COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma
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 coho...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-07-01
|
| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000603 |
| _version_ | 1797282402970632192 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Erik Gaitzsch |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:12:26Z |
| format | Article |
| id | doaj.art-094ad305bd0d4e23983309dd91f61e83 |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-03-07T17:12:26Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-094ad305bd0d4e23983309dd91f61e832024-03-03T00:43:22ZengWileyHemaSphere2572-92412021-07-0157e60310.1097/HS9.0000000000000603202107000-00015COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell LymphomaErik Gaitzsch0Verena Passerini1Elham Khatamzas2Carolin D. Strobl3Maximilian Muenchhoff4Clemens Scherer5Andreas Osterman6Michael Heide7Anna Reischer8Marion Subklewe9Alexandra Leutbecher10Benjamin Tast11Adrian Ruhle12Tobias Weiglein13Stephanie-Susanne Stecher14Hans J. Stemmler15Martin Dreyling16Philipp Girl17Enrico Georgi18Roman Wölfel19Laura Mateyka20Elvira D’Ippolito21Kilian Schober22Dirk H. Busch23Juliane Kager24Christoph D. Spinner25Matthias Treiber26Sebastian Rasch27Tobias Lahmer28Roman Iakoubov29Jochen Schneider30Ulrike Protzer31Christof Winter32Jürgen Ruland33Michael Quante34Oliver T. Keppler35Michael von Bergwelt-Baildon36Johannes Hellmuth37Oliver Weigert381 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany2 Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, LMU München, Germany4 COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU Munich, Germany2 Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, LMU München, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany3 German Center for Infection Research (DZIF), partner site Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany8 Department of Medicine II, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany9 Bundeswehr Institute of Microbiology, Munich, Germany9 Bundeswehr Institute of Microbiology, Munich, Germany9 Bundeswehr Institute of Microbiology, Munich, Germany10 Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany10 Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany10 Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany10 Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany11 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany12 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Munich, Germany12 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Munich, Germany11 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany11 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany11 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany11 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany3 German Center for Infection Research (DZIF), partner site Munich, Germany7 German Cancer Consortium (DKTK), Munich, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany7 German Cancer Consortium (DKTK), Munich, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany11 Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany2 Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, LMU München, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, GermanyThe 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.http://journals.lww.com/10.1097/HS9.0000000000000603 |
| spellingShingle | 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 COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma HemaSphere |
| title | COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma |
| title_full | COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma |
| title_fullStr | COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma |
| title_full_unstemmed | COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma |
| title_short | COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma |
| title_sort | covid 19 in patients receiving cd20 depleting immunochemotherapy for b cell lymphoma |
| url | http://journals.lww.com/10.1097/HS9.0000000000000603 |
| work_keys_str_mv | AT erikgaitzsch covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT verenapasserini covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT elhamkhatamzas covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT carolindstrobl covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT maximilianmuenchhoff covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT clemensscherer covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT andreasosterman covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT michaelheide covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT annareischer covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT marionsubklewe covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT alexandraleutbecher covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT benjamintast covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT adrianruhle covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT tobiasweiglein covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT stephaniesusannestecher covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT hansjstemmler covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT martindreyling covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT philippgirl covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT enricogeorgi covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT romanwolfel covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT lauramateyka covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT elviradippolito covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT kilianschober covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT dirkhbusch covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT julianekager covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT christophdspinner covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT matthiastreiber covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT sebastianrasch covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT tobiaslahmer covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT romaniakoubov covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT jochenschneider covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT ulrikeprotzer covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT christofwinter covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT jurgenruland covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT michaelquante covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT olivertkeppler covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT michaelvonbergweltbaildon covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT johanneshellmuth covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma AT oliverweigert covid19inpatientsreceivingcd20depletingimmunochemotherapyforbcelllymphoma |