ECDC & WHO have released statements indicating that while a 4th dose may be beneficial to populations at highest risk of severe outcomes, marginal benefits for other populations may be outweighed by the opportunity and financial cost
Extensive analysis of data from Israel’s 4th dose campaign indicates that while protection against severe disease and death remains high following 3rd dose, the administration of a 4th dose significantly increases protection against infection and symptomatic disease, though this protection appears short-lived, with protective effects waning by 10 weeks
Israeli healthcare workers demonstrate an increase in immunity markers following 4th dose, but protection against infection remains low
In immunocompromised individuals (such as solid organ transplant patients and dialysis patients), receipt of a 4th dose of COVID-19 vaccine increases immunity marker titers, but non-responders continue to have a low likelihood of de novo seroconversion
Key Findings
March 31, 2022
Data from Israel of adults 60 years and older who received a 4th dose of mRNA vaccine found that the rate of confirmed infection decreased ~2 fold following the 4th dose, and the rate of severe illness decreased by ~4-fold in those who received a 4th dose versus those with 3 doses, both results were found to be statistically significant
NACI recommends a 4th dose at least 6 months following a 3rd dose for severely immunocompromised individuals who are not only at higher risk of severe outcomes, but also at higher risk of decreased protection over time following vaccination – this recommendation has been echoed by Public Health Ontario, the Northwest Territories Health and Social Services
The FDA has also authorized the use of the Pfizer mRNA vaccine as a 4th dose for adults over 50 years and those over 12 years with compromised immune systems
A small study of Israeli healthcare workers compared the incidence of COVID-19 in those who had received a 4th dose of vaccine to those who had received only three doses. It found that protection from Omicron infection was only slightly higher in the four-dose vaccine group compared to the three-dose control group (31% for Pfizer as a 4th dose, 11% for Moderna as a 4th dose), and that neither result was statistically significant. Breakthrough infections were mild, yet with high viral loads
Small-scale studies of solid-organ transplant and hemodialysis patients found that while a 4th dose increased antibody titers in most participants, those with severe immune deficiencies such as those taking anti-rejection medication were still unable to mount an immune response to vaccination – in addition, these studies have not assessed the presence or strength of functional immunity in these populations
Badea, A; Dalidowicz, M; Howell-Spooner, B; Groot, G; Reeder. B. What is the efficacy of a 4th booster dose for COVID-19? 2022 Jun 07. Document no.: EOC220304v002 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2022. 12 p. (CEST rapid review report).