Journal
JOURNAL OF CLINICAL IMMUNOLOGY
Volume 42, Issue 7, Pages 1360-1370Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-022-01308-3
Keywords
COVID-19; Antibodies to type I IFNs; IFN-alpha 2; IFN-omega; Neutralization assay; IFN-alpha 2 concentration
Categories
Funding
- JSPS KAKENHI [JP19H03620, JP19K07940, JP19K08908, JP21K19440, JP19HC1001]
- Research Program on Emerging and Re-emerging Infectious Diseases from AMED [JP20fk0108531, JP20fk0108453, JP20fk0108104j0002]
- Osaka City University Strategic Research Grant [OCU-SRG2021_YR09]
- Howard Hughes Medical Institute
- Rockefeller University
- St. Giles Foundation
- National Institutes of Health (NIH) [R01AI088364, R01AI163029]
- National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program [UL1 TR001866]
- Emergent Ventures
- Mercatus Center at George Mason University
- Fisher Center for Alzheimer's Research Foundation
- Meyer Foundation
- JPB Foundation
- French National Research Agency (ANR) under the Investments for the Future program [ANR-10-IAHU-01]
- French Foundation for Medical Research (FRM) [EQU201903007798]
- ANR GENVIR project [ANR-20-CE93-003]
- ANR AABIFNCOV project [ANR20-CO11-0001]
- ANR GenMISC project [ANR-21-COVR-0039]
- European Union [824110]
- Square Foundation
- Fondation du Souffle
- SCOR Corporate Foundation for Science
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- University of Paris
- French Foundation for Medical Research [EA20170638020]
- MD-PhD program of the Imagine Institute
- Fondation Bettencourt-Schueller
- Grandir-Fonds de solidarite pour l'enfance
- French Ministry of Higher Education
- REACTing-INSERM
- Agence Nationale de la Recherche (ANR) [ANR-21-COVR-0039] Funding Source: Agence Nationale de la Recherche (ANR)
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The study revealed that patients with pre-existing autoantibodies to type I interferons have a higher risk of life-threatening COVID-19 pneumonia in the Japanese population.
Purpose: Autoantibodies (aAbs) to type I interferons (IFNs) have been found in less than 1% of individuals under the age of 60 in the general population, with the prevalence increasing among those over 65. Neutralizing autoantibodies (naAbs) to type I IFNs have been found in at least 15% of patients with life-threatening COVID-19 pneumonia in several cohorts of primarily European descent. We aimed to evaluate the prevalence of aAbs and naAbs to IFN-alpha 2 or IFN-omega in Japanese patients who suffered from COVID-19 as well as in the general population. Methods: Patients who suffered from COVID-19 (n = 622, aged 0-104) and an uninfected healthy control population (n = 3,456, aged 20-91) were enrolled in this study. The severities of the COVID-19 patients were as follows: critical (n = 170), severe (n = 235), moderate (n = 112), and mild (n = 105). ELISA and ISRE reporter assays were used to detect aAbs and naAbs to IFN-alpha 2 and IFN-omega using E. coli-produced IFNs. Results: In an uninfected general Japanese population aged 20-91, aAbs to IFNs were detected in 0.087% of individuals. By contrast, naAbs to type I IFNs (IFN-alpha 2 and/or IFN-omega, 100 pg/mL) were detected in 10.6% of patients with critical infections, 2.6% of patients with severe infections, and 1% of patients with mild infections. The presence of naAbs to IFNs was significantly associated with critical disease (P = 0.0012), age over 50 (P = 0.0002), and male sex (P = 0.137). A significant but not strong correlation between aAbs and naAbs to IFN-alpha 2 existed (r = - 0.307, p value < 0.0001) reinforced the importance of measuring naAbs in COVID-19 patients, including those of Japanese ancestry. Conclusion: In this study, we revealed that patients with pre-existing naAbs have a much higher risk of life-threatening COVID-19 pneumonia in Japanese population.
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