Impact of Cancer Subtype and Cancer Therapy Exposures on SARS-CoV-2 Outcomes in the Omicron and Subvariant Era.

Introduction: Amidst highly transmissible SARS-CoV-2 variants that continue to circulate in the community, individuals with cancer exhibit variations in immunity and susceptibility for reasons that remain poorly understood.

Methods: In a longitudinal cohort study with ongoing SARS-CoV-2 serological and outcomes surveillance, we examined adults receiving cancer treatment (cases, n = 229) or who were free of cancer and other major comorbidities (controls, n = 800), prior to the Omicron era onset and onwards (September 24, 2021-March 10, 2024). The main outcomes were longitudinal SARS-CoV-2 anti-spike receptor binding domain IgG (IgG-SRBD) antibody response and Omicron and subvariant infection frequency and severity.

Results: Among the 229 participants with cancer (age 66 ± 12 years, 51% female), the most prevalent subtypes included nonmelanoma skin (23%), breast (20%), and hematologic (18%). In mixed-effects linear models, hematologic cancer and B-cell targeted agents were associated with reduced longitudinal IgG-SRBD response (p < 0.05). In multivariable regression analyses, hematologic cancer (p = 0.037) and B-cell targeted agents (p = 0.030) were associated with increased frequency of new infections. The frequency of new infections resulting in moderate illness was increased in patients with active/recent cancer treatment (44%) versus healthy controls (10%; p < 0.001); there were no severe or critical infections. Patients with hematologic, breast, prostate, or skin cancer (p < 0.01), treated with local therapy (odds ratio [OR] 1.82; 95% confidence interval [CI] 1.05-3.15; p = 0.032), B-cell targeted therapy (OR 4.81; 95% CI 1.78-12.93; p = 0.002), or small molecule agents (OR 2.34; 95% CI 1.05-5.23; p = 0.037) were associated with increased infection severity.

Conclusions: Individuals with hematologic cancer or exposed to B-cell-targeted therapy had reduced humoral immunity and more frequent and severe infections. Active breast, prostate, or skin cancer, or treatment with local therapy or small molecule agents had elevated risk for more severe, but not more frequent, infections. Despite overall low rates of infection associated with lower respiratory disease, certain higher-risk cancer patients may benefit from further protective measures.