Frontiers in Immunology (Sep 2022)
Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis
- Maria Julia Ruiz,
- Maria Julia Ruiz,
- Maria Julia Ruiz,
- Gabriel Siracusano,
- Andréa Cottignies-Calamarte,
- Andréa Cottignies-Calamarte,
- Andréa Cottignies-Calamarte,
- Daniela Tudor,
- Daniela Tudor,
- Daniela Tudor,
- Fernando Real,
- Fernando Real,
- Fernando Real,
- Aiwei Zhu,
- Aiwei Zhu,
- Aiwei Zhu,
- Claudia Pastori,
- Claude Capron,
- Arielle R. Rosenberg,
- Arielle R. Rosenberg,
- Arielle R. Rosenberg,
- Arielle R. Rosenberg,
- Nigel Temperton,
- Diego Cantoni,
- Hanqing Liao,
- Nicola Ternette,
- Pierre Moine,
- Mathieu Godement,
- Guillaume Geri,
- Guillaume Geri,
- Jean-Daniel Chiche,
- Djillali Annane,
- Elisabeth Cramer Bordé,
- Lucia Lopalco,
- Morgane Bomsel,
- Morgane Bomsel,
- Morgane Bomsel
Affiliations
- Maria Julia Ruiz
- Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France
- Maria Julia Ruiz
- INSERM U1016, Paris, France
- Maria Julia Ruiz
- CNRS UMR8104, Paris, France
- Gabriel Siracusano
- Immunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, Italy
- Andréa Cottignies-Calamarte
- Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France
- Andréa Cottignies-Calamarte
- INSERM U1016, Paris, France
- Andréa Cottignies-Calamarte
- CNRS UMR8104, Paris, France
- Daniela Tudor
- Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France
- Daniela Tudor
- INSERM U1016, Paris, France
- Daniela Tudor
- CNRS UMR8104, Paris, France
- Fernando Real
- Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France
- Fernando Real
- INSERM U1016, Paris, France
- Fernando Real
- CNRS UMR8104, Paris, France
- Aiwei Zhu
- Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France
- Aiwei Zhu
- INSERM U1016, Paris, France
- Aiwei Zhu
- CNRS UMR8104, Paris, France
- Claudia Pastori
- Immunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, Italy
- Claude Capron
- AP-HP, Hôpital Ambroise Paré, Service d'Hématologie, Boulogne-Billancourt, France
- Arielle R. Rosenberg
- Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France
- Arielle R. Rosenberg
- INSERM U1016, Paris, France
- Arielle R. Rosenberg
- CNRS UMR8104, Paris, France
- Arielle R. Rosenberg
- AP-HP, Hôpital Cochin, Service de Virologie, Paris, France
- Nigel Temperton
- Viral Pseudotype Unit, Medway School of Pharmacy, The Universities of Kent and Greenwich at Medway, Chatham, United Kingdom
- Diego Cantoni
- Viral Pseudotype Unit, Medway School of Pharmacy, The Universities of Kent and Greenwich at Medway, Chatham, United Kingdom
- Hanqing Liao
- Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Nicola Ternette
- Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Pierre Moine
- FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis), RHU RECORDS (Rapid rEcognition of CORticosteroiD resistant or sensitive Sepsis), Department of Intensive Care, Hôpital Raymond Poincaré (APHP), Laboratory of Infection and Inflammation – U1173, School of Medicine Simone Veil, University Versailles Saint Quentin – University Paris Saclay, INSERM, Garches, France
- Mathieu Godement
- FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis), RHU RECORDS (Rapid rEcognition of CORticosteroiD resistant or sensitive Sepsis), Department of Intensive Care, Hôpital Raymond Poincaré (APHP), Laboratory of Infection and Inflammation – U1173, School of Medicine Simone Veil, University Versailles Saint Quentin – University Paris Saclay, INSERM, Garches, France
- Guillaume Geri
- 0AP-HP, Hôpital Ambroise Paré, Service de Réanimation, Boulogne-Billancourt, France
- Guillaume Geri
- 1Université de Versailles-St Quentin en Yvelines, Versailles, France
- Jean-Daniel Chiche
- 2AP-HP, Hôpital Cochin, Service de Réanimation, Paris, France
- Djillali Annane
- FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis), RHU RECORDS (Rapid rEcognition of CORticosteroiD resistant or sensitive Sepsis), Department of Intensive Care, Hôpital Raymond Poincaré (APHP), Laboratory of Infection and Inflammation – U1173, School of Medicine Simone Veil, University Versailles Saint Quentin – University Paris Saclay, INSERM, Garches, France
- Elisabeth Cramer Bordé
- 1Université de Versailles-St Quentin en Yvelines, Versailles, France
- Lucia Lopalco
- Immunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, Italy
- Morgane Bomsel
- Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, France
- Morgane Bomsel
- INSERM U1016, Paris, France
- Morgane Bomsel
- CNRS UMR8104, Paris, France
- DOI
- https://doi.org/10.3389/fimmu.2022.842468
- Journal volume & issue
-
Vol. 13
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-1β 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-1β correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization.HighlightsMucosal 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-1β correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.
Keywords
