Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Fendler, Annika; Au, Lewis; Shepherd, Scott T.C.; Byrne, Fiona; Cerrone, Maddalena; Boos, Laura Amanda; Rzeniewicz, Karolina; Gordon, William; Shum, Ben; Gerard, Camille L.; Ward, Barry; Xie, Wenyi; Schmitt, Andreas M.; Joharatnam-Hogan, Nalinie; Cornish, Georgina H.; Pule, Martin; Mekkaoui, Leila; Ng, Kevin W.; Carlyle, Eleanor; Edmonds, Kim; Del Rosario, Lyra; Sarker, Sarah; Lingard, Karla; Mangwende, Mary; Holt, Lucy; Ahmod, Hamid; Stone, Richard; Gomes, Camila; Flynn, Helen R.; Agua-Doce, Ana; Hobson, Philip; Caidan, Simon; Howell, Michael; Wu, Mary; Goldstone, Robert; Crawford, Margaret; Cubitt, Laura; Patel, Harshil; Gavrielides, Mike; Nye, Emma; Snijders, Ambrosius P; MacRae, James I; Nicod, Jerome; Gronthoud, Firza; Shea, Robyn L.; Messiou, Christina; Cunningham, David; Chau, Ian; Starling, Naureen; Turner, Nicholas; Welsh, Liam; van As, Nicholas; Jones, Robin L.; Droney, Joanne; Banerjee, Susana; Tatham, Kate C.; Jhanji, Shaman; O’Brien, Mary; Curtis, Olivia; Harrington, Kevin; Bhide, Shreerang; Bazin, Jessica; Robinson, Anna; Stephenson, Clemency; Slattery, Tim; Khan, Yasir; Tippu, Zayd; Leslie, Isla; Gennatas, Spyridon; Okines, Alicia; Reid, Alison; Young, Kate; Furness, Andrew J.S.; Pickering, Lisa; Gandhi, Sonia; Gamblin, Steve; Swanton, Charles; Nicholson, Emma; Kumar, Sacheen; Yousaf, Nadia; Wilkinson, Katalin A.; Swerdlow, Anthony; Harvey, Ruth; Kassiotis, George; Larkin, James; Wilkinson, Robert J.; Turajlic, Samra

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.