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Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1ß associate with COVID-19 fatal outcome: A cross-sectional analysis.
Ruiz, Maria Julia; Siracusano, Gabriel; Cottignies-Calamarte, Andréa; Tudor, Daniela; Real, Fernando; Zhu, Aiwei; Pastori, Claudia; Capron, Claude; Rosenberg, Arielle R; Temperton, Nigel; Cantoni, Diego; Liao, Hanqing; Ternette, Nicola; Moine, Pierre; Godement, Mathieu; Geri, Guillaume; Chiche, Jean-Daniel; Annane, Djillali; Cramer Bordé, Elisabeth; Lopalco, Lucia; Bomsel, Morgane.
  • Ruiz MJ; Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France.
  • Siracusano G; INSERM U1016, Paris, France.
  • Cottignies-Calamarte A; CNRS UMR8104, Paris, France.
  • Tudor D; Immunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, Italy.
  • Real F; Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France.
  • Zhu A; INSERM U1016, Paris, France.
  • Pastori C; CNRS UMR8104, Paris, France.
  • Capron C; Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France.
  • Rosenberg AR; INSERM U1016, Paris, France.
  • Temperton N; CNRS UMR8104, Paris, France.
  • Cantoni D; Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France.
  • Liao H; INSERM U1016, Paris, France.
  • Ternette N; CNRS UMR8104, Paris, France.
  • Moine P; Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France.
  • Godement M; INSERM U1016, Paris, France.
  • Geri G; CNRS UMR8104, Paris, France.
  • Chiche JD; Immunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, Italy.
  • Annane D; AP-HP, Hôpital Ambroise Paré, Service d'Hématologie, Boulogne-Billancourt, France.
  • Cramer Bordé E; Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France.
  • Lopalco L; INSERM U1016, Paris, France.
  • Bomsel M; CNRS UMR8104, Paris, France.
Front Immunol ; 13: 842468, 2022.
Article in English | MEDLINE | ID: covidwho-2080127
ABSTRACT
The role of the mucosal pulmonary antibody response in coronavirus disease 2019 (COVID-19) outcome remains unclear. Here, we found that in bronchoalveolar lavage (BAL) samples from 48 patients with severe COVID-19-infected with the ancestral Wuhan virus, mucosal IgG and IgA specific for S1, receptor-binding domain (RBD), S2, and nucleocapsid protein (NP) emerged in BAL containing viruses early in infection and persist after virus elimination, with more IgA than IgG for all antigens tested. Furthermore, spike-IgA and spike-IgG immune complexes were detected in BAL, especially when the lung virus has been cleared. BAL IgG and IgA recognized the four main RBD variants. BAL neutralizing titers were higher early in COVID-19 when virus replicates in the lung than later in infection after viral clearance. Patients with fatal COVID-19, in contrast to survivors, developed higher levels of mucosal spike-specific IgA than IgG but lost neutralizing activities over time and had reduced IL-1ß in the lung. Altogether, mucosal spike and NP-specific IgG and S1-specific IgA persisting after lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance and low pulmonary IL-1ß correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization. Highlights Mucosal pulmonary antibody response in COVID-19 outcome remains unclear. We show that in severe COVID-19 patients, mucosal pulmonary non-neutralizing SARS-CoV-2 IgA persit after viral clearance in the lung. Furthermore, low lung IL-1ß correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-1beta / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.842468

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-1beta / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.842468