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Anti-SARS-CoV-2 antibody containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19 via increased neutralizing antibody activity. A randomized clinical trial
Claudia M Denkinger; Maike Janssen; Ulrike Schaekel; Julia Gall; Albrecht Leo; Patrick Stelmach; Stefan Fabian Weber; Johannes Krisam; Lukas Baumann; Jacek Stermann; Uta Merle; Markus A Weigand; Christian Nusshag; Lars Bullinger; Jens-Florian Schrezenmeier; Martin Bornhaeuser; Nael Alakel; Oliver Witzke; Timo Wolf; Maria JGT Vehreschild; Stefan Schmiedel; Marylyn M Addo; Felix Herth; Michael Kreuter; Phil-Robin Tepasse; Bernd Hertenstein; Mathias Haenel; Anke Morgner; Michael Kiehl; Olaf Hopfer; Mohammad-Amen Wattad; Carl C Schimanski; Cihan Celik; Thorsten Pohle; Matthias Ruhe; Winfried V Kern; Anita Schmitt; Hanns-Martin Lorenz; Margarida Souto-Carneiro; Mary Gaeddert; Niels Halama; Stefan Meuer; Hans-Georg Kraeusslich; Barbara Mueller; Paul Schnitzler; Sylvia Parthe; Ralf Bartenschlager; Martina Gronkowski; Jennifer Klemmer; Michael Schmitt; Peter Dreger; Katharina Kriegsmann; Richard F Schlenk; Carsten Mueller-Tidow.
Afiliação
  • Claudia M Denkinger; Division of Infectious Disease and Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany, German Center for
  • Maike Janssen; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Ulrike Schaekel; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Julia Gall; NCT-Trial Center, National Center of Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany
  • Albrecht Leo; Institute for Clinical Transfusion Medicine and Cell Therapy Heidelberg, Heidelberg
  • Patrick Stelmach; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Stefan Fabian Weber; Division of Infectious Disease and Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany
  • Johannes Krisam; Institute for Medical Biometry and Informatics, Ruprecht-Karls University Heidelberg, Heidelberg, Germany
  • Lukas Baumann; Institute for Medical Biometry and Informatics, Ruprecht-Karls University Heidelberg, Heidelberg, Germany
  • Jacek Stermann; Institute for Medical Biometry and Informatics, Ruprecht-Karls University Heidelberg, Heidelberg, Germany
  • Uta Merle; Department of Internal Medicine IV, Heidelberg University Hospital, Heidelberg, Germany
  • Markus A Weigand; Department of Anaesthesiology, Heidelberg University Hospital, Heidelberg, Germany
  • Christian Nusshag; Department of Nephrology, University of Heidelberg, Heidelberg, Germany
  • Lars Bullinger; Department of Hematology, Oncology and Tumor Immunology, Charite University Medicine, Campus Virchow Clinic, Berlin, Germany
  • Jens-Florian Schrezenmeier; Department of Hematology, Oncology and Tumor Immunology, Charite University Medicine, Campus Virchow Clinic, Berlin, Germany
  • Martin Bornhaeuser; Department of Internal Medicine I, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany
  • Nael Alakel; Department of Internal Medicine I, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany
  • Oliver Witzke; Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Germany
  • Timo Wolf; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
  • Maria JGT Vehreschild; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
  • Stefan Schmiedel; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Marylyn M Addo; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; University Medical Center Hamburg-Eppendorf, Institute for Infection R
  • Felix Herth; Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany
  • Michael Kreuter; Center for Interstitial and Rare Lung Diseases, Thoraxklinik, University of Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany
  • Phil-Robin Tepasse; Department of Medicine B, Gastroenterology and Hepatology, University Hospital Muenster, Muenster, Germany
  • Bernd Hertenstein; Medical Department I, Klinikum Bremen-Mitte, Bremen, Germany
  • Mathias Haenel; Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
  • Anke Morgner; Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
  • Michael Kiehl; Department I of Internal Medicine, Frankfurt (Oder) General Hospital, Frankfurt/Oder, Germany
  • Olaf Hopfer; Department I of Internal Medicine, Frankfurt (Oder) General Hospital, Frankfurt/Oder, Germany
  • Mohammad-Amen Wattad; Department of Hematology, Oncology, Palliative Care and Stem Cell Transplantation, Klinikum Hochsauerland GmbH, Meschede, Germany
  • Carl C Schimanski; Department of Internal Medicine II, Klinikum Darmstadt GmbH, Darmstadt, Germany
  • Cihan Celik; Department of Internal Medicine II, Klinikum Darmstadt GmbH, Darmstadt, Germany
  • Thorsten Pohle; Department of Internal Medicine I, Klinikum Herford, Germany
  • Matthias Ruhe; Department of Internal Medicine I, Klinikum Herford, Germany
  • Winfried V Kern; Department of Medicine II, Division of Infectious Diseases and Travel Medicine, University Medical Centre Freiburg, Freiburg, Germany
  • Anita Schmitt; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Hanns-Martin Lorenz; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Margarida Souto-Carneiro; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Mary Gaeddert; Division of Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany
  • Niels Halama; Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany; Department of Translational Immunothera
  • Stefan Meuer; Institute for Clinical Transfusion Medicine and Cell Therapy Heidelberg, Heidelberg
  • Hans-Georg Kraeusslich; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Barbara Mueller; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Paul Schnitzler; Barbara.Mueller@med.uni-heidelberg.de
  • Sylvia Parthe; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Ralf Bartenschlager; Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Martina Gronkowski; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Jennifer Klemmer; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Michael Schmitt; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Peter Dreger; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Katharina Kriegsmann; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
  • Richard F Schlenk; NCT-Trial Center, National Center of Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany Department of Interna
  • Carsten Mueller-Tidow; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22280850
ABSTRACT
Cancer patients are at high risk of severe COVID-19 with high morbidity and mortality. Further, impaired humoral response renders SARS-CoV-2 vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a multicenter trial (https//www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE) in hospitalized patients with severe COVID-19 within four risk groups (1, cancer; 2, immunosuppression; 3, lab-based risk factors; 4, advanced age) randomized to standard of care (CONTROL) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (PLASMA). For the four groups combined, PLASMA did not improve clinically compared to CONTROL (HR 1.29; p=0.205). However, cancer patients experienced shortened median time to improvement (HR 2.50, p=0.003) and superior survival in PLASMA vs. CONTROL (HR 0.28; p=0.042). Neutralizing antibody activity increased in PLASMA but not in CONTROL cancer patients (p=0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcome in cancer patients unable to intrinsically generate an adequate immune response.
Licença
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Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Experimental_studies / Estudo prognóstico / Rct Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Experimental_studies / Estudo prognóstico / Rct Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
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