dose. Unfortunately, the efficacy of a fourth dose was not different from that of a third dose in this group of younger healthcare workers. In other words, there may be no meaningful benefit from a second booster for the same formula for a healthy young population.

Researchers conducted a third study, not yet peer-reviewed, in a large healthcare system in Israel among people aged 60 to 100. Of the 563,465 patients in the healthcare system, 58% received a second booster dose. During the study period, 92 people who received a second booster dose died compared to 232 who received only the first dose. In other words, the second booster equates to a 78% reduction in mortality compared to the first booster alone.

What if I get COVID-19 infected with Omicron?

The combination of vaccination and infection with COVID-19 is called “hybrid immunity.” Over 35 studies have shown that hybrid immunity provides free and broad spectrum protection. This is because immunity from vaccines targets the thorny protein – and subsequently COVID-19 vaccines were designed – and immunity caused by infection targets the entire virus more broadly.

Therefore, it is not unreasonable to skip a second dose with a confirmed infection of the omicron. This does not mean that people should intentionally be infected with SARS-CoV-2, the virus that causes COVID-19. But it is clear that hybrid immunity is a viable route of protection.

In summary, there is strong evidence that a fourth dose – or a second booster dose – provides meaningful protection among vulnerable populations, including people over 60 years of age. So the other reinforcer is reasonable for some groups. And while the fourth dose may benefit a specific group, it is very important that people receive their first, second, and third doses.


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