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

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Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies. / Akbil, Bengisu; Meyer, Tim; Stubbemann, Paula; Thibeault, Charlotte; Staudacher, Olga; Niemeyer, Daniela; Jansen, Jenny; Mühlemann, Barbara; Doehn, Jan; Tabeling, Christoph; Nusshag, Christian; Hirzel, Cédric; Sanchez, David Sökler; Nieters, Alexandra; Lother, Achim; Duerschmied, Daniel; Schallner, Nils; Lieberum, Jan Nikolaus; August, Dietrich; Rieg, Siegbert; Falcone, Valeria; Hengel, Hartmut; Kölsch, Uwe; Unterwalder, Nadine; Hübner, Ralf-Harto; Jones, Terry C; Suttorp, Norbert; Drosten, Christian; Warnatz, Klaus; Spinetti, Thibaud; Schefold, Joerg C; Dörner, Thomas; Sander, Leif Erik; Corman, Victor M; Merle, Uta; Kurth, Florian; von Bernuth, Horst; Meisel, Christian; Goffinet, Christine; Pa-COVID Study Group.

in: J CLIN IMMUNOL, Jahrgang 42, Nr. 6, 08.2022, S. 1111-1129.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Akbil, B, Meyer, T, Stubbemann, P, Thibeault, C, Staudacher, O, Niemeyer, D, Jansen, J, Mühlemann, B, Doehn, J, Tabeling, C, Nusshag, C, Hirzel, C, Sanchez, DS, Nieters, A, Lother, A, Duerschmied, D, Schallner, N, Lieberum, JN, August, D, Rieg, S, Falcone, V, Hengel, H, Kölsch, U, Unterwalder, N, Hübner, R-H, Jones, TC, Suttorp, N, Drosten, C, Warnatz, K, Spinetti, T, Schefold, JC, Dörner, T, Sander, LE, Corman, VM, Merle, U, Kurth, F, von Bernuth, H, Meisel, C, Goffinet, C & Pa-COVID Study Group 2022, 'Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies', J CLIN IMMUNOL, Jg. 42, Nr. 6, S. 1111-1129. https://doi.org/10.1007/s10875-022-01252-2

APA

Akbil, B., Meyer, T., Stubbemann, P., Thibeault, C., Staudacher, O., Niemeyer, D., Jansen, J., Mühlemann, B., Doehn, J., Tabeling, C., Nusshag, C., Hirzel, C., Sanchez, D. S., Nieters, A., Lother, A., Duerschmied, D., Schallner, N., Lieberum, J. N., August, D., ... Pa-COVID Study Group (2022). Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies. J CLIN IMMUNOL, 42(6), 1111-1129. https://doi.org/10.1007/s10875-022-01252-2

Vancouver

Akbil B, Meyer T, Stubbemann P, Thibeault C, Staudacher O, Niemeyer D et al. Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies. J CLIN IMMUNOL. 2022 Aug;42(6):1111-1129. https://doi.org/10.1007/s10875-022-01252-2

Bibtex

@article{9e7f813dedc74010a18b3fee5762a7b5,
title = "Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies",
abstract = "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-α and IFN-ω 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-α-AABs and 4.6%, 11/237 for IFN-ω-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.",
keywords = "Antibodies, Neutralizing, Autoantibodies, COVID-19/diagnosis, Critical Illness, Female, Humans, Interferon Type I, Interferon-alpha/therapeutic use, Male, Oxygen, SARS-CoV-2",
author = "Bengisu Akbil and Tim Meyer and Paula Stubbemann and Charlotte Thibeault and Olga Staudacher and Daniela Niemeyer and Jenny Jansen and Barbara M{\"u}hlemann and Jan Doehn and Christoph Tabeling and Christian Nusshag and C{\'e}dric Hirzel and Sanchez, {David S{\"o}kler} and Alexandra Nieters and Achim Lother and Daniel Duerschmied and Nils Schallner and Lieberum, {Jan Nikolaus} and Dietrich August and Siegbert Rieg and Valeria Falcone and Hartmut Hengel and Uwe K{\"o}lsch and Nadine Unterwalder and Ralf-Harto H{\"u}bner and Jones, {Terry C} and Norbert Suttorp and Christian Drosten and Klaus Warnatz and Thibaud Spinetti and Schefold, {Joerg C} and Thomas D{\"o}rner and Sander, {Leif Erik} and Corman, {Victor M} and Uta Merle and Florian Kurth and {von Bernuth}, Horst and Christian Meisel and Christine Goffinet and {Pa-COVID Study Group}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = aug,
doi = "10.1007/s10875-022-01252-2",
language = "English",
volume = "42",
pages = "1111--1129",
journal = "J CLIN IMMUNOL",
issn = "0271-9142",
publisher = "Springer New York",
number = "6",

}

RIS

TY - JOUR

T1 - Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

AU - Akbil, Bengisu

AU - Meyer, Tim

AU - Stubbemann, Paula

AU - Thibeault, Charlotte

AU - Staudacher, Olga

AU - Niemeyer, Daniela

AU - Jansen, Jenny

AU - Mühlemann, Barbara

AU - Doehn, Jan

AU - Tabeling, Christoph

AU - Nusshag, Christian

AU - Hirzel, Cédric

AU - Sanchez, David Sökler

AU - Nieters, Alexandra

AU - Lother, Achim

AU - Duerschmied, Daniel

AU - Schallner, Nils

AU - Lieberum, Jan Nikolaus

AU - August, Dietrich

AU - Rieg, Siegbert

AU - Falcone, Valeria

AU - Hengel, Hartmut

AU - Kölsch, Uwe

AU - Unterwalder, Nadine

AU - Hübner, Ralf-Harto

AU - Jones, Terry C

AU - Suttorp, Norbert

AU - Drosten, Christian

AU - Warnatz, Klaus

AU - Spinetti, Thibaud

AU - Schefold, Joerg C

AU - Dörner, Thomas

AU - Sander, Leif Erik

AU - Corman, Victor M

AU - Merle, Uta

AU - Kurth, Florian

AU - von Bernuth, Horst

AU - Meisel, Christian

AU - Goffinet, Christine

AU - Pa-COVID Study Group

N1 - © 2022. The Author(s).

PY - 2022/8

Y1 - 2022/8

N2 - 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-α and IFN-ω 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-α-AABs and 4.6%, 11/237 for IFN-ω-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.

AB - 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-α and IFN-ω 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-α-AABs and 4.6%, 11/237 for IFN-ω-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.

KW - Antibodies, Neutralizing

KW - Autoantibodies

KW - COVID-19/diagnosis

KW - Critical Illness

KW - Female

KW - Humans

KW - Interferon Type I

KW - Interferon-alpha/therapeutic use

KW - Male

KW - Oxygen

KW - SARS-CoV-2

U2 - 10.1007/s10875-022-01252-2

DO - 10.1007/s10875-022-01252-2

M3 - SCORING: Journal article

C2 - 35511314

VL - 42

SP - 1111

EP - 1129

JO - J CLIN IMMUNOL

JF - J CLIN IMMUNOL

SN - 0271-9142

IS - 6

ER -