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Sci Transl Med
. 2024 Nov 6;16(772):eadq1789.
doi: 10.1126/scitranslmed.adq1789. Epub 2024 Nov 6. Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19
Benjamin R Babcock 1 , Astrid Kosters 1 , Devon J Eddins 1 , Maria Sophia Baluyot Donaire 2 , Sannidhi Sarvadhavabhatla 2 , Vivian Pae 2 , Fiona Beltran 2 , Victoria W Murray 2 , Gurjot Gill 2 , Guorui Xie 3 4 , Brian S Dobosh 5 , Vincent D Giacalone 5 , Rabindra M Tirouvanziam 5 , Richard P Ramonell 6 , Scott A Jenks 1 , Ignacio Sanz 1 , F Eun-Hyung Lee 6 , Nadia R Roan 3 4 , Sulggi A Lee 2 , Eliver E B Ghosn 1 7
Affiliations
Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti-IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti-IFN-α in the immunopathology of COVID-19 and suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.
. 2024 Nov 6;16(772):eadq1789.
doi: 10.1126/scitranslmed.adq1789. Epub 2024 Nov 6. Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19
Benjamin R Babcock 1 , Astrid Kosters 1 , Devon J Eddins 1 , Maria Sophia Baluyot Donaire 2 , Sannidhi Sarvadhavabhatla 2 , Vivian Pae 2 , Fiona Beltran 2 , Victoria W Murray 2 , Gurjot Gill 2 , Guorui Xie 3 4 , Brian S Dobosh 5 , Vincent D Giacalone 5 , Rabindra M Tirouvanziam 5 , Richard P Ramonell 6 , Scott A Jenks 1 , Ignacio Sanz 1 , F Eun-Hyung Lee 6 , Nadia R Roan 3 4 , Sulggi A Lee 2 , Eliver E B Ghosn 1 7
Affiliations
- PMID: 39504354
- DOI: 10.1126/scitranslmed.adq1789
Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti-IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti-IFN-α in the immunopathology of COVID-19 and suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.