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Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity

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/‐...

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Autores principales: Frasca, Federica, Scordio, Mirko, Santinelli, Letizia, Gabriele, Lucia, Gandini, Orietta, Criniti, Anna, Pierangeli, Alessandra, Angeloni, Antonio, Mastroianni, Claudio M., d'Ettorre, Gabriella, Viscidi, Raphael P., Antonelli, Guido, Scagnolari, Carolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087404/
https://www.ncbi.nlm.nih.gov/pubmed/35419822
http://dx.doi.org/10.1002/eji.202249824
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author Frasca, Federica
Scordio, Mirko
Santinelli, Letizia
Gabriele, Lucia
Gandini, Orietta
Criniti, Anna
Pierangeli, Alessandra
Angeloni, Antonio
Mastroianni, Claudio M.
d'Ettorre, Gabriella
Viscidi, Raphael P.
Antonelli, Guido
Scagnolari, Carolina
author_facet Frasca, Federica
Scordio, Mirko
Santinelli, Letizia
Gabriele, Lucia
Gandini, Orietta
Criniti, Anna
Pierangeli, Alessandra
Angeloni, Antonio
Mastroianni, Claudio M.
d'Ettorre, Gabriella
Viscidi, Raphael P.
Antonelli, Guido
Scagnolari, Carolina
author_sort Frasca, Federica
collection PubMed
description 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.
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spelling pubmed-90874042022-05-10 Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity Frasca, Federica Scordio, Mirko Santinelli, Letizia Gabriele, Lucia Gandini, Orietta Criniti, Anna Pierangeli, Alessandra Angeloni, Antonio Mastroianni, Claudio M. d'Ettorre, Gabriella Viscidi, Raphael P. Antonelli, Guido Scagnolari, Carolina Eur J Immunol Immunity to infection 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. John Wiley and Sons Inc. 2022-04-28 2022-07 /pmc/articles/PMC9087404/ /pubmed/35419822 http://dx.doi.org/10.1002/eji.202249824 Text en © 2022 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Immunity to infection
Frasca, Federica
Scordio, Mirko
Santinelli, Letizia
Gabriele, Lucia
Gandini, Orietta
Criniti, Anna
Pierangeli, Alessandra
Angeloni, Antonio
Mastroianni, Claudio M.
d'Ettorre, Gabriella
Viscidi, Raphael P.
Antonelli, Guido
Scagnolari, Carolina
Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
title Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
title_full Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
title_fullStr Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
title_full_unstemmed Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
title_short Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
title_sort anti‐ifn‐α/‐ω neutralizing antibodies from covid‐19 patients correlate with downregulation of ifn response and laboratory biomarkers of disease severity
topic Immunity to infection
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087404/
https://www.ncbi.nlm.nih.gov/pubmed/35419822
http://dx.doi.org/10.1002/eji.202249824
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