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.
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.