ABSTRACT
Background: Patients with cancer are at increased risk of severe outcomes from COVID-19. Understanding the impact of SARS-CoV-2 infection and vaccination induced-immunity is an area of unmet need. Methods: CAPTURE (NCT03226886) is a prospective longitudinal cohort study of COVID-19 vaccine or SARS-CoV-2 infection-induced immunity. SARS-CoV-2 infections were confirmed by RT-PCR and ELISA. Neutralising antibody titres (NAbT) against wild-type (WT) SARS-CoV-2 and variants of concern (VOC;Alpha, Beta, Delta) and SARS-CoV-2 specific T-cells (SsT-cells) were quantified. Results: 118 patients (89% solid malignancy, [SM]) were SARS-CoV-2-positive (median follow-up: 154 days). 85% patients were symptomatic;2 died of COVID-19. 82% had S1-reactive antibodies, of whom 89% had neutralising antibodies (NAbs);NAbT were lower against all VOCs. While S1-reactive antibody levels declined over time, NAbT remained stable up to 329 days. Most patients had detectable SsT-cells (76% CD4+, 52% CD8+). Haematological malignancy (HM) patients had impaired immune responses that were disease and treatment-specific (anti-CD20), but with evidence suggestive of compensation from T-cells. 585 patients were evaluated following 2 doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after 2 doses were 85% and 54% in patients with SM and HM, respectively. A lower proportion of patients had detectable NAbs against SARS-CoV-2 VOC (Alpha 62%, Beta 54%, Delta 49%) vs WT (84%), with corresponding significantly lower NAbT. Patients with HM were more likely to have an undetectable NAb and had lower NAbT vs solid malignancies to both WT and VOCs. Seroconversion showed poor concordance with NAbTs against VOCs. Prior SARS-CoV-2 infection boosted NAbT including against VOCs. Anti-CD20 treatment was associated with severely diminished NAbTs. Vaccine-induced T-cell responses were detected in 80% of patients, with no differences between vaccines or cancer types. Conclusions: Patients with HM had blunted humoural responses to infection and vaccination, particularly against VOCs, but preserved cellular responses might contribute to protection. Our results lend support to prioritisation of all cancer patients for further booster vaccination. Clinical trial identification: NCT03226886. Legal entity responsible for the study: The Royal Marsden NHS Foundation Trust. Funding: The Royal Marsden Charity;The National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at the Royal Marsden Hospital and Institute for Cancer Research (ICR). Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Introduction: Certain retrospective and registry-based studies have indicated a higher risk of COVID-19 adverseoutcomes in cancer, but a detailed understanding of the immune response in cancer patients and the impact ofcancer therapy is needed. CAPTURE is a pan-cancer, prospective longitudinal study established in response to theunique challenges of SARS-CoV-2 pandemic for the care of cancer patients. Experimental Procedures: CAPTURE is a multicenter, UK-based longitudinal cohort study that commencedrecruitment in May 2020. Study participants are recruited from a broad range of cancer types and cancerinterventions and irrespective of their SARS-CoV-2 status, in order to capture both the nominator and thedenominator. In addition to cancer patients, the study participants also include health care workers (HCW) for thepurpose of studying transmission dynamics. Detailed clinical, epidemiologic, and demographic data are collectedfrom all participants alongside a range of biologic samples that underpin case definitions and will facilitate immunemonitoring. All participants will be followed up longitudinally for up to five years. Results: The overarching aim is to establish a prospective and unbiased understanding of the susceptibility andmorbidity of COVID-19 in cancer patients and the patterns of viral nosocomial transmission. We will follow uppatients long-term to understand the extent and duration of immunity and how immunity is impacted by cancer type, stage, and therapy. Our comprehensive sampling will help to draw a detailed picture of immune response to SARS-CoV-2 in cancer patients by monitoring active infection, antibody response, and T-cell activation, supplemented bydetailed immunophenotyping, transcriptome, TCR/BCR sequencing, and germline profiling for HLA typing andidentification of disease-associated polymorphisms. Finally, while there is a well-established correlation of circulatingcytokine levels and Covid-19 severity, CAPTURE will identify early indicators of a maladapted inflammatoryresponse in cancer patients by cytokine and chemokine profiling to establish early biomarkers of disease severity.Within the first month, we have recruited 95 participants (54% cancer patients, 46% HCWs) with matching swabs, plasma, PBMC, and whole blood for RNA sequencing. Two longitudinal samples were collected on average. Resultsfrom antigen and antibody profiling within this cohort will be presented at the meeting. Conclusion: CAPTURE will provide a detailed understanding of the interaction between immune response toSARS-CoV-2, cancer, and cancer treatments. Results will be informative in a wider health care context in order tominimize harm and maximize cancer outcomes in a sustainable manner. Furthermore, given inherent and iatrogenicdefects in discreet immune cell subsets, this is a key patient cohort to inform a wider understanding of the immuneresponse to SARS-CoV-2.