Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
    • WoS Reviewer Recognition Service
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
    • WoS Reviewer Recognition Service
  • Alerts
  • Subscriptions

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

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, James Smith, Quan-Zhen Li, Susan Waserman, Christopher J Ryerson, Parameswaran Nair, Terence Ho, Narayanaswamy Balakrishnan, Ishac Nazy, Dawn ME Bowdish, Sarah Svenningsen, Chris Carlsten, Manali Mukherjee
European Respiratory Journal 2022; DOI: 10.1183/13993003.00970-2022
Kiho Son
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rameen Jamil
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abhiroop Chowdhury
2Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada
6equal contribution
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manan Mukherjee
2Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada
6equal contribution
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carmen Venegas
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kate Miyasaki
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kayla Zhang
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zil Patel
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brittany Salter
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Agnes Che Yan Yuen
3Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Soon-Keen Lau
3Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kevin Soon-Keen Lau
Braeden Cowbrough
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine Radford
4Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chynna Huang
4Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melanie Kjarsgaard
4Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Dvorkin-Gheva
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anna Dvorkin-Gheva
James Smith
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Quan-Zhen Li
5Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan Waserman
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher J Ryerson
3Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Parameswaran Nair
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Terence Ho
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Terence Ho
Narayanaswamy Balakrishnan
2Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ishac Nazy
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dawn ME Bowdish
1Department of Medicine, McMaster University, Hamilton, ON, Canada
4Firestone Institute for Respiratory Health, The Research Institute of St. Joes, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Dawn ME Bowdish
Sarah Svenningsen
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chris Carlsten
3Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Chris Carlsten
Manali Mukherjee
1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Manali Mukherjee
  • For correspondence: mukherj@mcmaster.ca
  • Article
  • Info & Metrics
  • PDF
Loading

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-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.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflicts of interest: MM (Manali Mukherjee) is supported by early investigator award from Canadian Institutes of Health Research (CIHR) and Canadian Asthma Allergy and Immunology Foundation (CAAIF). MM reports grants from CIHR, grants from Methapharm Specialty Pharmaceuticals, personal fees from AstraZeneca, GlaxoSmithKline, consultant fees from Novartis, outside the submitted work. SS reports grants from Cyclomedica, personal fees from Arrowhead Pharmaceuticals, honorarium for lectures from AZ, honorarium for lectures from Novartis, and honorarium for lectures from Polarean, outside the submitted work. SW reports grants and consulting fees from Alk Abello, grants from Canadian Allergy, Asthma, and Immunology Foundation, Aimmune, grants and consulting fees from CSL Behring, grants from Takeda, personal and consulting fees from AZ, personal and consulting fees from GSK, consulting fees from Novartis, consulting and personal fees from Sanofi, consulting and personal fees from Medexus, consulting and personal fees from Miravo Health, consulting fees from AbbVie, consulting and personal fees from Bausch Lomb, outside of the submitted work. SW reports being president for CAAIF, board of directors for Asthma Canada, and medical advisor for Food Allergy Canada. PN reports grants and personal fees from AZ, grants and personal fees from Teva, grants and personal fees from Sanofi, personal fees from GSK, personal fees from Equillium, personal fees from Arrowhead pharma, grants from Foresee, grants from Cyclomedica, outside the submitted work. DB reports grants from COVID-19 Immunity Task Force / Public Health Agency of Canada, grants from National Science and Engineering Research Council (NSERC), grants from Canadian Institutes of Health Research, personal fees from AZ Mexico, personal fees for invited presentations from academic institutions, outside the submitted work. DB reports being on the board of directors for Lung Health Foundation and being an expert witness testimony for the Government of Canada. KS, RJ, AC, Manan Mukherjee, CV, KM, KZ, ZP, BS, AY, KL, BC, KR, CH, MK, ADG, JS, QL, CR, TH, NB, IN, CC have nothing to report.

  • Received May 10, 2022.
  • Accepted August 4, 2022.
  • Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
View Full Text

ERS Members

myERS - ERS members : log in with your myERS username and password.

INDIVIDUALS

Log in Login as an individual user.

Forgot your username or password?

LIBRARY USERS

Log in through your institution

If your library has a subscription, you may already be logged in via your IP address. Otherwise you may be able to log in via one of the following routes.
You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.
If you think you should have access, please contact your librarian or email journals@ersnet.org

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top
View this article with LENS
Vol 62 Issue 5 Table of Contents
European Respiratory Journal: 62 (5)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
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, James Smith, Quan-Zhen Li, Susan Waserman, Christopher J Ryerson, Parameswaran Nair, Terence Ho, Narayanaswamy Balakrishnan, Ishac Nazy, Dawn ME Bowdish, Sarah Svenningsen, Chris Carlsten, Manali Mukherjee
European Respiratory Journal Jan 2022, 2200970; DOI: 10.1183/13993003.00970-2022

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
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, James Smith, Quan-Zhen Li, Susan Waserman, Christopher J Ryerson, Parameswaran Nair, Terence Ho, Narayanaswamy Balakrishnan, Ishac Nazy, Dawn ME Bowdish, Sarah Svenningsen, Chris Carlsten, Manali Mukherjee
European Respiratory Journal Jan 2022, 2200970; DOI: 10.1183/13993003.00970-2022
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
  • Info & Metrics
  • PDF

Subjects

  • Respiratory infections and tuberculosis
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Mortality surrogates in combined pulmonary fibrosis and emphysema
  • Inhaled GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune PAP patients
  • Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in People With Cystic Fibrosis and at Least One F508del Allele: 144-Week Interim Results From a 192-Week Open-label Extension Study
Show more Original research article

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society