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, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for 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 recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

Capturing adaptive immunity against SARS-CoV-2 in patients with cancer

“…1a). At the cellular level, the CAPTURE study found a lower proportion of patients with detectable virus-specific CD4 + T cells (81% of patients tested among those with solid cancer and 58% in hematological cancer) and CD8 + T cells (51% in solid cancer and 42% in hematological cancer) after natural infection 3 . This contrasts with healthy participants, who display rapid induction and then prolonged contraction of SARS-CoV-2-specific CD8 + T cells followed by the emergence of fully functional memory CD8 + T cells 5 .…”

“…The efficacy of the currently available vaccines in vulnerable patient populations is of critical medical importance and carries imminent implications for future vaccination strategies, including the evaluation of potential vaccination boosters. In this issue of Nature Cancer, Turajlic and colleagues characterize the specific adaptive immunity induced by full vaccination 2 or infection 3 with SARS-CoV-2, including by VOCs, in two reports from the CAPTURE (COVID-19 antiviral response in a pan-tumor immune monitoring) prospective study.…”

“…In these two elegant studies, the authors characterized the specific adaptive immunity against SARS-CoV-2 in patients with solid and hematological malignancies. Their first important finding is that natural infection and vaccination induce different immune profiles in people with solid versus hematological cancers 2,3 . Indeed, in line with previous studies 4 , they found that most patients with solid cancers have detectable S1-specific immunoglobulin G molecules, neutralizing antibodies and virus-specific T cell responses following natural infection and/or vaccination.…”

“…In comparison, individuals with hematological malignancies show weaker cellular and humoral immune responses. Importantly, patients with either solid or hematological cancers show impaired immune responses compared to the general population, as indicated by lower seroconversion rates following natural infection or vaccination 2,3 (Fig. 1a).…”

“…The authors' second important observation in these two studies is the impact of specific cancer subtypes on the status of the adaptive immune system after natural infection or vaccination 2,3 . For example, leukemia is associated with impaired T cell responses, whereas patients with lymphoma display low antibody titers (Fig.…”