COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma

Gaitzsch, E., Passerini, V., Khatamzas, E., Strobl, C.D., Muenchhoff, M., Scherer, C., Osterman, A., Heide, M., Reischer, A., Subklewe, M., Leutbecher, A., Tast, B., Ruhle, A., Weiglein, T., Stecher, S.S., Stemmler, H.J., Dreyling, M., Girl, P., Georgi, E., Wolfel, R., Mateyka, L., D'Ippolito, E., Schober, K., Busch, D.H., Kager, J., Spinner, C.D., Treiber, M., Rasch, S., Lahmer, T., Iakoubov, R., Schneider, J., Protzer, U., Winter, C., Ruland, J., Quante, M., Keppler, O.T., von Bergwelt-Baildon, M., Hellmuth, J., Weigert, O. (2021). Hemasphere 5, e603.

DOI:10.1097/HS9.0000000000000603(link is external)


The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19. We performed detailed clinical analyses, in-depth cellular and molecular immune profiling, and comprehensive virological studies in 12 patients with available biospecimens. B-cell depleted lymphoma patients had more severe and protracted clinical course (median hospitalization 88 versus 17 d). All patients actively receiving immunochemotherapy (n = 5) required ICU support including long-term mechanical ventilation. Neutrophil recovery following granulocyte colony stimulating factor stimulation coincided with hyperinflammation and clinical deterioration in 4 of the 5 patients. Immune cell profiling and gene expression analysis of peripheral blood mononuclear cells revealed early activation of monocytes/macrophages, neutrophils, and the complement system in B-cell depleted lymphoma patients, with subsequent exacerbation of the inflammatory response and dysfunctional interferon signaling at the time of clinical deterioration of COVID-19. Longitudinal immune cell profiling and functional in vitro assays showed SARS-CoV-2-specific CD8+ and CD4+ T-effector cell responses. Finally, we observed long-term detection of SARS-CoV-2 in respiratory specimens (median 84 versus 12 d) and an inability to mount lasting SARS-CoV-2 antibody responses in B-cell depleted lymphoma patients. In summary, we identified clinically relevant particularities of COVID-19 in lymphoma patients receiving B-cell depleting immunochemotherapies.