Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial

被引：48

作者：

Denkinger, Claudia M. ^{[1
,2
]}

Janssen, Maike ^{[3
]}

Schaekel, Ulrike ^{[3
]}

Gall, Julia ^{[4
,5
]}

Leo, Albrecht ^{[6
]}

Stelmach, Patrick ^{[3
]}

Weber, Stefan F. ^{[1
]}

Krisam, Johannes ^{[7
]}

Baumann, Lukas ^{[7
]}

Stermann, Jacek ^{[7
]}

Merle, Uta ^{[8
]}

Weigand, Markus A. ^{[9
]}

Nusshag, Christian ^{[10
]}

Bullinger, Lars ^{[11
]}

Schrezenmeier, Jens-Florian ^{[11
]}

Bornhaeuser, Martin ^{[12
,13
]}

Alakel, Nael ^{[12
,13
]}

Witzke, Oliver ^{[14
]}

Wolf, Timo ^{[15
]}

Vehreschild, Maria J. G. T. ^{[15
]}

Schmiedel, Stefan ^{[16
]}

Addo, Marylyn M. ^{[16
,17
,18
]}

Herth, Felix ^{[19
,20
]}

Kreuter, Michael ^{[21
,22
]}

Tepasse, Phil-Robin ^{[23
]}

Hertenstein, Bernd ^{[24
]}

Haenel, Mathias ^{[25
]}

Morgner, Anke ^{[25
]}

Kiehl, Michael ^{[26
]}

Hopfer, Olaf ^{[26
]}

Wattad, Mohammad-Amen ^{[27
]}

Schimanski, Carl C. ^{[28
]}

Celik, Cihan ^{[28
]}

Pohle, Thorsten ^{[29
]}

Ruhe, Matthias ^{[29
]}

Kern, Winfried, V ^{[30
]}

Schmitt, Anita ^{[3
]}

Lorenz, Hanns-Martin ^{[3
]}

Souto-Carneiro, Margarida ^{[3
]}

Gaeddert, Mary ^{[1
]}

Halama, Niels ^{[31
,32
,33
]}

Meuer, Stefan ^{[6
]}

Kraeusslich, Hans-Georg ^{[34
]}

Mueller, Barbara ^{[34
]}

Schnitzler, Paul ^{[34
]}

Parthe, Sylvia ^{[34
]}

Bartenschlager, Ralf ^{[35
]}

Gronkowski, Martina ^{[3
]}

Klemmer, Jennifer ^{[3
]}

Schmitt, Michael ^{[3
]}

机构：

[1] Heidelberg Univ Hosp, Dept Infect Dis, Div Infect Dis & Trop Med, Heidelberg, Germany

[2] German Ctr Infect Res, Partner Site Heidelberg Univ Hosp, Heidelberg, Germany

[3] Heidelberg Univ Hosp, Dept Internal Med 5, Heidelberg, Germany

[4] Heidelberg Univ Hosp, NCT Trial Ctr, Natl Ctr Tumor Dis, Heidelberg, Germany

[5] German Canc Res Ctr, Heidelberg, Germany

[6] Inst Clin Transfus Med & Cell Therapy Heidelberg, Heidelberg, Germany

[7] Heidelberg Univ, Inst Med Biometry, Heidelberg, Germany

[8] Heidelberg Univ Hosp, Dept Internal Med 4, Heidelberg, Germany

[9] Heidelberg Univ Hosp, Dept Anesthesiol, Heidelberg, Germany

[10] Heidelberg Univ, Dept Nephrol, Heidelberg, Germany

[11] Charite Univ Med Berlin, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany

[12] Tech Univ Dresden, Dept Internal Med 1, Univ Hosp Dresden, Dresden, Germany

[13] Tech Univ Dresden, Fac Med Carl Gustav Carus, Dresden, Germany

[14] Univ Duisburg Essen, Univ Hosp Essen, West German Ctr Infect Dis, Dept Infect Dis, Essen, Germany

[15] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Dept Internal Med, Infect Dis, Frankfurt, Germany

