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.

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.

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.