Absence of Type I Interferon Autoantibodies or Significant Interferon Signature Alterations in Adults With Post-COVID-19 Syndrome

Martin Achleitner; Nina K Mair; Juliane Dänhardt; Romina Kardashi; Milo A Puhan; Irene A Abela; Nicole Toepfner; Katja de With; Waldemar Kanczkowski; Natalia Jarzebska; Roman N Rodionov; Christine Wolf; Min Ae Lee-Kirsch; Charlotte Steenblock; Benjamin G Hale; Stefan R Bornstein

doi:10.1093/ofid/ofad641

Absence of Type I Interferon Autoantibodies or Significant Interferon Signature Alterations in Adults With Post-COVID-19 Syndrome

Open Forum Infect Dis. 2023 Dec 19;11(1):ofad641. doi: 10.1093/ofid/ofad641. eCollection 2024 Jan.

Authors

Martin Achleitner¹, Nina K Mair^{2

3}, Juliane Dänhardt¹, Romina Kardashi¹, Milo A Puhan⁴, Irene A Abela^{2

5}, Nicole Toepfner⁶, Katja de With⁷, Waldemar Kanczkowski¹, Natalia Jarzebska¹, Roman N Rodionov¹, Christine Wolf⁶, Min Ae Lee-Kirsch⁶, Charlotte Steenblock¹, Benjamin G Hale², Stefan R Bornstein^{1

8

9}

Affiliations

¹ Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
² Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
³ Life Science Zurich Graduate School, ETH and University of Zurich, Zurich, Switzerland.
⁴ Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
⁵ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
⁶ Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁷ Division of Infectious Diseases, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
⁹ Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich, Zurich, Switzerland.

Abstract

Genetic defects in the interferon (IFN) system or neutralizing autoantibodies against type I IFNs contribute to severe COVID-19. Such autoantibodies were proposed to affect post-COVID-19 syndrome (PCS), possibly causing persistent fatigue for >12 weeks after confirmed SARS-CoV-2 infection. In the current study, we investigated 128 patients with PCS, 21 survivors of severe COVID-19, and 38 individuals who were asymptomatic. We checked for autoantibodies against IFN-α, IFN-β, and IFN-ω. Few patients with PCS had autoantibodies against IFNs but with no neutralizing activity, indicating a limited role of type I IFNs in PCS pathogenesis. In a subset consisting of 28 patients with PCS, we evaluated IFN-stimulated gene activity and showed that it did not correlate with fatigue. In conclusion, impairment of the type I IFN system is unlikely responsible for adult PCS.

Keywords: COVID-19; autoantibodies; interferon; post–COVID-19 syndrome.