Covid-19: Booster mRNA Vax Dosing Shows Clear Benefits in Israeli Cohort

Recent recipients of a third dose of the BNT162b2 Covid-19 vaccine were less likely to be hospitalized or die from the disease compared to fully vaccinated people who did not receive a booster dose in a study from Israel involving more than 1.4 million people.

The analysis of data from Israel’s largest health service provider compared outcomes among people receiving a third vaccine dose to demographically and clinically matched non-booster controls who received a second dose of BNT162b2 at least five months before recruitment.

Though hospitalizations and deaths related to Covid-19 were low in both groups, the findings, published online Oct. 29 in The Lancet, showed that booster dosing offered clear benefits for both these outcomes.

“To our knowledge, the present study is the first to estimate the effectiveness of a third dose of an mRNA Covid-19 vaccine—BNT162b2 specifically—against severe outcomes with adjustment for various possible confounders, including comorbidities and behavioral factors, and within subgroups,” wrote researcher Noam Borda, of Clalit Research Institute, Tel Aviv, Israel, and colleagues.

They noted that compared with two doses of the vaccine administered at least 5 months before, adding a third dose was estimated to be between 81% and 93% effective in preventing severe disease, hospitalization, and death due to Covid-19.

The study involved data from Clalit Health Services, which covers over half of the Israeli population. Health plan enrollees receiving a third vaccine dose between July 30, 2020, and Sept. 23, 2021, were matched to demographically and clinically similar controls who did not receive a third dose, but who were fully vaccinated (two doses) at least five months prior to recruitment.

None of those included in the study had previous documented SARS-CoV-2 infection, and none had contact with the health-care system in the three days before recruitment. Health-care workers, residents of long-term care facilities, and individuals who were medically confined to their homes were not included in the study.

The two matched groups each included 728,321 people, the median age of the study participants was 52 years (IQR 37–68), and 51% were female. Median follow-up was 13 days (IQR 6–21) in both groups.

Vaccine effectiveness evaluated at least seven days after receipt of the third dose, compared with receiving only two doses at least five months prior, was estimated to be:

• 93% for hospital admission (231 events for two doses versus 29 events for three doses; 95% CI, 88-97).
• 92% for severe disease (157 versus 17 events; 95% CI, 82-97).
• 81% for Covid-19 related death (44 versus 7 events; 95% CI, 59-97).

Booster dose efficacy against hospitalization and severe disease was found to be similar in males and females, and in age groups 40-69 years and 70 year and older. The researchers noted that, in individuals age 16-39 years, “the rate of these severe outcomes was too small for meaningful estimation of the booster effectiveness.”

Study limitations included the lack of data on less severe Covid-19 secondary outcomes, including documented infection and symptomatic infection, and the possibility of confounding inherent in all observational studies. The findings also did little to clarify the need for boosters in younger (<40 years) adults, due to the small number of events in this age group.

In an accompanying commentary, K. Srinath Reddy, MD, president of the Public Health Foundation of India, wrote that while the study was well designed and used clinically relevant endpoints, the generalizability of the findings to the mRNA-1273 vaccine remains unknown, given that several previous reports suggest a steeper decline in immunity in the months following full vaccination with the BNT162b2 vaccine than with mRNA-1273.

A recently published study from the Kaiser Permanente health group showed a 53% drop in BNT162b2 vaccine effectiveness against infection with the SARS-CoV-2 Delta variant 4 months after full vaccination, although protection against hospitalization remained high.

“Although these reports strengthen the case for a booster dose of BNT162b2, there is no evidence yet to suggest that global policies related to other vaccines should be influenced by this experience,” Reddy wrote, adding that the risk versus benefits of booster dosing for younger adults and adolescents remains unclear.

Reddy wrote that the issue of vaccine inequality across nations remains “a matter of global concern,” noting that if “the practice of administering a third dose to all individuals older than 12 years becomes established in vaccine-rich countries, it can aggravate supply shortages for other countries.”

“In this scenario, under-vaccinated populations could generate the conditions for the emergence of new variants, which might not only be more infectious but also exhibit greater immune escape, and those variants might enter vaccine-rich countries to trigger fresh waves of infection,” Reddy wrote.

“That is not the kind of natural experiment the world would like to see. As countries discharge their responsibility to protect vulnerable individuals in their populations, they must ensure adequate supply to other countries. Global policy must weigh the risks of adopting booster doses ad libitum across the world at this stage in the pandemic.”

1. Recent recipients of a third dose of the BNT162b2 Covid-19 vaccine were less likely to be hospitalized or die from the disease compared to fully vaccinated people who did not receive a booster dose.

2. Compared with two doses of the vaccine administered at least five months before, adding a third dose was estimated to be between 81% and 93% effective in preventing severe disease, hospitalization, and death due to Covid-19.

Salynn Boyles, Contributing Writer, BreakingMED™

Cat ID: 190

Topic ID: 79,190,730,933,190,31,926,561,927,925,934