Lower COVID-19 Infection Rate With Fourth Dose of BNT162b2 Vaccine in Autoimmune Rheumatic Diseases

Compared with 3 doses of the COVID-19 vaccine, the fourth dose was associated with favorable outcomes in patients with autoimmune rheumatic diseases.

The fourth dose of the BNT162b2 vaccine is associated with a lower COVID-19 infection rate among patients with autoimmune rheumatic diseases (ARDs), according to study results published in Rheumatology.

Compared with the general population, patients with ARDs have a higher risk for hospitalization and death resulting from COVID-19 infection.

The aim of the study was to determine the benefits of the fourth dose of the Pfizer-BioNTech (BNT) 162b2 COVID-19 vaccine in individuals with ARDs.

The retrospective analysis included adult patients with ARDs who were enrolled in Israel’s largest health management organization. Participants who did not have a prior COVID-19 diagnosis were eligible for inclusion in the study.

Data were collected from electronic health records between January and March 2022.

Participants were assigned to a control group (those receiving 3 doses of the BNT162b2 vaccine) or a treatment group (those who received a fourth dose as well).

We found that the fourth dose may have an added benefit among this vulnerable population by reducing COVID-19 infections, hospitalizations, and deaths.

The primary study outcome was COVID-19 infection, and secondary outcome measures were COVID-19-related hospitalizations and death.

A total of 27,766 and 15,982 individuals were included in the control and treatment groups, respectively.

Researchers observed that 6942 (25.0%) of the control group and 1754 (11.0%) of the treatment group experienced COVID-19 infection (P <.001). In the entire cohort and each subgroup, individuals who received a fourth dose had a lower risk for infection (hazard ratio [HR], 0.54; 95% CI, 0.52-0.58), regardless of baseline medical treatment, except for rituximab. The risk was also lower for COVID-19-related hospitalization (HR, 0.36; 95% CI, 0.22-0.61) and death (HR, 0.41; 95% CI, 0.24-071).

Study limitations included the inability to determine causality between the fourth dose and COVID-19 outcomes because of the retrospective design; the inclusion of patients with ARDs without a prior COVID-19 diagnosis may have compromised the validity of the results; and the baseline measures did not include external factors such as adherence to treatments or risk aversion.

The study authors concluded, “We found that the fourth dose may have an added benefit among this vulnerable population by reducing COVID-19 infections, hospitalizations, and deaths.”

They also suggested that providers should encourage patients with ARDs to stay up-to-date on their COVID-19 booster doses by reassuring them of the effectiveness of the vaccine.


Bieber A, Brikman S, Novack L, et al. Fourth dose of BNT162b2 vaccine for patients with autoimmune rheumatic diseases in a nationwide setting. Rheumatology. Published online February 10, 2023. doi:10.1093/rheumatology/kead064