TY - JOUR
T1 - Anti-IFN-α/-ω neutralizing antibodies from COVID-19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
AU - Frasca, Federica
AU - Scordio, Mirko
AU - Santinelli, Letizia
AU - Gabriele, Lucia
AU - Gandini, Orietta
AU - Criniti, Anna
AU - Pierangeli, Alessandra
AU - Angeloni, Antonio
AU - Mastroianni, Claudio M.
AU - d'Ettorre, Gabriella
AU - Viscidi, Raphael P.
AU - Antonelli, Guido
AU - Scagnolari, Carolina
N1 - Publisher Copyright:
© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
PY - 2022/7
Y1 - 2022/7
N2 - A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-β were screened in COVID-19 patients’ serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-β/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-β/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.
AB - A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-β were screened in COVID-19 patients’ serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-β/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-β/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.
KW - COVID-19
KW - ISG
KW - Interferon
KW - autoantibodies, SARS-CoV-2
KW - binding antibodies
KW - neutralizing antibodies
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U2 - 10.1002/eji.202249824
DO - 10.1002/eji.202249824
M3 - Article
C2 - 35419822
AN - SCOPUS:85128826578
SN - 0014-2980
VL - 52
SP - 1120
EP - 1128
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -