Breakthrough COVID-19 infections elicited greater humoral immune responses than the fourth dose of the BNT162b2 vaccine among patients with cancer. These findings were published in The Oncologist.

In January 2022, the Israeli Ministry of Health recommended that persons at high risk for infection receive a fourth dose of the BNT162b2 COVID-19 vaccine. However, there was little evidence to support this recommendation.

In this study, humoral immune responses in patients with cancer recruited at the Emek Medical Center in Israel were evaluated. Forty-one patients receiving ongoing anticancer treatment gave blood samples after receiving the third BNT162b2 vaccine dose and at 30 to 90 days following the fourth dose (11 patients) or a breakthrough infection (9 patients) or at 160 to 166 days after receiving the third dose (22 patients).

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The study population comprised 21 men and 21 women aged 63 to 68 years.

The patients received the fourth dose an average of 131 days after the third dose and breakthrough infections occurred 136.6 days after the third dose on average.

The control group who did not receive the fourth dose or have breakthrough infection had a decrease in anti-SARS-CoV-2 immunoglobulin (Ig)G titers from the first blood test to the second test (mean, 5379.95 vs 2314.00 AU/mL; P <.001), whereas a substantial increase in IgG titers was observed among patients with breakthrough infection (mean, 7050.50 vs 40,000.00 AU/mL; P <.001), even greater than fourth dose recipients (mean, 8389.00 vs 22,914.00 AU/mL; P =.033).

The increase in anti-SARS-CoV-2 IgG titers was significantly higher among the breakthrough infection group compared with the fourth vaccine dose recipients (P =.005).

The major limitation of this study was the small sample size.

These data indicated that among patients with cancer, protection from the third BNT162b2 vaccine waned compared with those who received a fourth dose. However, the greatest protection was observed following breakthrough infection.


Cohen I, Campisi-Pfinto S, Rozenberg O, Colodner R, Bar-Sela G. The humoral response of patients with cancer to breakthrough COVID-19 infection or the fourth BNT162b2 vaccine dose. Oncologist. Published online February 28, 2023. doi:10.1093/oncolo/oyad003