A second booster shot of the Pfizer-BioNTech vaccine provides additional short-term protection against Omicron infections and severe illness among older adults, according to a large study from Israel. However, the boosterʼs effectiveness against infection in particular wanes after just four weeks and almost disappears after eight weeks.
Protection against severe illness did not ebb in the six weeks after the extra dose, but the follow-up period was too short to determine whether a second booster provided better long-term protection against severe disease than a single booster.
The New York Times reports that the study focused on adults aged 60 and older, and did not provide data on the effectiveness of a second booster in younger populations.
The findings, published in The New England Journal of Medicine, suggest that additional boosters are likely to provide fleeting protection against Omicron infections in older recipients, and are consistent with evidence that vaccine effectiveness against infection wanes faster than against severe disease.
“For confirmed infection, a fourth dose appeared to provide only short-term protection and a modest absolute benefit,” the researchers wrote.
The results come amid a debate over whether and when Americans might need additional boosters. The US Food and Drug Administration (FDA) is convening a panel of outside advisers this week to discuss the broader US booster strategy.
The rapid spread of the highly transmissible Omicron variant, which can evade some of the bodyʼs immune defences, has intensified the discussion of whether second boosters are broadly necessary.
Last month, the FDA authorised second booster shots of the Pfizer-BioNTech and Moderna vaccines for adults 50 and older, as well as immunocompromised people aged 12 and older. The agency also authorised an mRNA booster for adults who have already received two doses of the Johnson & Johnson vaccine.
While 66% of Americans have been vaccinated, just 30% have received a booster shot.
It is clear Omicron as blunted the effectiveness of COVID vaccines, but data on the benefits of a second booster remain limited. A previous study from Israel, which has not yet been published in a scientific journal, found that older adults who received a second booster were 78% less likely to die of COVID-19 than those who had received just one booster shot.
But scientists criticised the studyʼs methodology, and the benefits of a second booster for young, healthy adults are less clear. Some experts note that most adults who have been vaccinated and boosted once are already likely to be protected from severe illness and death.
On 2 January, Israel authorised a fourth dose of the Pfizer-BioNTech vaccine for adults 60 and older and other high-risk populations who had received their third shots at least four months earlier. Israelʼs vaccination campaign has relied heavily on the Pfizer-BioNTech vaccine.
The new study is based on records from the Israeli Ministry of Health of more than 1.2m older adults who were eligible for the fourth shot between 10 January and 2 March, when Omicron was the dominant variant in the country.
The researchers compared the rate of confirmed virus infections and cases of severe COVID-19 among those who had received a fourth dose with those who had received just three doses.
Protection against infection appeared to peak four weeks after the fourth shot: the rate of confirmed infections was twice as high in the three-dose group as in the four-dose group. By eight weeks after the fourth shot, however, the additional protection against infection had almost disappeared, the researchers found.
Rates of severe disease were 3.5 times higher in the three-dose group than the four-dose group four weeks after the booster shot, the researchers found. That protection did not appear to wane and actually ticked up slightly by the sixth week after the shot, when rates of severe disease were 4.3 times higher in the three-dose group.
But the study covered a relatively short period, and whether the benefits against illness hold up over the longer term remains unknown. The study did not report data on deaths.
Dr Rochelle Walensky, director of the US Centers for Disease Control and Prevention (CDC) said her agency “encourages people over 50 who have underlying medical conditions and those over 65” to get a second booster shot.
Last week, the FDA authorised a second booster of Pfizer-BioNTech or Modernaʼs vaccines for everyone over 50 and many immunocompromised people, four months after the first booster. Walensky said that the option was “especially important” for those over 65, as well as for those over 50 with chronic health problems, such as diabetes or obesity.
The decision to offer a second booster continues to generate controversy, with some immunologists and vaccine experts arguing that the federal government lacked enough data to justify the move, at least for those under 65.
At least 30m Americans are now eligible for a second booster dose, including 10m people between 50 and 64 years, and 20m people 65 and older, a CDC spokesman said.
Federal regulators initially leaned toward giving everyone 60 or 65 and older the option of a second booster, based heavily on data from Israel, which has been offering the additional shot to those 60 and older since early January. They decided to include people as young as 50 because about one-third of Americans between 50 and 65 have serious health problems.
Protection by a Fourth Dose of BNT162b2 against Omicron in Israel
Yinon M. Bar-On, Yair Goldberg, Micha Mandel, Omri Bodenheimer, Ofra Amir, Laurence Freedman, Sharon Alroy-Preis, Nachman Ash, Amit Huppert, and Ron Milo.
Published in The New England Journal of Medicine on 5 April 2022
On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (COVID-19).
Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe COVID-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.
The number of cases of severe COVID-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe COVID-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks.
Rates of confirmed SARS-CoV-2 infection and severe COVID-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.
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