1. Patients receiving the fourth dose of BNT162b2 (Pfizer-BioNTech) showed reduced rates of symptomatic Covid-19 infection and hospitalization compared to their matched control over 30 days of follow-up.

2. Patients receiving the fourth dose of BNT162b2  were shown to have a lower rate of death compared to their matched control over 30 days of follow-up.

Evidence Rating Level: 2 (Good)

Study Rundown: Booster shots after the original, scheduled two-dose regimens of vaccines against Covid-19 are being considered to help combat the Covid-19 pandemic. Third doses of the BNT162b2 (Pfizer-BioNTech) vaccine have been administered worldwide; however, the vaccine effectiveness of a fourth dose is unknown. To assess the early effects of this fourth dose, patient data from a large health organization in Israel was extracted to compare Covid-19 related outcomes (symptomatic infection, hospitalization, or death) of patients receiving a fourth dose of the BNT162b2 vaccine compared to those only with three doses. Indeed, the study found that patients receiving the fourth dose had greater relative protection for the first 30 days against PCR-confirmed SARS-CoV-2 infection, symptomatic Covid-19 infection, hospitalization, and death. This study, therefore, provides preliminary evidence that a fourth dose of the BNT162b2 vaccines restores immune protection against Covid-19, at least within the first 30 days. The limitations of this study are notably related to the lack of analysis past the 30-day follow-up period to determine long-term effects and the possibility of confounding factors.

Click to read the study in NEJM 

Relevant Reading: Protection by a Fourth Dose of BNT162b2 against Omicron in Israel

In-Depth [case-control study]: Using patient data from a healthcare institution in Israel, extracted from a previous study, 182,122 patients receiving the fourth dose of BNT162b2 vaccine at least 4 months after their third dose, were control matched to another patient within the database who had only received three doses and had similar demographic and clinical variables. Over a follow-up period of 30 days, patients were assessed for incidence of any of the following Covid-19 related outcomes: PCR-confirmed infection, symptomatic infection, hospitalization, severe disease, or death. Risk ratios were calculated between groups for each outcome, and vaccine effectiveness was defined as 1 – the calculated risk ratio. Results were confirmed using sensitivity analyses. The study found that four doses of BNT162b2 protected patients against infection (vaccine effectiveness: 45%), symptomatic Covid-19 (55%), hospitalization (68%), severe disease (62%), and death (74%) within the first 30 days after vaccine administration compared to patients receiving only three doses. The rate of hospitalization in patients with four doses was 68.6 cases per 100,000 persons (95% Confidence Interval [CI], 48.5-91.9), which was significantly lower than those only with three doses at 180.1 cases per 100,000 persons (95% CI, 142.8-211.9). Taken altogether, this study demonstrates that the fourth dose of BNT162b2 offers early immune protection against Covid-19 related outcomes.

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