Similar Kinetics of Pulmonary SARS-CoV-2 Load in Intensive Care Unit Patients with COVID-19 Pneumonia with or Without Autoantibodies Neutralizing Type I Interferons.

Autor: Le Stang V; Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France., Bastard P; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France.; Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistante Publique-Hôpitaux de Paris (AP-HP), Paris, EU, France., Langouet E; Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France., Pineton de Chambrun M; Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France., Chommeloux J; Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France., Gervais A; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France., Bizien L; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France., Puel A; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France., Cobat A; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France., Mayaux J; Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique- Hôpitaux de Paris, Médecine Intensive Réanimation (Département 'R3S') and Sorbonne Université, INSERM, UMRS1158 Neurophysiologie respiratoire expérimentale et clinique, Paris, France., Demoule A; Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique- Hôpitaux de Paris, Médecine Intensive Réanimation (Département 'R3S') and Sorbonne Université, INSERM, UMRS1158 Neurophysiologie respiratoire expérimentale et clinique, Paris, France., Casanova JL; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France.; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France.; Howard Hughes Medical Institute, New York, NY, USA., Boutolleau D; Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Virologie, Centre National de Référence Herpèsvirus (laboratoire associé), Sorbonne Université, INSERM U1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France., Combes A; Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.; INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Paris, France., Burrel S; Université de Bordeaux, CNRS UMR 5234, Fundamental Microbiology and Pathogenicity, Hôpital Universitaire de Bordeaux, Service de Virologie, Bordeaux, France., Luyt CE; Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France. charles-edouard.luyt@aphp.fr.; INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Paris, France. charles-edouard.luyt@aphp.fr.; Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, Paris Cedex 13, 75651, France. charles-edouard.luyt@aphp.fr.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2024 Nov 20; Vol. 45 (1), pp. 45. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1007/s10875-024-01839-x
Abstrakt: Purpose: The pathogenesis of life-threatening coronavirus disease 2019 (COVID-19) pneumonia in ICU patients can involve pre-existing auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs). The impact of these auto-Abs on SARS-CoV-2 clearance in the lower respiratory tract (LRT) is unclear.
Methods: We performed a retrospective study in 99 ICU patients with COVID-19 pneumonia between March and May 2020. LRT SARS-CoV-2 load (intensity and duration) was analyzed according to the presence or not of circulating auto-Abs neutralizing type I IFNs.
Results: Among the 99 included patients, 38 (38%) were positive for auto-Abs neutralizing type I IFNs, with 5 (5%) harboring auto-Abs neutralizing IFN-α2 at any concentration, while 33 (33%) had auto-Abs neutralizing only IFN-ω at the lower concentration. SARS-CoV-2 load in the LRT and duration of viral shedding, were similar in patients with or without auto-Abs neutralizing type I IFNs. Patients with auto-Abs had the same mortality than those without auto-Abs, despite greater occurrence of renal failure and ECMO support, and longer duration of mechanical ventilation and ICU stay.
Conclusion: In summary, 5% of patients with critical COVID-19 pneumonia carried auto-Abs neutralizing IFN-α2, while about 1/3 harbored auto-Abs neutralizing low concentrations of IFN-ω. The detection of either type of auto-Abs did not impact LRT viral clearance and mortality, although it was associated with greater morbidity and a longer hospitalization. These findings suggest that similar albeit hitherto unknown mechanisms of disease drive critical COVID-19 pneumonia in patients without auto-Abs against type I IFNs.
Competing Interests: Declarations. Ethics Approval and Consent to Participate: In accordance with current French law, informed written consent for demographic, physiologic and hospital-outcome data analyses was not obtained because this observational study did not modify existing diagnostic or therapeutic strategies. Nonetheless, patients and/or relatives were informed about the anonymous data collection and told that they could decline inclusion. The protocol was approved by the ethics committee of the Société de Réanimation de Langue Française (registration no. CE-SRLF-2093) and the database is registered with the Commission Nationale de l’Informatique et des Libertés (CNIL, registration no. 1950673). Competing Interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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