Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis
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...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.842468/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Maria Julia Ruiz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:13:49Z |
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| id | doaj.art-da0c0729bf124803ba74929d5054462a |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T05:13:49Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-da0c0729bf124803ba74929d5054462a2022-12-22T02:01:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.842468842468Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysisMaria Julia Ruiz0Maria Julia Ruiz1Maria Julia Ruiz2Gabriel Siracusano3Andréa Cottignies-Calamarte4Andréa Cottignies-Calamarte5Andréa Cottignies-Calamarte6Daniela Tudor7Daniela Tudor8Daniela Tudor9Fernando Real10Fernando Real11Fernando Real12Aiwei Zhu13Aiwei Zhu14Aiwei Zhu15Claudia Pastori16Claude Capron17Arielle R. Rosenberg18Arielle R. Rosenberg19Arielle R. Rosenberg20Arielle R. Rosenberg21Nigel Temperton22Diego Cantoni23Hanqing Liao24Nicola Ternette25Pierre Moine26Mathieu Godement27Guillaume Geri28Guillaume Geri29Jean-Daniel Chiche30Djillali Annane31Elisabeth Cramer Bordé32Lucia Lopalco33Morgane Bomsel34Morgane Bomsel35Morgane Bomsel36Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, FranceINSERM U1016, Paris, FranceCNRS UMR8104, Paris, FranceImmunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, ItalyMucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, FranceINSERM U1016, Paris, FranceCNRS UMR8104, Paris, FranceMucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, FranceINSERM U1016, Paris, FranceCNRS UMR8104, Paris, FranceMucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, FranceINSERM U1016, Paris, FranceCNRS UMR8104, Paris, FranceMucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, FranceINSERM U1016, Paris, FranceCNRS UMR8104, Paris, FranceImmunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, ItalyAP-HP, Hôpital Ambroise Paré, Service d'Hématologie, Boulogne-Billancourt, FranceMucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, FranceINSERM U1016, Paris, FranceCNRS UMR8104, Paris, FranceAP-HP, Hôpital Cochin, Service de Virologie, Paris, FranceViral Pseudotype Unit, Medway School of Pharmacy, The Universities of Kent and Greenwich at Medway, Chatham, United KingdomViral Pseudotype Unit, Medway School of Pharmacy, The Universities of Kent and Greenwich at Medway, Chatham, United KingdomCentre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomCentre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomFHU 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, FranceFHU 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, France0AP-HP, Hôpital Ambroise Paré, Service de Réanimation, Boulogne-Billancourt, France1Université de Versailles-St Quentin en Yvelines, Versailles, France2AP-HP, Hôpital Cochin, Service de Réanimation, Paris, FranceFHU 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, France1Université de Versailles-St Quentin en Yvelines, Versailles, FranceImmunobiology of HIV Unit, San Raffaele Scientific Institute, Milan, ItalyMucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Paris-Descartes University, Paris, FranceINSERM U1016, Paris, FranceCNRS UMR8104, Paris, FranceThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.842468/fullSARS-CoV-2COVID-19mucosal immunityIgAsevere infectioninflammatory cytokine |
| spellingShingle | 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 Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis Frontiers in Immunology SARS-CoV-2 COVID-19 mucosal immunity IgA severe infection inflammatory cytokine |
| title | Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis |
| title_full | Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis |
| title_fullStr | Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis |
| title_full_unstemmed | Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis |
| title_short | Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis |
| title_sort | persistent but dysfunctional mucosal sars cov 2 specific iga and low lung il 1β associate with covid 19 fatal outcome a cross sectional analysis |
| topic | SARS-CoV-2 COVID-19 mucosal immunity IgA severe infection inflammatory cytokine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.842468/full |
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