Impaired seroconversion after SARS-CoV-2 mRNA vaccines in patients with solid tumours receiving anticancer treatment

Abstract

Background: Patients with solid tumours have high COVID-19 mortality. Limited and heterogeneous data are available regarding the immunogenicity of SARS-CoV-2 mRNA vaccines in this population.

Methods and findings: This is a prospective, single-centre cohort study aiming at evaluating seroconversion in terms of anti-spike antibodies in a population of patients with solid tumours undergoing cancer therapy within 2 months before the second vaccine dose, as compared with a cohort of controls. Subjects who were not SARS-CoV-2 naïve were excluded, and 171 patients were included in the final study population (150 vaccinated with BNT162b2, 87.7%; 21 with mRNA-1273, 12.3%) and compared with 2406 controls. The median follow-up time from the second dose of vaccination was 30 days (12-42; IQR: 26-34). Most patients had metastatic disease (138, 80.7%). Seroconversion rate was significantly lower in cancer patients than in controls (94.2% versus 99.8%, p < 0.001). At univariate logistic regression analysis, Odds ratio (OR) for seroconversion was also reduced in older individuals (>70 years). A multivariate logistic model confirmed cancer as the only significant variable in impairing seroconversion (OR 0.03, p < 0.001). In the cancer population, a multivariate analysis among clinical variables, including the type of cancer treatment, showed ECOG PS > 2 as the only one of impact (OR 0.07, p = 0.012).

Conclusions: There is a fraction of 6% of patients with solid tumours undergoing cancer treatment, mainly with poorer performance status, who fail to obtain seroconversion after SARS-CoV-2 mRNA vaccines. These patients should be considered for enhanced vaccination strategies and carefully monitored for SARS-CoV-2 infection during cancer treatment.

Keywords: COVID-19; Cancer; Chemotherapy; Immunogenicity; Immunotherapy; Seroconversion; Vaccine.

Fig. 1

Consort diagram. Flow diagram showing the selection process of cancer patients (A) and healthcare workers as control cohort (B). Keys: Anti-N IgG = anti-nucleocapsid immunoglobulin; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Fig. 2

Distribution of anti-S antibody titer according to age in cancer and control cohorts. The scatter plot displays anti-S Ab titer (y-axis, log scale) versus age (x-axis) in patients with titer under the essay upper limit of detection (2080 BAU/ml), with marginal density distribution on right and top, respectively; the red line shows the seroconversion limit (33.8 BAU/mL) of the essay. Keys: Ab = antibody; anti-S = anti-spike; BAU = binding arbitrary units; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Fig. 3

Multivariate analysis of clinical variables in the whole study population. The forest plot shows odds ratios for seroconversion, according to age, BMI, gender and group (cancer versus control cohort). Keys: BMI = body mass index.