At the end of March 2022, the American Food and Drug Administration authorized a second recall COVID-19 vaccines for vulnerable populations in the United States, a decision that was shortly after approved by the Centers for Disease Control and Prevention. People aged 50 and over and some immunocompromised people who are at higher risk of serious illness, hospitalization and death are eligible four months after receiving the initial booster dose.
In Israel, people belonging to these same vulnerable categories started receiving fourth doses in January 2022. The UK has recently started administering a fourth dose to people 75 and over and invented it a “spring return.” In Germany, those over 60 are now eligible for a fourth shot in the mRNA series.
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The latest recommendations have left many wondering about the importance of reminders for protection against COVID-19. Does the third hit decrease over time? Is a fourth dose necessary? What to do if you have already had an infection?
After reviewing the growing body of research on how the immune system changes over time after each dose, it’s clear that another booster for vulnerable populations has significant benefits with very little risk.
Vaccine efficacy after the first booster dose
There is clear evidence that a third dose of the mRNA series – or the first booster dose – was and still is essential to ensure a robust immune response against the omicron variant for all age groups. This is partly because the immune response decreases over time and also partly because omicron has been shown to be partially effective in evading immunity from existing COVID-19 vaccines and past infections.
But then the question becomes: how long does first-recall immunity last?
The best real-time data to track on vaccine effectiveness over time is in the UK. The UK Health Safety Agency currently has follow-up data for 15 weeks after the third dose or first booster. In his last report, the effectiveness of vaccines against infection drops significantly after a third dose. In the UK report, vaccine efficacy against hospitalization fared much better compared to efficacy against infection. But even the protection against hospitalization decreases slightly over time. While this data is insightful, 15 weeks of follow-up data isn’t very helpful in the United States because many Americans received their third dose up to 24 weeks ago.
A recent study assessed the durability of a third dose of Moderna after six months. The researchers found a decrease in levels of neutralizing antibodies six months after the booster. The CDC also found significant decreasing protection against visits to the emergency room and urgent care five months after the first reminder. Vaccine efficacy against hospitalization declined somewhat but was largely maintained five months after the booster.
The studies mentioned above pooled all age groups. But researchers know that older people don’t develop as long-lasting an immune response as younger people. This explains why breakthrough infections have occurred at a higher rate in people aged 65 and over. A recent Lancet study assessed the durability of a third dose in people aged 76 to 96. The researchers found that the third dose improved neutralizing antibodies, but against omicron, antibodies still declined significantly after a booster.
Second Booster/Fourth Injection Data
Now that Israel has been delivering a fourth dose for several months, researchers have some data to draw on to assess its effectiveness. Three studies have been published to date, including one that has not yet been peer-reviewed.
In a study published in the New England Journal of Medicine, scientists evaluated the rate of infection and severe illness after a fourth dose – or second recall – among more than one million people aged 60 and over in Israel. The researchers found that after a fourth dose, the COVID-19 infection rate was twice as low as after a third dose. However, this protection quickly waned after six weeks. They also found that the rate of severe illness was four times lower than in those who received only three doses. It is important to note, however, that hospitalizations among both groups were very low.
Above all, another study evaluated the effectiveness of a fourth dose in young health care workers in Israel. The results confirmed that antibody levels dropped significantly five months after the third dose. Unfortunately, the efficacy of the fourth dose was no different from the efficacy of a third dose in this population of young healthcare workers. In other words, there may not be a significant benefit from a second booster of the same formula for young, healthy populations.
The researchers conducted a third study, one that has not yet been peer-reviewed, in a large health care system in Israel among people aged 60 to 100. Of 563,465 patients in the healthcare system, 58% received a second booster. During the study period, 92 people who received the second booster died compared to 232 people who received only the first booster. In other words, the second booster equates to a 78% reduction in deaths compared to the first booster alone.
What if you had a COVID-19 infection with omicron?
The combination of being both vaccinated and having been infected with COVID-19 is called “hybrid immunity.” More … than 35 studies showed that hybrid immunity provides complementary and broad protection. This is because vaccine immunity targets the spike protein – after which the COVID-19 vaccines were designed – and the immunity induced by the infection more broadly targets the entire virus.[Over 150,000 readers rely on The Conversation’s newsletters to understand the world. Sign up today.]
It is therefore not unreasonable to skip a second booster with a confirmed omicron infection. That doesn’t mean people should deliberately catch SARS-CoV-2, the virus that causes COVID-19. But it’s clear that hybrid immunity is a viable route to protection.
In short, there is strong evidence that a fourth dose – or second booster – offers significant protection among vulnerable populations, including people over 60. So another reminder is reasonable for some groups. And while a fourth dose may benefit a select group, it is far more important that people get their first, second and third doses.
Katelyn Jetelinaassistant professor of epidemiology, University of Texas Health Sciences Center at Houston