Longitudinal Study of SARS-CoV-2 Vaccinations and Infections in Patients with Gastrointestinal Cancer: Stabilizing Immune Responses and Neutralizing Emerging Variants with Variant-Adapted Antigen Exposures

This longitudinal study examined how active gastrointestinal (GI) cancer types affect immune responses to SARS-CoV-2, focusing on the ability to neutralize the Omicron variants. Patients with GI cancer (<i>n</i> = 168) were categorized into those with hepatocellular carcinoma, hepatic metastatic GI cancer, non-hepatic metastatic GI cancer, and two control groups of patients with and without underlying liver diseases. Humoral and cellular immune responses were evaluated before and after Omicron antigen exposures. In the pre-Omicron era, humoral SARS-CoV-2 immunity decreased after three antigen contacts without further antigen exposure. While Omicron neutralization was significantly lower than wildtype neutralization (<i>p</i> < 0.01), Omicron infections were yet mild to moderate. Additional Omicron exposures improved IgG levels (<i>p</i> < 0.01) and Omicron neutralization (<i>p</i> < 0.01). However, this effect was significantly less intense in patients with active GI cancer, particularly in patients with pancreaticobiliary neoplasms (PBN; <i>p</i> = 0.04), with underlying immunodeficiency (<i>p</i> = 0.05), and/or under conventional chemotherapy (<i>p</i> = 0.05). Pre-Omicron SARS-CoV-2 immunity prevented severe clinical courses of infections with Omicron variants in patients with GI cancer. However, in patients with PBN, with underlying immunodeficiency, and/or under conventional chemotherapy initial contacts with Omicron antigens triggered only reduced immune responses. Thus, subgroups could be identified for whom booster vaccinations are of special clinical significance.