HemaSphere (Jul 2021)

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

  • Erik Gaitzsch,
  • Verena Passerini,
  • Elham Khatamzas,
  • Carolin D. Strobl,
  • Maximilian Muenchhoff,
  • Clemens Scherer,
  • Andreas Osterman,
  • Michael Heide,
  • Anna Reischer,
  • Marion Subklewe,
  • Alexandra Leutbecher,
  • Benjamin Tast,
  • Adrian Ruhle,
  • Tobias Weiglein,
  • Stephanie-Susanne Stecher,
  • Hans J. Stemmler,
  • Martin Dreyling,
  • Philipp Girl,
  • Enrico Georgi,
  • Roman Wölfel,
  • Laura Mateyka,
  • Elvira D’Ippolito,
  • Kilian Schober,
  • Dirk H. Busch,
  • Juliane Kager,
  • Christoph D. Spinner,
  • Matthias Treiber,
  • Sebastian Rasch,
  • Tobias Lahmer,
  • Roman Iakoubov,
  • Jochen Schneider,
  • Ulrike Protzer,
  • Christof Winter,
  • Jürgen Ruland,
  • Michael Quante,
  • Oliver T. Keppler,
  • Michael von Bergwelt-Baildon,
  • Johannes Hellmuth,
  • Oliver Weigert

Journal volume & issue
Vol. 5, no. 7
p. e603


Read online

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.