Poster Presentation 16th Lorne Infection and Immunity 2026

Evaluating the prevalence of anti-interferon autoantibodies in post-acute infection syndromes  (132509)

Maddison Cali 1 , Ashley Chong 1 , Tim Spelman 1 , Irene Boo 1 , Marie-Claire Seeley 2 , Celine Gallagher 2 , Annemarie Laumaea 1 , Heidi E Drummer 1 3 4 , Gabriela Khoury 1 4
  1. Burnet Institute, Melbourne, Victoria, Australia
  2. The University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia
  3. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia
  4. Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia

Background: Post-Acute Infection Syndromes (PAIS), including long COVID and Postural Orthostatic Tachycardia Syndrome (POTS), arise following acute infections and are characterised by chronic sequelae. The mechanisms underlying this failure to recover from infection remain unexplained, impacting quality of life. In this study we investigated the role of anti-interferon (anti-IFN) autoantibodies.   

  

Methods: Using a commercial multiplex assay, anti-IFN (α2, β, ω, γ) autoantibodies were measured in biobanked serum or plasma samples from 4 cohorts, healthy volunteers (HV), mild COVID, severe COVID and long COVID. Linear mean regression models were used to assess differences in anti-IFN autoantibody levels between HV and each COVID cohort, adjusting for age and biological sex.  

  

Results: A total of 187 participants were tested, with cohort characteristics of i) HV (n=26, mean 33.9 years [23-70], 92% female); ii) mild COVID (n=67, mean 44.9 years [23-77], 43% female); iii) severe COVID (n= 14, mean 66.4 years [34-95], 21% female); and iv) long COVID (n=80, mean 42.2 years [18-76], 77.5% female). Compared to HV, the mild COVID cohort showed significantly higher levels of autoantibodies to all 4 IFNs (p <0.001). The same was observed in the severe COVID cohort (p ≤0.005) except for anti-IFN-ω. In the long COVID cohort, there was a smaller but statistically significant increase in anti-IFN-β autoantibodies (β =0.27, [95% CI 0.00-0.54], p=0.047). When the long COVID cohort was stratified based on POTS status, no statistically significant increases were observed. 

  

Conclusion: Anti-IFN autoantibodies were elevated in people with mild and severe acute SARS-CoV-2 disease. In long COVID, anti-IFN-β autoantibodies may underlie post-acute sequelae in a subset of people. We are currently developing an assay using Biolayer Interferometry to test the neutralising capacity of the detected anti-IFN autoantibodies. Further investigation is necessary to determine whether neutralising anti-IFN autoantibodies contribute to PAIS, with implications for diagnosis and treatment.