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

• Published in: Frontiers in immunology 2023-11, Vol.14, p.1250214-1250214
• Main Authors: Joly, Candie, Desjardins, Delphine, Porcher, Raphael, Péré, Hélène, Bruneau, Thomas, Zhang, Qian, Bastard, Paul, Cobat, Aurélie, Resmini, Léa, Lenoir, Olivia, Savale, Laurent, Lécuroux, Camille, Verstuyft, Céline, Roque-Afonso, Anne-Marie, Veyer, David, Baron, Gabriel, Resche-Rigon, Matthieu, Ravaud, Philippe, Casanova, Jean-Laurent, Le Grand, Roger, Hermine, Olivier, Tharaux, Pierre-Louis, Mariette, Xavier
• Format: Article
• Language: English
• Subjects: COVID-19; Humans; Interferon Type I; Life Sciences; Plasma; pneumonia; prospective study; RNA, Viral; SARS-CoV-2; type I interferon
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1250214

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. 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. 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. 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. 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. https://clinicaltrials.gov, identifiers NCT04324073, NCT04331808, NCT04341584.