[16] Univ Med Ctr Hamburg Eppendorf, Dept Med, Hamburg, Germany

[17] German Ctr Infect Res, Partner Site Hamburg Lubeck Borstel Riems, Hamburg, Germany

[18] Univ Med Ctr Hamburg Eppendorf, Inst Infect Res & Vaccine Dev, Hamburg, Germany

[19] Heidelberg Univ, Thoraxklin, Pneumol & Crit Care Med, Heidelberg, Germany

[20] Translat Lung Res Ctr, Heidelberg, Germany

[21] Heidelberg Univ, Ctr Interstitial & Rare Lung Dis, Thoraxklin, Pneumol & Crit Care Med, Heidelberg, Germany

[22] German Ctr Lung Res, Heidelberg, Germany

[23] Univ Hosp Muster, Dept Med Gastroenterol & Hepatol B, Munster, Germany

[24] Klinikum Bremen Mitte, Med Dept 1, Bremen, Germany

[25] Klinikum Chemnitz, Dept Internal Med 3, Chemnitz, Germany

[26] Frankfurt Oder Gen Hosp, Dept Internal Med 1, Frankfurt, Germany

[27] Klinikum Hochsauerland, Dept Hematol Oncol Palliat Care & Stem Cell Trans, Meschede, Germany

[28] Klinikum Darmstadt, Dept Internal Med 2, Darmstadt, Germany

[29] Klinikum Herford, Dept Internal Med 1, Herford, Germany

[30] Univ Med Ctr Freiburg, Dept Med 2, Div Infect Dis & Travel Med, Freiburg, Germany

[31] Heidelberg Univ Hosp, Natl Ctr Tumor Dis, Dept Med Oncol, Heidelberg, Germany

[32] German Canc Res Ctr, Dept Translat Immunotherapy D24O, Heidelberg, Germany

[33] Helmholtz Inst Translat Oncol, Mainz, Germany

[34] Heidelberg Univ Hosp, Dept Infect Dis, Virol, Heidelberg, Germany

[35] Heidelberg Univ Hosp, Dept Infect Dis, Mol Virol, Heidelberg, Germany

[36] Natl Ctr Tumor Dis, Heidelberg, Germany

来源：

NATURE CANCER | 2023年 / 4卷 / 01期

关键词：

D O I：

10.1038/s43018-022-00503-w

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (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 randomized, open-label, multicenter trial () in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.

