COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma. Issue 7 (28th July 2021)

• Record Type: Journal Article
• Authors: Gaitzsch, Erik; Passerini, Verena; Khatamzas, Elham; Strobl, Carolin D.; Muenchhoff, Maximilian; Scherer, Clemens; Osterman, Andreas; Heide, Michael; Reischer, Anna; Subklewe, Marion; Leutbecher, Alexandra; Tast, Benjamin; Ruhle, Adrian; Weiglein, Tobias; Stecher, Stephanie-Susanne; Stemmler, Hans J.; Dreyling, Martin; Girl, Philipp; Georgi, Enrico; Wölfel, Roman; Mateyka, Laura; D'Ippolito, Elvira; Schober, Kilian; Busch, Dirk H.; Kager, Juliane; Spinner, Christoph D.; Treiber, Matthias; Rasch, Sebastian; Lahmer, Tobias; Iakoubov, Roman; Schneider, Jochen; Protzer, Ulrike; Winter, Christof; Ruland, Jürgen; Quante, Michael; Keppler, Oliver T.; von Bergwelt-Baildon, Michael; Hellmuth, Johannes; Weigert, Oliver;
• Is Part Of: HemaSphere. Volume 5:Issue 7(2021)
• Page Start: e603
• Publication Date: 2021-07-28
• Subjects: Hematology -- Periodicals; 616.15005
• DOI: 10.1097/HS9.0000000000000603
• Languages: English
• ISSNs: 2572-9241

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : 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.