Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms, 2022, Mukherjee et al

[Wyva]

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.

Paywall: https://erj.ersjournals.com/content/early/2022/08/04/13993003.00970-2022

 

[Hutan]

Canadian study, unfortunately with a paywall.

Link to an article about it
https://www.cidrap.umn.edu/news-per...ifficulty-exercising-noted-1-year-after-covid

In the first study, a team led by McMaster University researchers in Canada obtained blood samples from 106 people who tested positive for COVID-19 from August 2020 to September 2021. They also asked participants about long-COVID symptoms 3, 6, and 12 months after recovery.

Twenty-two healthy volunteers and 34 people who had recovered from a non-COVID respiratory infection served as comparison groups.

At 3 and 6 months, nearly 80% of the COVID-19 survivors had at least two antibodies that target healthy cells and tissues and contribute to autoimmune diseases, falling to 41% after 1 year. In comparison, most healthy volunteers had no evidence of these antibodies, while those who had recovered from a non-COVID illness had relatively low levels.

From 21% to 30% of COVID-19 patients—most who still had shortness of breath and fatigue—had specific antibodies (called anti-U1-snRNP and anti-SS-B/La autoantibodies) and proteins that cause inflammation (TNFα cytokines) at 1 year.

That separation between (severe) Covid-19 survivors and healthy volunteers (at 6 months 80%, at 1 year 41% versus 'most healthy volunteers had no evidence of these antibodies') sounds interesting. As does the link between patients having the two named antibodies and fatigue.

I would have thought there would be a study looking at antibodies to U1-snRNP in ME/CFS, although in a quick search I didn't find one.

We have this, where it's suggested that the loss of U1 snRNP affects glycolysis.
Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS, 2021, Jourdain et al