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

Abstract

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.

Scottish COVID CAncer iMmunity Prevalence (SCCAMP) - a longitudinal study of patients with cancer receiving active anti-cancer treatment during the COVID-19 pandemic

“…Further, vaccination was associated with seroconversion rates of 85% after two doses, notably lower than the general population 11,12 . These and other data suggest that patients with solid-organ cancers do broadly develop an immune response to SARS-CoV-2, although it may be slightly reduced 10,11,13 . Other studies estimate an even lower or delayed immune response in this group of patients, although studies often include patients with haematological cancers, have early antibody testing strategies and may lack long-term follow-up 13–16 .…”

“…Many early studies could be influenced by a highly diverse definition of cancer and, importantly, changes in anti-cancer treatment policies during the pandemic 5 . More recent studies have evaluated the immune response of patients with cancer following SARS-CoV-2 infection and vaccination, with a wide variation in proposed responses owing to differences in study populations 10,11,13–15 . In contrast with much of the UK, the South East Scotland Cancer Network (SCAN), which comprises both hospitals reported here, had largely normalised SACT attendance rates by June/July 2020 (vs −31.2% in England and Northern Ireland) 23,24 .…”

“…Others have reported that patients with cancer may have delayed seroconversion 13,15 . Previously reported cohorts targeted patients with confirmed SARS-CoV-2 infection over a discrete period of time (both in terms of recruitment and antibody testing strategy) 10,11 . We may have been able to capture this with our longer follow up and denominator definition.…”

“…More recent studies have sought to characterise the immunological response to COVID-19 infection or immunisation in patients with cancer undergoing SACT with varying results. A study capturing data from February to May 2021, including 97 patients with solid-organ cancers and SARS-CoV-2 infection, suggested 89% of patients seroconverted in a cohort where 81% of patients had undergone SACT in the preceding 12 weeks 10 . Further, vaccination was associated with seroconversion rates of 85% after two doses, notably lower than the general population 11,12 .…”

COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety

“…T cell responses to vaccination appear to be less affected by ongoing treatment with B cell-depleting therapies 65,131 , highlighting that the ability of these patients to develop adaptive immunity is not completely disrupted. Furthermore, T cell responses, most importantly CD8 + responses, have been detected in patients with cancer receiving B cell-depleting therapies who subsequently developed COVID-19, even in the absence of humoral responses 135,136 , indicating that T cell responses alone can provide protection from severe outcomes. Ongoing graft-versus-host disease prophylaxis after allogeneic stem cell transplantation is the only scenario that predisposes to a reduced T cell response despite adequate virus-specific antibody levels.…”