ABSTRACT
CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wild-type (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T-cell responses were detected in 80% of patients, and were comparable between vaccines or cancer types. Our results have implications for the management of cancer patients during the ongoing COVID-19 pandemic.
Subject(s)
Neoplasms , Hematologic Neoplasms , COVID-19ABSTRACT
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.
Subject(s)
COVID-19 , Hematologic Neoplasms , NeoplasmsABSTRACT
We present a case of cytokine release syndrome (CRS) that occurred five days after vaccination with BTN162b2 (tozinameran), an mRNA COVID-19 vaccine, in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-y/IL-2R/IL-18/IL-16/IL-10), and steroid responsiveness.
Subject(s)
Thrombocytopenia , COVID-19 , Colorectal NeoplasmsABSTRACT
There is a pressing need to characterise the nature, extent and duration of immune response to SARS-CoV-2 in cancer patients and inform risk-reduction strategies and preserve cancer outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer patients and healthcare workers (HCWs) integrating longitudinal immune profiling and clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs from 144 cancer patients and 73 HCWs and correlated with >200 clinical variables. In patients with solid cancers and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2 were detectable five months post-infection. SARS-CoV-2-specific T-cell responses were detected, and CD4+ T-cell responses correlated with S1 antibody levels. Patients with haematological malignancies had impaired but partially compensated immune responses. Overall, cancer stage, disease status, and therapies did not correlate with immune responses. These findings have implications for understanding individual risks and potential effectiveness of SARS-CoV-2 vaccination in the cancer population.
Subject(s)
Neoplasms , Hematologic NeoplasmsABSTRACT
Since the beginning of the global SARS-CoV-2 pandemic, there have been a number of efforts to understand the mutations and clusters of genetic lines of the SARS-CoV-2 virus. Until now, phylogenetic analysis methods have been used for this purpose. Here we show that Principal Component Analysis (PCA), which is widely used in population genetics, can not only help us to understand existing findings about the mutation processes of the virus, but can also provide even deeper insights into these processes while being less sensitive to sequencing gaps. Here we describe a comprehensive analysis of a 46,046 SARS-CoV-2 genome sequence dataset downloaded from the GISAID database in June of this year. SummaryPCA provides deep insights into the analysis of large data sets of SARS-CoV-2 genomes, revealing virus lineages that have thus far been unnoticed.