Predicting COVID-19 infection risk in lymphoma by immune monitoring

Wijaya, R., Campbell, N., Johnson, M., Stuart, B., Kelly, A., Tipler, N., Coleman, A., Turaj, A., Menne, T., Ahearne, M., Willimott, V., Al-Naeeb, A. Bowzyk, Fox, C.P., Collins, G.P., O'Callaghan, A., Davies, A.J., Goldblatt, D. and Lim, S.H. (2023) Predicting COVID-19 infection risk in lymphoma by immune monitoring. Hematological Oncology, 41 (S2), 606-607. (doi:10.1002/hon.3164_456).

Abstract

Introduction: patients with B-cell lymphoma have poorer antibody responses to COVID-19 vaccines compared to patients with other malignancies. However, the immune responses are heterogeneous and its association with clinical outcomes are poorly understood. Here, we study the association between antibody and cellular responses with the outcomes from COVID-19 infection from the PROSECO study.

Methods: THE UK PROSECO study is a prospective observational cohort study evaluating COVID-19 vaccine response in people with lymphoma. Peripheral blood antibody titres (anti-spike (S) IgG by Mesoscale Discovery), antibody avidity (surface plasmon resonance) and IFNγ T-cell responses (ELISpot) against spike protein after two to four COVID-19 vaccines, and clinical outcomes data were collected.

Results: 524 patients (92 Hodgkin lymphoma, 180 aggressive B non-Hodgkin lymphoma (B-NHL), 234 indolent B-NHL and 18 peripheral T-cell lymphoma) were included: 334 (84·3%), 315 (79·5%) and 266 (67·1%) participants were eligible for post-two, three and four vaccine dose analysis, respectively. Breakthrough infections (BTI) occurred in 20 (5.9%), 40 (12.7%) and 36 (13.5%) participants after two, three and four vaccine doses. Of 96 participants with BTI, 12 (12.5%) needed hospitalisation. No deaths were observed due to COVID-19 infection. No differences were observed in T-cell responses between BTI and non-BTI groups, but 4/9 (44.5%) hospitalised BTI cases had undetectable cellular and antibody responses. There was no association between antibody titres and infection episodes after two vaccine doses, but antibody titres were associated with lower BTI risk after three or four vaccine doses on multivariable analysis. Intriguingly, the antibody threshold associated with infection risk was lower after four than three vaccine doses (41 vs. 820 BAU/mL). We also observed stronger antibody binding avidity to SARS-CoV-2 spike receptor-binding domain (RBD) proteins from Wuhan and Omicron BQ.1 variants, with increasing vaccine doses, i.e., fourth versus third dose: 10-fold increase (p: <0.01); fourth versus second dose:100-fold-increase than the second dose (p: <0.0001) (see Figure).

Conclusion: anti-S antibody titres can predict the risk of COVID-19 infection after three or more vaccine doses in patients with lymphoma. Repeated COVID-19 vaccination drives antibody affinity maturation and consequently improves the strength of antibody binding to virus spike proteins. Nearly half of participants who required hospitalisation for COVID-19 had undetectable antibody and cellular immunity to vaccination. Altogether, these data show the importance of booster vaccine doses and immune monitoring post COVID-19 vaccination to identify lymphoma patients who still continue to be at risk from severe COVID-19, and thus the best prophylactic and therapeutic strategies.

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Contributors

Author: N. Campbell

Author: A.J. Davies

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