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

Candie Joly; Delphine Desjardins; Raphael Porcher; Hélène Péré; Thomas Bruneau; Qian Zhang; Paul Bastard; Aurélie Cobat; Léa Resmini; Olivia Lenoir; Laurent Savale; Camille Lécuroux; Céline Verstuyft; Anne-Marie Roque-Afonso; David Veyer; Gabriel Baron; Matthieu Resche-Rigon; Philippe Ravaud; Jean-Laurent Casanova; Roger Le Grand; Olivier Hermine; Pierre-Louis Tharaux; Xavier Mariette

doi:10.3389/fimmu.2023.1250214

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

Front Immunol. 2023 Nov 21:14:1250214. doi: 10.3389/fimmu.2023.1250214. eCollection 2023.

Authors

Candie Joly^#¹, Delphine Desjardins^#¹, Raphael Porcher^#², Hélène Péré^#³, Thomas Bruneau⁴, Qian Zhang^{5

6

7}, Paul Bastard^{5

6

7}, Aurélie Cobat^{5

6

7}, Léa Resmini⁸, Olivia Lenoir⁸, Laurent Savale^{9

10}, Camille Lécuroux¹, Céline Verstuyft¹¹, Anne-Marie Roque-Afonso^{11

12}, David Veyer^{3

4}, Gabriel Baron², Matthieu Resche-Rigon¹³, Philippe Ravaud², Jean-Laurent Casanova^{5

6

7

14}, Roger Le Grand¹, Olivier Hermine^{15

16}, Pierre-Louis Tharaux^#⁸, Xavier Mariette^#^{1

17}

Affiliations

¹ Université Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), UMR1184, Le Kremlin Bicêtre, France.
² Université de Paris, Center of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, AP-HP, Hôpital Hôtel-Dieu, Paris, France.
³ Sorbonne Université and Université de Paris, INSERM, Functional Genomics of Solid Tumors (FunGeST), Centre de Recherche des Cordeliers, Paris, France.
⁴ Service de Microbiologie (Unité de virologie), Assistance Publique Hôpitaux de Paris-Centre (AP-HP-Centre), Hôpital Européen Georges Pompidou, Paris, France.
⁵ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
⁶ University of Paris, Imagine Institute, Paris, France.
⁷ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States.
⁸ Université de Paris, INSERM, Paris Cardiovascular Center (PARCC), Paris, France.
⁹ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.
¹⁰ AP-HP, Centre de Référence de l'Hypertension Pulmonaire, Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, INSERM UMR999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
¹¹ Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Centre de Ressource Biologique Paris-Saclay, Le Kremlin Bicêtre, France.
¹² Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Laboratoire de Virologie, Villejuif, France.
¹³ Centre of Research in Epidemiology and Statistics (CRESS), Université de Paris, INSERM, Hôpital Saint Louis, Paris, France.
¹⁴ Howard Hughes Medical Institute, New York, NY, United States.
¹⁵ Université de Paris, Institut Imagine, INSERM UMR1183, Paris, France.
¹⁶ Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Département d'Hématologie, Paris, France.
¹⁷ Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Rhumatologie, Le Kremlin Bicêtre, France.

^# Contributed equally.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; pneumonia; prospective study; type I interferon.

Copyright © 2023 Joly, Desjardins, Porcher, Péré, Bruneau, Zhang, Bastard, Cobat, Resmini, Lenoir, Savale, Lécuroux, Verstuyft, Roque-Afonso, Veyer, Baron, Resche-Rigon, Ravaud, Casanova, Le Grand, Hermine, Tharaux and Mariette.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Interferon Type I*
Plasma
RNA, Viral
SARS-CoV-2

Substances

Interferon Type I
RNA, Viral
IFNA2 protein, human

Associated data

ClinicalTrials.gov/NCT04331808
ClinicalTrials.gov/NCT04324073
ClinicalTrials.gov/NCT04341584

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This trial was publicly funded (Ministry of Health, Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Assistance Publique – Hôpitaux de Paris Foundation. The high sensitive dosage of IFN was performed thanks to Fondation DORMEUR. The study was in part supported by the mécénat GHU Paris-Centre from AP-HP (to Hélène Péré), grants from the Fondation pour la Recherche Médicale (FRM) (REA202010012514) and Agence Nationale de Recherches sur le Sida and emerging infectious diseases (ANRS) (ANRS0147) from the VINTED sponsorship to Pierre-Louis Tharaux, and grants from Université Paris-Saclay, DIM « One Health » and IDMIT (ANR-11-INBS-0008) to Roger Le Grand.