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Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms

2022; European Respiratory Society; Linguagem: Inglês

10.1183/13993003.00970-2022

1399-3003

Kiho Son, Rameen Jamil, Abhiroop Chowdhury, Manan Mukherjee, Carmen Venegas, Kate Miyasaki, Kayla Zhang, Zil Patel, Brittany Salter, Agnes Che Yan Yuen, Kevin Soon-Keen Lau, Braeden Cowbrough, Katherine Radford, Chynna Huang, Melanie Kjarsgaard, Anna Dvorkin‐Gheva, J. L. Smith, Quan‐Zhen Li, Susan Waserman, Christopher J. Ryerson, Parameswaran Nair, Terence Ho, N. Balakrishnan, Ishac Nazy, Dawn M. E. Bowdish, Sarah Svenningsen, Chris Carlsten, Manali Mukherjee,

Inflammasome and immune disorders

Background Autoimmunity has been reported in patients with severe COVID-19. We investigated whether antinuclear/extractable-nuclear antibodies (ANAs) 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 ANA/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 dyspnea were recorded at each timepoint. Multivariable logistic regression model and receiver-operating curves (ROC) 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 from 3 to 12 months (3.99 to 1.55) with persistent positive titers associated with fatigue, dyspnea, and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p<0.028, AUC=0.86) and dyspnea (p<0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNFα) and C-reactive protein predicted the elevated ANAs at 12 months. TNFα, D-dimer, and IL-1β had the strongest association with symptoms at 12 months. Regression analysis showed TNFα 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 (TNFα) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.