Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies

被引:19
作者
Magyari, Ferenc [1 ,2 ]
Pinczes, Laszlo Imre [1 ,2 ]
Payer, Edit [1 ,2 ]
Farkas, Katalin [1 ,2 ]
Ujfalusi, Szilvia [3 ]
Dioszegi, Agnes [3 ]
Sik, Mate [4 ]
Simon, Zsofia [1 ]
Nagy, Gergely [5 ]
Hevessy, Zsuzsanna [6 ]
Nagy, Bela [6 ]
Illes, Arpad [1 ,2 ]
机构
[1] Univ Debrecen, Fac Med, Dept Internal Med, Div Hematol, Debrecen, Hungary
[2] Univ Debrecen, Doctoral Sch Clin Med, Debrecen, Hungary
[3] Univ Debrecen, Fac Med, Dept Internal Med, Div Endocrinol, Debrecen, Hungary
[4] Univ Debrecen, Fac Med, Dept Radiol, Debrecen, Hungary
[5] Univ Debrecen, Fac Med, Dept Emergency Med, Debrecen, Hungary
[6] Univ Debrecen, Fac Med, Dept Lab Med, Debrecen, Hungary
关键词
COVID-19; SARS-CoV-2; Convalescent plasma treatment; Remdesivir; Hematological malignancies; Immunodeficiency;
D O I
10.1007/s00277-022-04924-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Patients with hematological malignancies (HMs) are at a higher risk of developing severe form and protracted course of COVID-19 disease. We investigated whether the combination of viral replication inhibition with remdesivir and administration of anti-SARS-CoV-2 immunoglobulins with convalescent plasma (CP) therapy might be sufficient to treat B-cell-depleted patients with COVID-19. We enrolled 20 consecutive patients with various HMs with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. All patients demonstrated undetectable baseline anti-SARS-CoV-2 immunoglobulin levels before CP. Each patient received at least a complete course of remdesivir and at least one unit of CP. Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of B-cell lymphopenia (p = 0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p = 0.017), length of hospital stay (p = 0.007), and PCR positivity (p = 0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p < 0.001) and hospital stay (p < 0.0001). In those cases where there were at least 10 days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p = 0.006). In conclusion, the combination of inhibition of viral replication with passive immunization was proved to be efficient and safe. Our results suggest the clear benefit of early, combined administration of remdesivir and CP to avoid protracted COVID-19 disease among patients with HMs and B-cell lymphopenia.
引用
收藏
页码:2337 / 2345
页数:9
相关论文
共 33 条
  • [21] Sustained Response After Remdesivir and Convalescent Plasma Therapy in a B-Cell-Depleted Patient With Protracted Coronavirus Disease 2019 (COVID-19)
    Malsy, Jakob
    Veletzky, Luzia
    Heide, Janna
    Hennigs, Annette
    Gil-Ibanez, Ines
    Stein, Alexander
    Lutgehetmann, Marc
    Rosien, Ulrich
    Jasper, Dorothea
    Peine, Sven
    Hiller, Jens
    Haag, Friedrich
    Schmiedel, Stefan
    Huber, Samuel
    Jordan, Sabine
    Addo, Marylyn M.
    zur Wiesch, Julian Schulze
    [J]. CLINICAL INFECTIOUS DISEASES, 2021, 73 (11) : E4020 - E4024
  • [22] A minimal common outcome measure set for COVID-19 clinical research
    Marshall, J. C.
    Murthy, S.
    Diaz, J.
    Cheng, A.
    Denholm, J.
    Hodgson, C.
    Tong, S.
    Webb, S.
    Bozza, F.
    Adhikari, N.
    Foster, N.
    Fowler, R.
    Turgeon, A.
    Feng, X.
    Qiu, R.
    Shi, L.
    Zhang, J.
    Kojan, R.
    Malvey, D.
    Bauer, M.
    Brunkhorst, F.
    Glueck, T.
    Wolf, T.
    Gomersall, C.
    Kumar, B.
    Clarke, M.
    Laffey, J.
    Martin-Loeches, I
    Piva, S.
    Shimizu, N.
    de Jong, M.
    Derde, L.
    Netea, M.
    van de Veerdonk, F.
    McArthur, C.
    McBride, S.
    McGuinness, S.
    Morpeth, S.
    Salisu-Kabara, H.
    Sinclair, J.
    Arabi, Y. M.
    Kim, Y.
    Oh, M-D
    Baillie, K.
    Dunning, J.
    Fletcher, T.
    Gobat, N.
    Gordon, A.
    Horby, P.
    McAuley, D.