引用

页码：96 / +

页数：20

共 37 条

[1] COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study
Avouac, Jerome
Drumez, Elodie
Hachulla, Eric
Seror, Raphaele
Georgin-Lavialle, Sophie
El Mahou, Soumaya
Pertuiset, Edouard
Thao Pham
Marotte, Hubert
Servettaz, Amelie
Domont, Fanny
Chazerain, Pascal
Devaux, Mathilde
Claudepierre, Pascal
Langlois, Vincent
Mekinian, Arsene
Maria, Alexandre Thibault Jacques
Banneville, Beatrice
Fautrel, Bruno
Pouchot, Jacques
Thomas, Thierry
Flipo, Rene-Marc
Richez, Christophe
[J]. LANCET RHEUMATOLOGY, 2021, 3 (06) : E419 - E426
[2] COVID-19 and Solid Organ Transplantation: A Review Article
Azzi, Yorg
Bartash, Rachel
Scalea, Joseph
Loarte-Campos, Pablo
Akalin, Enver
[J]. TRANSPLANTATION, 2021, 105 (01) : 37 - 55
[3] Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial)
Bajpai, Meenu
Maheshwari, Ashish
Dogra, Vikas
Kumar, Suresh
Gupta, Ekta
Kale, Pratibha
Saluja, Vandana
Thomas, Sherin S.
Trehanpati, Nirupama
Bihari, Chhagan
Agarwal, Reshu
Bharti, Praveen
Shankar, Prabha
Hussain, Javid
Chhabra, Karan
Gupta, Amita
Narayanan, Ashad
Agarwal, Sarika
Jain, Shruti
Bhardwaj, Ankit
Kumar, Guresh
Yadav, Birendra Kumar
Sarin, Shiv Kumar
[J]. BMJ OPEN, 2022, 12 (04):
[4] Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial
Begin, Philippe
Callum, Jeannie
Jamula, Erin
Cook, Richard
Heddle, Nancy M.
Tinmouth, Alan
Zeller, Michelle P.
Beaudoin-Bussieres, Guillaume
Amorim, Luiz
Bazin, Renee
Loftsgard, Kent Cadogan
Carl, Richard
Chasse, Michael
Cushing, Melissa M.
Daneman, Nick
Devine, Dana, V
Dumaresq, Jeannot
Fergusson, Dean A.
Gabe, Caroline
Glesby, Marshall J.
Li, Na
Liu, Yang
McGeer, Allison
Robitaille, Nancy
Sachais, Bruce S.
Scales, Damon C.
Schwartz, Lisa
Shehata, Nadine
Turgeon, Alexis F.
Wood, Heidi
Zarychanski, Ryan
Finzi, Andres
Arnold, Donald M.
[J]. NATURE MEDICINE, 2021, 27 (11) : 2012 - +
[5] Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients
Benning, Louise
Morath, Christian
Bartenschlager, Marie
Kim, Heeyoung
Reineke, Marvin
Beimler, Jorg
Buylaert, Mirabel
Nusshag, Christian
Kaelble, Florian
Reichel, Paula
Toellner, Maximilian
Schaier, Matthias
Klein, Katrin
Benes, Vladimir
Rausch, Tobias
Rieger, Susanne
Stich, Maximilian
Toenshoff, Burkhard
Weidner, Niklas
Schnitzler, Paul
Zeier, Martin
Susal, Caner
Tran, Thuong Hien
Bartenschlager, Ralf
Speer, Claudius
[J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2022, 22 (07) : 1873 - 1883
[6] Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients With COVID-19 (April 2020)
Bhimraj, Adarsh
Morgan, Rebecca L.
Shumaker, Amy Hirsch
Lavergne, Valery
Baden, Lindsey
Cheng, Vincent Chi-Chung
Edwards, Kathryn M.
Gandhi, Rajesh
Muller, William J.
O'Horo, John C.
Shoham, Shmuel
Murad, M. Hassan
Mustafa, Reem A.
Sultan, Shahnaz
Falck-Ytter, Yngve
[J]. CLINICAL INFECTIOUS DISEASES, 2020, 78 (07) : e83 - e102
[7] Bilich T, 2021, CANCER DISCOV, V11, P1982, DOI 10.1158/2159-8290.CD-21-0191
[8] Cao B, 2020, NEW ENGL J MED, V382, P1787, DOI [10.1056/NEJMoa2001282, 10.1056/NEJMc2008043]
[9] Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Cavalcanti, A. B.
Zampieri, F. G.
Rosa, R. G.
Azevedo, L. C. P.
Veiga, V. C.
Avezum, A.
Damiani, L. P.
Marcadenti, A.
Kawano-Dourado, L.
Lisboa, T.
Junqueira, D. L. M.
de Barros e Silva, P. G. M.
Tramujas, L.
Abreu-Silva, E. O.
Laranjeira, L. N.
Soares, A. T.
Echenique, L. S.
Pereira, A. J.
Freitas, F. G. R.
Gebara, O. C. E.
Dantas, V. C. S.
Furtado, R. H. M.
Milan, E. P.
Golin, N. A.
Cardoso, F. F.
Maia, I. S.
Hoffmann Filho, C. R.
Kormann, A. P. M.
Amazonas, R. B.
Bocchi de Oliveira, M. F.
Serpa-Neto, A.
Falavigna, M.
Lopes, R. D.
Machado, F. R.
Berwanger, O.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (21) : 2041 - 2052
[10] Corti D, 2021, CELL, V184, P3086, DOI [10.1016/j.cell.2021.05.005, 10.1016/j.cell.2021.07.027]

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