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Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms.
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 Me; Svenningsen, Sarah; Carlsten, Chris; Mukherjee, Manali.
  • Son K; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Jamil R; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Chowdhury A; Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada.
  • Mukherjee M; equal contribution.
  • Venegas C; Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada.
  • Miyasaki K; equal contribution.
  • Zhang K; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Patel Z; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Salter B; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Yuen ACY; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Lau KS; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Cowbrough B; Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
  • Radford K; Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
  • Huang C; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Kjarsgaard M; Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
  • Dvorkin-Gheva A; Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
  • Smith J; Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
  • Li QZ; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Waserman S; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Ryerson CJ; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
  • Nair P; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Ho T; Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
  • Balakrishnan N; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Nazy I; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Bowdish DM; Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada.
  • Svenningsen S; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Carlsten C; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Mukherjee M; Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
Eur Respir J ; 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: covidwho-2235807
ABSTRACT

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-1ß had the strongest association with symptoms at 12 months. Regression analysis showed TNFα predicted fatigue (ß=4.65, p=0.004) and general symptomaticity (ß=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.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico Tópicos: Covid persistente Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Artigo País de afiliação: 13993003.00970-2022

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Texto completo
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico Tópicos: Covid persistente Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Artigo País de afiliação: 13993003.00970-2022