4th dose of mRNA Covid-19 vaccine significantly increases protection at age 60+
4th dose of mRNA Covid-19 vaccine significantly increases protection at age 60+

4th dose of mRNA Covid-19 vaccine significantly increases protection at age 60+

In a recent study published in New England Journal of Medicinecompares researchers the effectiveness of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Pfizer-BioNTech BNT162b2 third- and fourth-dose vaccinations in Israel.

Examination: Fourth dose of BNT162b2 mRNA Covid-19 vaccine in a nationwide environment. Image credit: WESTOCK PRODUCTIONS / Shutterstock.com


On January 3, 2022, the Israeli Ministry of Health launched national fourth-dose SARS-CoV-2 vaccination services for at-risk populations, including individuals over 60 years of age and immunocompromised individuals, approximately four months after receiving their third vaccine dose. Other nations that have launched campaigns for the fourth dose of coronavirus disease vaccine 2019 (COVID-19) included the United States and the United Kingdom.

SARS-CoV-2 fourth dose vaccine rollout was initiated in response to persistent waves of COVID-19 cases caused by the SARS-CoV-2 Omicron (B.1.1.529) variant, combined with decreasing protection after the third boosting dose of COVID- 19 vaccines. The effects of the Omicron-driven wave were even observed in nations with successful COVID-19 mass vaccination initiatives.

A recent report provided real-time evidence of the efficacy of a fourth dose of the SARS-CoV-2 BNT162b2 vaccine, indicating that this additional booster is more effective in preventing COVID-19 and severe SARS-CoV-2 infection than three doses. alone . Nevertheless, the trial did not provide information on the efficacy of a fourth dose to prevent further COVID-19 outcomes, such as hospitalization and mortality. In addition, several potentially relevant confounders, such as the presence of comorbidities, were not treated.

About the study

In this study, the researchers evaluated the early efficacy of a fourth dose of the SARS-CoV-2 BNT162b2 vaccine to prevent a range of COVID-19-associated outcomes in high-risk populations by analyzing data obtained from the largest Israeli health facility between January 3 and 18 February 2022 while checking for possible confounders.

The authors evaluated five SARS-CoV-2-related outcomes, including: polymerase chain reaction (PCR) -confirmed COVID-19, symptomatic SARS-CoV-2 infection, COVID-19-associated hospitalization, severe SARS-CoV-2 infection, and COVID -19-associated death.

Additionally, the disruptive factors controlled in this research were age, gender, place of residence, population, calendar month of receiving the third dose, the number of chronic existing comorbidities characterized as severe COVID-19 risk factors by the US Centers for Disease Control and Prevention (CDC ) and number of admissions in the last three years.

The researchers examined the relative efficacy of a fourth dose of the COVID-19 vaccine compared to a third dose administered almost four months earlier in individuals 60 years of age or older at the personal level. In addition, both cohorts were matched by different clinical and sociodemographic variables. A total of 182,122 matched pairs were included in the primary analysis.

Survey results

The comparative vaccine efficacy for one week to one month after the fourth dose of BNT162b2 vaccine was estimated to be 45% against PCR-confirmed COVID-19, 55% against symptomatic SARS-CoV-2 infection, 68% against COVID-19-linked hospitalization, 62% against severe SARS-CoV-2 infection and 74% against COVID-19-associated mortality. The corresponding estimates for two weeks to one month post-fourth dose were 52%, 61%, 72%, 64%, and 76%, respectively.

For one week to one month after the fourth dose, the variation in absolute risk between three and four doses was 180.1 cases / 100,000 people for COVID-19 associated hospitalization and 68.8 cases / 100,000 people for severe SARS-CoV-2 -infection. Furthermore, estimates of relative vaccine efficacy against reported SARS-CoV-2 infection in susceptibility analyzes were comparable to the values ​​in the primary evaluations.

Individuals in the fourth dose group have a low risk of confirmed COVID-19 in the first few days of follow-up shortly after their vaccination. Additionally, vaccinated individuals underwent SARS-CoV-2 testing less frequently in the first few days after immunization, which was likely because they associated any symptoms with the adverse effects of the vaccine. Nevertheless, this bias was a temporary event, evidenced by almost equal risks in the vaccine groups with three and four doses on days five and six.

After this, the fourth dose of the vaccine started to work around week 1, with the effect gradually increasing to a stable level around week 2. Given the remarkably modest variation between the two groups on days five and six, the majority of the subsequent difference is attributed to the efficacy of a fourth vaccine dose.


The results of the current real-world study showed that a fourth dose of the COVID-19 BNT162b2 vaccine was effective against the SARS-CoV-2 Omicron variant, at least in the beginning. The study showed that the fourth dose of BNT162b2 vaccine increases protection against PCR-confirmed COVID-19, symptomatic SARS-CoV-2 infection, COVID-19 associated hospitalization, severe SARS-CoV-2 infection and COVID-19-associated mortality compared to a third booster dose given at least four months before among persons over 60 years of age.

Extended follow-up will provide a more in-depth evaluation of the fourth dose of long-term protection. Although these data help alleviate some concerns, the authors say more research is needed to determine whether vaccination is less frequent or the delivery of a mixture of several SARS-CoV-2 vaccines is a better long-term policy to curb it. ongoing COVID-19 pandemic.

Taken together, current work demonstrated that a fourth BNT162b2 COVID-19 vaccine dose was beneficial in minimizing the short-term risk of SARS-CoV-2-associated outcome in at-risk individuals who had previously received a third vaccine dose.

Journal reference:

  • Magen, O., Waxman, JG, Makov-Assif, M., et al. (2022). Fourth dose of BNT162b2 mRNA Covid-19 vaccine in a nationwide environment. New England Journal of Medicine. doi: 10.1056 / NEJMoa2201688.

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