    [J]. LANCET INFECTIOUS DISEASES, 2020, 20 (08) : E192 - E197
  • [23] Nussenblatt V, 2022, J INFECT DIS, V225, P1118, DOI [10.1101/2021.10.02.21264267, 10.1093/infdis/jiab622]
  • [24] COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)
    Pagano, Livio
    Salmanton-Garcia, Jon
    Marchesi, Francesco
    Busca, Alessandro
    Corradini, Paolo
    Hoenigl, Martin
    Klimko, Nikolai
    Koehler, Philipp
    Pagliuca, Antonio
    Passamonti, Francesco
    Verga, Luisa
    Visek, Benjamin
    Ilhan, Osman
    Nadali, Gianpaolo
    Weinbergerova, Barbora
    Cordoba-Mascunano, Raul
    Marchetti, Monia
    Collins, Graham P.
    Farina, Francesca
    Cattaneo, Chiara
    Cabirta, Alba
    Gomes-Silva, Maria
    Itri, Federico
    van Doesum, Jaap
    Ledoux, Marie-Pierre
    Cernan, Martin
    Jaksic, Ozren
    Duarte, Rafael F.
    Magliano, Gabriele
    Omrani, Ali S.
    Fracchiolla, Nicola S.
    Kulasekararaj, Austin
    Valkovic, Toni
    Poulsen, Christian Bjorn
    Machado, Marina
    Glenthoj, Andreas
    Stoma, Igor
    Racil, Zdenek
    Piukovics, Klara
    Navratil, Milan
    Emarah, Ziad
    Sili, Uluhan
    Maertens, Johan
    Blennow, Ola
    Bergantim, Rui
    Garcia-Vidal, Carolina
    Prezioso, Lucia
    Guidetti, Anna
    del Principe, Maria Ilaria
    Popova, Marina
    [J]. JOURNAL OF HEMATOLOGY & ONCOLOGY, 2021, 14 (01)
  • [25] Rodionov RN, 2021, LANCET MICROBE, V2, pE138, DOI 10.1016/S2666-5247(21)00030-6
  • [26] Consequences of B-cell-depleting therapy: hypogammaglobulinemia and impaired B-cell reconstitution
    Sacco, Keith A.
    Abraham, Roshini S.
    [J]. IMMUNOTHERAPY, 2018, 10 (08) : 713 - 728
  • [27] Convalescent plasma and remdesivir for protracted COVID-19 in a patient with chronic lymphocytic leukaemia: a case report of late relapse after rapid initial response
    Schenker, Carla
    Hirzel, Cedric
    Walti, Laura N.
    Zeerleder, Sacha S.
    Andres, Martin
    Ramette, Alban
    Barbani, Maria T.
    Suter-Riniker, Franziska
    Holbro, Andreas
    Tritschler, Tobias
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2022, 196 (03) : E27 - E29
  • [28] A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia
    Simonovich, V. A.
    Pratx, L. D. Burgos
    Sabana, P.
    Beruto, M., V
    Vallone, M. G.
    Vazquez, C.
    Savoy, N.
    Giunta, D. H.
    Perez, L. G.
    Sanchez, M. L.
    Gamarnik, A., V
    Ojeda, D. S.
    Santoro, D. M.
    Camino, P. J.
    Antelo, S.
    Rainero, K.
    Vidiella, G. P.
    Miyazaki, E. A.
    Cornistein, W.
    Trabadelo, O. A.
    Ross, F. M.
    Spotti, M.
    Funtowicz, G.
    Scordo, W. E.
    Losso, M. H.
    Ferniot, I
    Pardo, P. E.
    Rodriguez, E.
    Rucci, P.
    Pasquali, J.
    Fuentes, N. A.
    Esperatti, M.
    Speroni, G. A.
    Nannini, E. C.
    Matteaccio, A.
    Michelangelo, H. G.
    Follmann, D.
    Lane, H. C.
    Belloso, W. H.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (07) : 619 - 629
  • [29] Persisting SARS-CoV-2 viraemia after rituximab therapy: two cases with fatal outcome and a review of the literature
    Tepasse, Phil-Robin
    Hafezi, Wali
    Lutz, Mathias
    Kuehn, Joachim
    Wilms, Christian
    Wiewrodt, Rainer
    Sackarnd, Jan
    Keller, Martin
    Schmidt, Hartmut H.
    Vollenberg, Richard
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2020, 190 (02) : 185 - 188
  • [30] Association of Convalescent Plasma Therapy With Survival in Patients With Hematologic Cancers and COVID-19
    Thompson, Michael A.
    Henderson, Jeffrey P.
    Shah, Pankil K.
    Rubinstein, Samuel M.
    Joyner, Michael J.
    Choueiri, Toni K.
    Flora, Daniel B.
    Griffiths, Elizabeth A.
    Gulati, Anthony P.
    Hwang, Clara
    Koshkin, Vadim S.
    Papadopoulos, Esperanza B.
    Robilotti, Elizabeth, V
    Su, Christopher T.
    Wulff-Burchfield, Elizabeth M.
    Xie, Zhuoer
    Yu, Peter Paul
    Mishra, Sanjay
    Senefeld, Jonathon W.
    Shah, Dimpy P.
    Warner, Jeremy L.
    [J]. JAMA ONCOLOGY, 2021, 7 (08) : 1167 - 1175