SARS-CoV-2 Vaccine Immunogenicity in Patients with Gastrointestinal Cancer Receiving Systemic Anti-Cancer Therapy

Abstract

Introduction: Patients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination.

Materials and methods: Between September 2020 and April 2021, patients with cancer undergoing chemotherapy were enrolled. At baseline (day 0), days 28, 56, and 84, we assessed serum antibodies to SARS-CoV-2 spike (anti-S) and anti-nucleocapsid (anti-NP) and concomitantly assessed virus neutralization using a pseudovirus neutralization assay. Patients received either the Pfizer/BioNTech BNT162b2, or the Oxford/AstraZeneca ChAdOx1 vaccine.

Results: All 152 patients enrolled had a prior diagnosis of cancer; colorectal (n = 80, 52.6%), oesophagogastric (n = 38, 25.0%), and hepato pancreatic biliary (n = 22, 12.5%). Nearly all were receiving systemic anti-cancer therapy (99.3%). Of the 51 patients who did not receive a vaccination prior to, or during the study, 5 patients had detectable anti-NP antibodies. Ninety-nine patients received at least one dose of vaccine prior to, or during the study. Within 19 days following the first dose of vaccine, 30.0% had anti-S detected in serum which increased to 70.2% at days 20-39. In the 19 days following a second dose, anti-S positivity was 84.2% (32/38). However, pseudovirus neutralization titers (pVNT80) decreased from days 20 to 39.

Conclusion: Despite the immunosuppressive effects of chemotherapy, 2 doses of SARS-CoV-2 vaccines are able to elicit a protective immune response in patients' ongoing treatment for gastrointestinal cancers. Decreases in pseudoviral neutralization were observed after 20-39 days, re-affirming the current recommendation for vaccine booster doses.

Clinical trial registration number: NCT04427280.

Keywords: COVID-19; SARS-CoV-2; anti-spike; chemotherapy; gastrointestinal cancer; immunity; pseudovirus; vaccines.

© The Author(s) 2022. Published by Oxford University Press.

Figures

Figure 1.

CONSORT diagram of the CARDS study. *Patients RM5287107, RF5287069 withdrew before blood samples were taken. Abbreviations: D0, baseline; D28, day 28; D56, day 56; D84, day 84.

Figure 2.

Longitudinal analysis of SARS-CoV-2 vaccine immunogenicity relative to the 1st vaccine dose. Box plot of Anti-S index values (A) and pseudovirus neutralisation (titre 1/40) in all vaccinated patients (B) at time periods relative to the date of 1st vaccine dose. Each data point represents a serum sample. Solid horizontal lines denote the median and boxes represent the interquartile range. Samples from patients with positive nucleocapsid results are marked in red and negative in blue. Positivity thresholds are denoted by dotted lines (anti-S > 1.0, pVNT(1/40) > 0.5). Abbreviation: anti-S, anti-spike antibody.

Figure 3.

Longitudinal analysis of SARS-CoV-2 vaccine immunogenicity following 2nd vaccine dose. Box plot of anti-S index values (A) and pseudovirus neutralisation (titre 1/40) in all vaccinated patients (B) at time periods relative to the date of 2nd SARS-CoV-2 vaccine dose. Each data point represents a serum sample. Solid lines denote the median and boxes represent the interquartile range. Samples from patients with positive nucleocapsid results are marked in red and negative in blue. Prespecified positivity thresholds are denoted by dotted lines (anti-S > 1.0, anti-S > 1.0, pVNT(1/40) > 0.5).

Figure 4.

Box plots of pVNT80 neutralization titers after the 2nd dose of SARS-CoV-2 vaccine. A logarithmic scale was used for neutralization titre. Each data point represents a serum sample. Solid lines denote the median and boxes represent the interquartile range. Samples from patients with positive nucleocapsid results are marked in red and negative in blue.