Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

被引：27

作者：

Akbil, Bengisu ^{[1
,2
,3
,4
]}

Meyer, Tim ^{[5
]}

Stubbemann, Paula ^{[6
,7
,8
]}

Thibeault, Charlotte ^{[6
,7
,8
]}

Staudacher, Olga ^{[5
,7
,8
,9
,10
]}

Niemeyer, Daniela ^{[1
,2
,3
,11
]}

Jansen, Jenny ^{[1
,2
,3
,4
]}

Muehlemann, Barbara ^{[1
,2
,3
,11
]}

Doehn, Jan ^{[6
,7
,8
]}

Tabeling, Christoph ^{[4
,6
,7
,8
]}

Nusshag, Christian ^{[12
]}

Hirzel, Cedric ^{[13
]}

Sanchez, David Soekler ^{[14
,15
]}

Nieters, Alexandra ^{[16
,17
]}

Lother, Achim ^{[18
]}

Duerschmied, Daniel ^{[18
]}

Schallner, Nils ^{[19
,20
]}

Lieberum, Jan Nikolaus ^{[19
,20
]}

August, Dietrich ^{[21
]}

Rieg, Siegbert ^{[21
]}

Falcone, Valeria ^{[22
]}

Hengel, Hartmut ^{[22
]}

Koelsch, Uwe ^{[5
]}

Unterwalder, Nadine ^{[5
]}

Huebner, Ralf-Harto ^{[4
,6
,7
,8
]}

Jones, Terry C. ^{[1
,2
,3
,11
,23
]}

Suttorp, Norbert ^{[6
,7
,8
]}

Drosten, Christian ^{[1
,2
,3
,11
]}

Warnatz, Klaus ^{[14
,15
]}

Spinetti, Thibaud ^{[24
]}

Schefold, Joerg C. ^{[24
]}

Doerner, Thomas ^{[25
,26
,27
,28
]}

Sander, Leif Erik ^{[6
,7
,8
]}

Corman, Victor M. ^{[1
,2
,3
,11
,29
]}

Merle, Uta ^{[30
]}

Kurth, Florian ^{[6
,7
,8
,31
,32
]}

von Bernuth, Horst ^{[4
,5
,7
,8
,9
,10
,26
,27
,33
,34
]}

Meisel, Christian ^{[5
,26
,27
,35
]}

Goffinet, Christine ^{[1
,2
,3
,4
]}

机构：

[1] Charite Univ Med Berlin, Inst Virol, Charitepl 1, D-10117 Berlin, Germany

[2] Free Univ Berlin, Charitepl 1, D-10117 Berlin, Germany

[3] Humboldt Univ, Charitepl 1, D-10117 Berlin, Germany

[4] Charite Univ Med Berlin, Berlin Inst Hlth, Berlin, Germany

[5] Charite Univ Med Berlin, Dept Immunol, Lab Berlin GmbH, Sylter Str 2, D-13353 Berlin, Germany

[6] Charite Univ Med Berlin, Dept Infect Dis & Resp Med, Augustenburger Pl 1, D-13353 Berlin, Germany

[7] Free Univ Berlin, Augustenburger Pl 1, D-13353 Berlin, Germany

[8] Humboldt Univ, Augustenburger Pl 1, D-13353 Berlin, Germany

[9] Charite Univ Med Berlin, Dept Pediat Resp Med Immunol & Crit Care Med, Augustenburger Pl 1, D-13353 Berlin, Germany

[10] Berlin Inst Hlth, Augustenburger Pl 1, D-13353 Berlin, Germany

[11] DZIF German Ctr Infect Res DZIF, Partner Site Charite, D-10117 Berlin, Germany

[12] Heidelberg Univ Hosp, Dept Nephrol, Heidelberg, Germany

[13] Univ Bern, Bern Univ Hosp, Dept Infect Dis, Inselspital, Bern, Switzerland

[14] Univ Freiburg, Med Ctr, Fac Med, Dept Rheumatol & Clin Immunol, Freiburg, Germany

[15] Univ Freiburg, Med Ctr, Fac Med, Ctr Chron Immunodeficiency CCI, Freiburg, Germany

[16] Univ Freiburg, Univ Med Ctr Freiburg, Ctr Biobanking, FREEZE Biobank, Freiburg, Germany

[17] Univ Freiburg, Fac Med, Ctr Biobanking, FREEZE Biobank, Freiburg, Germany

[18] Univ Freiburg, Fac Med, Heart Ctr, Cardiol & Med Intens Care, Freiburg, Germany

[19] Univ Freiburg, Dept Anesthesiol & Crit Care, Med Ctr, Freiburg, Germany

[20] Univ Freiburg, Fac Med, Freiburg, Germany

[21] Univ Freiburg, Med Ctr, Fac Med, Dept Med 2,Div Infect Dis, D-79106 Freiburg, Germany

[22] Albert Ludwigs Univ Freiburg, Freiburg Univ Med Ctr, Fac Med, Inst Virol, Freiburg, Germany

[23] Univ Cambridge, Ctr Pathogen Evolut, Dept Zool, Downing St, Cambridge CB2 3EJ, England

[24] Univ Bern, Bern Univ Hosp, Dept Intens Care Med, Inselspital, Freiburgstr, CH-3010 Bern, Switzerland

[25] Charite Univ Med Berlin, Dept Med Rheumatol & Clin Immunol, Berlin, Germany

[26] Free Univ Berlin, Berlin, Germany

[27] Humboldt Univ, Berlin, Germany

[28] DRFZ, Berlin, Germany

[29] Lab Berlin GmbH, Berlin, Germany

[30] Heidelberg Univ Hosp, Dept Gastroenterol, Heidelberg, Germany

[31] Univ Med Ctr Hamburg Eppendorf, Bernhard Nocht Inst Trop Med, Dept Trop Med, Hamburg, Germany

[32] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Hamburg, Germany

[33] Charite Univ Med Berlin, Berlin, Germany

[34] Berlin Inst Hlth BIH, Berlin Brandenburg Ctr Regenerat Therapies BCRT, Berlin, Germany

[35] Charite Univ Med Berlin, Inst Med Immunol, Berlin, Germany

来源：

JOURNAL OF CLINICAL IMMUNOLOGY | 2022年 / 42卷 / 06期

关键词：

COVID-19; SARS-CoV-2; Type I interferon; Autoantibodies; ANTIBODY;

D O I：

10.1007/s10875-022-01252-2

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Purpose Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions. Methods We analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome. Results The prevalence of neutralizing AABs to IFN-alpha and IFN-omega in COVID-19 patients from all cohorts was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected (max. WHO score 6-8), predominantly male (83%) patients (7.6%, 18/237 for IFN-alpha-AABs and 4.6%, 11/237 for IFN-omega-AABs in 237 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with lower probability of survival (7.7% versus 80.9% in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE. Conclusion IFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.

引用

页码：1111 / 1129

页数：19

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