Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19

August F. Jernbom (), Lovisa Skoglund, Elisa Pin, Ronald Sjöberg, Hanna Tegel, Sophia Hober, Elham Rostami, Annica Rasmusson, Janet L. Cunningham, Sebastian Havervall, Charlotte Thålin, Anna Månberg and Peter Nilsson
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August F. Jernbom: KTH Royal Institute of Technology
Lovisa Skoglund: KTH Royal Institute of Technology
Elisa Pin: KTH Royal Institute of Technology
Ronald Sjöberg: KTH Royal Institute of Technology
Hanna Tegel: KTH Royal Institute of Technology
Sophia Hober: KTH Royal Institute of Technology
Elham Rostami: Uppsala University Hospital
Annica Rasmusson: Uppsala University
Janet L. Cunningham: Uppsala University
Sebastian Havervall: Danderyd Hospital
Charlotte Thålin: Danderyd Hospital
Anna Månberg: KTH Royal Institute of Technology
Peter Nilsson: KTH Royal Institute of Technology

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Autoantibodies have been shown to be implied in COVID-19 but the emerging autoantibody repertoire remains largely unexplored. We investigated the new-onset autoantibody repertoire in 525 healthcare workers and hospitalized COVID-19 patients at five time points over a 16-month period in 2020 and 2021 using proteome-wide and targeted protein and peptide arrays. Our results show that prevalent new-onset autoantibodies against a wide range of antigens emerged following SARS-CoV-2 infection in relation to pre-infectious baseline samples and remained elevated for at least 12 months. We found an increased prevalence of new-onset autoantibodies after severe COVID-19 and demonstrated associations between distinct new-onset autoantibodies and neuropsychiatric symptoms post-COVID-19. Using epitope mapping, we determined the main epitopes of selected new-onset autoantibodies, validated them in independent cohorts of neuro-COVID and pre-pandemic healthy controls, and identified sequence similarities suggestive of molecular mimicry between main epitopes and the conserved fusion peptide of the SARS-CoV-2 Spike glycoprotein. Our work describes the complexity and dynamics of the autoantibody repertoire emerging with COVID-19 and supports the need for continued analysis of the new-onset autoantibody repertoire to elucidate the mechanisms of the post-COVID-19 condition.

Date: 2024
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DOI: 10.1038/s41467-024-53356-5

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