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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.
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.
  • Frasca F; Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Scordio M; Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Santinelli L; Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Gabriele L; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Gandini O; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Criniti A; Department of Experimental Medicine, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
  • Pierangeli A; Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Angeloni A; Department of Experimental Medicine, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
  • Mastroianni CM; Department of Public Health and Infectious Diseases, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
  • d'Ettorre G; Department of Public Health and Infectious Diseases, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
  • Viscidi RP; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Antonelli G; Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Scagnolari C; Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Eur J Immunol ; 52(7): 1120-1128, 2022 07.
Article in English | MEDLINE | ID: covidwho-1929799
ABSTRACT
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/-ß were screened in COVID-19 patients' serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-ß/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-ß/-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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 Type of study: Diagnostic study / Prognostic study / Randomized controlled trials Limits: Humans / Male Language: English Journal: Eur J Immunol Year: 2022 Document Type: Article Affiliation country: Eji.202249824

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 Type of study: Diagnostic study / Prognostic study / Randomized controlled trials Limits: Humans / Male Language: English Journal: Eur J Immunol Year: 2022 Document Type: Article Affiliation country: Eji.202249824