More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients - Archive ouverte HAL
Article Dans Une Revue Frontiers in Immunology Année : 2023

More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients

1 IDMIT - Infectious Diseases Models for Innovative Therapies
2 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
3 UPCité - Université Paris Cité
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
6 IB-CAS - Institute of Botany [Beijing]
7 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
8 Hôpital Necker - Enfants Malades [AP-HP]
9 Rockefeller University [New York]
10 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
11 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
12 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
13 CESP - Centre de recherche en épidémiologie et santé des populations
14 Service de Génétique Moléculaire Pharmacogénétique et Hormonologie [CHU Bicêtre]
15 Physiopathologie et traitement des maladies du foie
16 Hôpital Paul Brousse
17 Hôpital Hôtel-Dieu [Paris]
18 ECSTRRA [CRESS - U1153 / UMR_A 1125] - Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé
19 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
20 HHMI - Howard Hughes Medical Institute
21 INSERM - Institut National de la Santé et de la Recherche Médicale
22 UFR Médecine UPCité - UFR Médecine [Santé] - Université Paris Cité

Résumé

Background The clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection. Objective To study the link between change in blood IFN-α2 level and plasma SARS-Cov2 viral load over time and subsequent death in patients with severe and critical COVID-19. Methods One hundred and forty patients from the CORIMUNO-19 cohort hospitalized with severe or critical COVID-19 pneumonia, all requiring oxygen or ventilation, were prospectively studied. Blood IFN-α2 was evaluated using the Single Molecule Array technology. Anti-IFN-α2 auto-Abs were determined with a reporter luciferase activity. Plasma SARS-Cov2 viral load was measured using droplet digital PCR targeting the Nucleocapsid gene of the SARS-CoV-2 positive-strand RNA genome. Results Although the percentage of plasmacytoid dendritic cells was low, the blood IFN-α2 level was higher in patients than in healthy controls and was correlated to SARS-CoV-2 plasma viral load at entry. Neutralizing anti-IFN-α2 auto-antibodies were detected in 5% of patients, associated with a lower baseline level of blood IFN-α2. A longitudinal analysis found that a more rapid decline of blood IFN-α2 was observed in fatal versus surviving patients: mortality HR=3.15 (95% CI 1.14–8.66) in rapid versus slow decliners. Likewise, a high level of plasma SARS-CoV-2 RNA was associated with death risk in patients with severe COVID-19. Conclusion These findings could suggest an interest in evaluating type 1 IFN treatment in patients with severe COVID-19 and type 1 IFN decline, eventually combined with anti-inflammatory drugs. Clinical trial registration https://clinicaltrials.gov , identifiers NCT04324073, NCT04331808, NCT04341584.
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hal-04361184 , version 1 (23-08-2024)

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Candie Joly, Delphine Desjardins, Raphael Porcher, Hélène Péré, Thomas Bruneau, et al.. More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients. Frontiers in Immunology, 2023, 14, pp.1250214. ⟨10.3389/fimmu.2023.1250214⟩. ⟨hal-04361184⟩
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