The Humoral Response of Patients With Cancer to Breakthrough COVID-19 Infection or the Fourth BNT162b2 Vaccine Dose

Abstract

Since January 2022 in Israel, high-risk populations with underlying health conditions were advised to receive a fourth dose of the BNT162b2 vaccine (Pfizer-BioNTech) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We monitored vaccine-induced immunity among oncology patients undergoing systemic anti-cancer therapy before and after the 4th-BNT162b2-dose. Three groups of patients were included in the study: those who received 3rd-BNT162b2-dose and had no breakthrough infection (control), those who received 3rd-BNT162b2-dose and had the breakthrough infection, and those who received the 4th-BNT162b2-dose and had no breakthrough infection. Anti-SARS-CoV-2 immunoglobulin-G (IgG) levels of the control group exhibited a rapid decrease over time, whereas IgG titers of patients with breakthrough-infections or patients vaccinated with the 4th-BNT162b2-dose were considerably elevated, consistent with the capacity of the second booster to induce anti-SARS-CoV-2 IgG levels. Additionally, oncology patients' humoral immune response was significantly greater after breakthrough-infection than in response to the 4th dose of BNT162b2.

Keywords: BNT162b2 vaccine; SARS-CoV-2; cancer patient.

Figure 1

Analysis of specific anti-SARS-CoV-2 IgG levels in fully vaccinated (third BNT162b2 dose) oncology patients as compared to patients receiving a 4th BNT162b2 dose or experiencing a breakthrough infection. (A) Quantification of IgG levels against the spike receptor-binding domain (RBD) of SARS-CoV-2 in patients vaccinated only with the 3rd-BNT162b2 dose (Control; n = 22), patients vaccinated with the second BNT162b2 booster (4th-BNT162b2 dose; n = 11), or patients who experienced Covid-19 breakthrough infections (breakthrough infection; n = 9). Blood test indicates IgG levels at baseline (after the 3rd-BNT162b2 dose), and blood test-2 indicates IgG levels after breakthrough infection, the 4th-BNT162b2-dose or matched or a corresponding time range for the Control group. (B) Comparison of levels of anti-SARS-CoV-2 IgG measured during the second blood test (blood test-2) is presented as the median and interquartile range (IQR) (see also Supplementary Table S1). Significant differences (P < .05) are indicated using horizontal solid lines.