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, Vol. 42, No. 6, 08.2022, p. 1111-1129.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -