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

被引：39

作者：

Gaitzsch, Erik ^{[1
]}

Passerini, Verena ^{[1
]}

Khatamzas, Elham ^{[1
]}

Strobl, Carolin D. ^{[1
]}

Muenchhoff, Maximilian ^{[2
,3
,4
,5
]}

Scherer, Clemens ^{[5
,6
]}

Osterman, Andreas ^{[2
,3
,4
]}

Heide, Michael ^{[1
]}

Reischer, Anna ^{[1
,7
]}

Subklewe, Marion ^{[1
,7
,8
,9
]}

Leutbecher, Alexandra ^{[1
]}

Tast, Benjamin ^{[1
]}

Ruhle, Adrian ^{[2
,3
]}

Weiglein, Tobias ^{[1
]}

Stecher, Stephanie-Susanne ^{[10
]}

Stemmler, Hans J. ^{[1
]}

Dreyling, Martin ^{[1
]}

Girl, Philipp ^{[11
]}

Georgi, Enrico ^{[11
]}

Woelfel, Roman ^{[11
]}

Mateyka, Laura ^{[12
]}

D'Ippolito, Elvira ^{[12
]}

Schober, Kilian ^{[12
]}

Busch, Dirk H. ^{[12
]}

Kager, Juliane ^{[13
]}

Spinner, Christoph D. ^{[14
]}

Treiber, Matthias ^{[14
]}

Rasch, Sebastian ^{[13
]}

Lahmer, Tobias ^{[13
]}

Iakoubov, Roman ^{[13
]}

Schneider, Jochen ^{[13
]}

Protzer, Ulrike ^{[4
,15
]}

Winter, Christof ^{[8
,9
,16
]}

Ruland, Juergen ^{[16
]}

Quante, Michael ^{[12
,13
,17
]}

Keppler, Oliver T. ^{[2
,3
,4
,5
]}

von Bergwelt-Baildon, Michael ^{[1
,5
,8
,9
]}

Hellmuth, Johannes ^{[1
,5
,8
,9
]}

Weigert, Oliver ^{[1
,8
,9
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Dept Med 3, Univ Hosp, Munich, Germany

[2] LMU Munchen, Natl Reference Ctr Retroviruses, Max von Pettenkofer Inst, Munich, Germany

[3] LMU Munchen, Natl Reference Ctr Retroviruses, Gene Ctr, Munich, Germany

[4] German Ctr Infect Res DZIF, Partner Site Munich, Munich, Germany

[5] Ludwig Maximilians Univ Munchen, Univ Hosp, COVID 19 Registry LMU Munich CORKUM, Munich, Germany

[6] Ludwig Maximilians Univ Munchen, Dept Med 1, Univ Hosp, Munich, Germany

[7] Ludwig Maximilians Univ Munchen, Lab Translat Canc Immunol, Gene Ctr, Munich, Germany

[8] German Canc Consortium DKTK, Munich, Germany

[9] German Canc Res Ctr, Heidelberg, Germany

[10] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 2, Munich, Germany

[11] Bundeswehr Inst Microbiol, Munich, Germany

[12] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, Munich, Germany

[13] Tech Univ Munich, Univ Hosp Rechts Isar, Sch Med, Dept Internal Med 2, Munich, Germany

[14] Tech Univ Munich, Univ Hosp Rechts Isar, Sch Med, Munich, Germany

[15] Tech Univ Munich, Inst Virol, Helmholtz Zentrum Munchen, Munich, Germany

[16] Tech Univ Munich, Sch Med, Inst Clin Chem & Pathobiochem, Munich, Germany

[17] Univ Freiburg, Freiburg Univ Med Ctr, Fac Med,Dept Med 2, Gastroenterol Hepatol Endocrinol & Infect Dis, Freiburg, Germany

来源：

HEMASPHERE | 2021年 / 5卷 / 07期

关键词：

RITUXIMAB; GUIDELINES; THERAPY; PHASE-3; CYCLES;

D O I：

10.1097/HS9.0000000000000603

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：10

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