Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
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- creativework.keywords - en
- Respiratory infections and tuberculosis
- dc.contributor.author
- Son, Kiho
- Jamil, Rameen
- Chowdhury, Abhiroop
- Mukherjee, Manan
- Venegas, Carmen
- Miyasaki, Kate
- Zhang, Kayla
- Patel, Zil
- Salter, Brittany
- Yuen, Agnes Che Yan
- Lau, Kevin Soon-Keen
- Cowbrough, Braeden
- Radford, Katherine
- Huang, Chynna
- Kjarsgaard, Melanie
- Dvorkin-Gheva, Anna
- Smith, James
- Li, Quan-Zhen
- Waserman, Susan
- Ryerson, Christopher J.
- Nair, Parameswaran
- Ho, Terence
- Balakrishnan, Narayanaswamy
- Nazy, Ishac
- Bowdish, Dawn M. E.
- Svenningsen, Sarah
- Carlsten, Chris
- Mukherjee, Manali
- dc.date.accessioned
- 2024-01-10T21:07:02Z
- dc.date.available
- 2024-01-10T21:07:02Z
- dc.date.issued
- 2023
- dc.description.abstract - en
- BACKGROUND: Autoimmunity has been reported in patients with severe coronavirus disease 2019 (COVID-19). We investigated whether anti-nuclear/extractable-nuclear antibodies (ANAs/ENAs) were present up to a year after infection, and if they were associated with the development of clinically relevant post-acute sequalae of COVID-19 (PASC) symptoms. METHODS: A rapid-assessment line immunoassay was used to measure circulating levels of ANAs/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6 and 12 months post-recovery. Patient-reported fatigue, cough and dyspnoea were recorded at each time point. Multivariable logistic regression model and receiver operating curves were used to test the association of autoantibodies with patient-reported outcomes and pro-inflammatory cytokines. RESULTS: Compared to age- and sex-matched healthy controls (n=22) and those who had other respiratory infections (n=34), patients with COVID-19 had higher detectable ANAs at 3 months post-recovery (p<0.001). The mean number of ANA autoreactivities per individual decreased between 3 and 12 months (from 3.99 to 1.55) with persistent positive titres associated with fatigue, dyspnoea and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p<0.028, area under the curve (AUC) 0.86) and dyspnoea (p<0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor (TNF)-α and C-reactive protein predicted the elevated ANAs at 12 months. TNF-α, D-dimer and interleukin-1β had the strongest association with symptoms at 12 months. Regression analysis showed that TNF-α predicted fatigue (β=4.65, p=0.004) and general symptomaticity (β=2.40, p=0.03) at 12 months. INTERPRETATION: Persistently positive ANAs at 12 months post-COVID are associated with persisting symptoms and inflammation (TNF-α) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.
- dc.identifier.doi
- https://doi.org/10.1183/13993003.00970-2022
- dc.identifier.issn
- 0903-1936
- dc.identifier.pubmedID
- 36137590
- dc.identifier.uri
- https://open-science.canada.ca/handle/123456789/1675
- dc.language.iso
- en
- dc.publisher
- European Respiratory Society
- dc.rights - en
- Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
- dc.rights - fr
- Creative Commons Attribution-Pas d’Utilisation Commerciale 4.0 International (CC BY-NC 4.0)
- dc.rights.openaccesslevel - en
- Gold
- dc.rights.openaccesslevel - fr
- Or
- dc.rights.uri - en
- https://creativecommons.org/licenses/by-nc/4.0/
- dc.rights.uri - fr
- https://creativecommons.org/licenses/by-nc/4.0/deed.fr
- dc.subject - en
- Health
- dc.subject - fr
- Santé
- dc.subject.en - en
- Health
- dc.subject.fr - fr
- Santé
- dc.title - en
- Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
- dc.type - en
- Article
- dc.type - fr
- Article
- local.acceptedmanuscript.articlenum
- 2200970
- local.article.journalissue
- 1
- local.article.journaltitle
- European Respiratory Society
- local.article.journalvolume
- 61
- local.pagination
- 1-14
- local.peerreview - en
- Yes
- local.peerreview - fr
- Oui
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