CoVigi phase IV multicentric trial evaluating COVID-19 vaccination effectiveness, safety, and immune response dynamics: SARS-CoV-2-specific antibody and T-cell response focused on patients with gastrointestinal tumors

Solid cancer patients are at high risk of a more severe course of COVID-19, especially those undergoing active anti-cancer therapy causing immunosuppression. Vaccination is still the only option to prevent serious events associated with SARS-CoV-2 infection. We aim to assess adverse effects, efficacy, and immune response against SARS-CoV-2 in cancer patients, focusing on comparison with healthy volunteers and possible interfering therapy.

CoVigi is a prospective open-label non-randomized multicentric phase 4 clinical study (EudraCT 2021-000566-14) enrolling patients on anti-cancer treatment (chemotherapy±monoclonal antibodies, monoclonal antibodies, checkpoint inhibitors, oral targeted treatment, and curative radiotherapy), and healthy volunteers. Data on vaccination side effects, the onset and course of COVID-19, and quantitative analysis of anti-S and anti-N SARS-CoV-2 antibodies (Roche) and SARS-CoV-2 specific T-cell response evaluated by IFN-gamma-release assay (Qiagen) and SARS-CoV-2 specific CD69 lymphocyte upregulation are recorded as follows: at the baseline (prior to the vaccination; V1), prior to the 2nd dose (V2), 4-8 weeks (V3), 3, 6, 12, 18 and 24 months (V4-8) after the 1st dose. Only subjects treated with vaccines from Pfizer-BioNTech were included in this analysis.

During recruitment between April and September 2021, 204 solid cancer patients (91 breast, 45 gastrointestinal, 34 genitourinary, 15 head and neck or lung cancers, 13 melanoma, and 6 others) and 73 healthy volunteers were enrolled for this analysis. For GI patients, the median age was 59 years, 53% were men, and most frequently were treated with CT (62%) or CT+mAb (24%). The V1 data show that 36% of GI patients had detectable levels of anti-SARS-CoV-2 antibodies prior to vaccination (equally to healthy volunteers, insignificantly more than other cancers), and only half of them referred to COVID-19 in medical history. In the SARS-CoV-2 recovered cohort, median values for anti-S antibodies and T-cell response (upon both CD4 and CD8 stimulation) in V1 were 99.5 vs. 82.7 U/ml (p=0.768) and 0.04 vs. 0.05 pg/ml (p=0.846) for GI patients and reference cohort, respectively. The median values increased to 22,955 vs. 55,595 U/ml (p=0.008) and 0.40 vs. 1.08 pg/ml (p=0.004) after the 2nd vaccine dose (V3), and diminished to 2,648 vs. 5,400 U/ml (p=0.050) and 0.17 vs. 0.42 pg/ml (p=0.030) in the follow-up visit (V5), for GI patients and reference cohort, respectively. In the SARS-CoV-2 naïve cohort, immune response remained substantially lower. The median values increased to 207 vs. 13,790 U/ml (p < 0.001) and 0.53 vs. 0.46 pg/ml (p= 0.573) after the 2nd vaccine dose (V3), and diminished to 210 vs. 1,526 U/ml (p < 0.001) and 0.11 vs. 0.12 pg/ml (p=0.449) in the follow-up visit (V5), for GI patients and reference cohort, respectively. Moreover, in SARS-CoV-2 naïve, 52% of GI patients revealed seroconversion after 1st dose (V2), 86% within three weeks after 2nd dose, and 100% after the 3 months from initiation. In contrast, all health volunteers revealed seroconversion after 1st dose.

The immune response was higher in healthy volunteers compared to GI patients and was substantially influenced by pre-vaccination SARS-CoV-2 infection. Post-vaccination response SARS-CoV-2 recovered cancer patients remained substantially higher than SARS-CoV-2 naïve cancer patients.

EudraCT 2021-000566-14.

Masaryk University.

CZECRIN LM2018128, Roche Diagnostics, MHCZ/DRO (MMCI00209805, FNBr 65269705).

All authors have declared no conflicts of interest.