Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19, 2024, Nilsson et al

[EndME]

Now published - link here

Preprint
Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19

Abstract
Autoantibodies have been shown to be implied in COVID-19 but the emerging autoantibody repertoire remains largely unexplored. We investigated the new-onset autoantibody repertoire in 525 healthcare workers and hospitalized COVID-19 patients in five time points over 16 months using proteome-wide and targeted protein and peptide arrays.

Our results show that prevalent new-onset autoantibodies against a wide range of antigens emerged following SARS-CoV-2 infection in relation to pre-infectious baseline samples and remained elevated for at least 12 months. We demonstrated associations between distinct new-onset autoantibodies and neuropsychiatric symptoms post-COVID-19. Using epitope mapping, we determined the main epitopes of selected new-onset autoantibodies, validated them in independent cohorts of neuro-COVID and pre-pandemic healthy controls, and identified molecular mimicry between main epitopes and the conserved fusion peptide of the SARS-CoV-2 Spike glycoprotein.

Our work describes the complexity and dynamics of the autoantibody repertoire emerging with COVID-19 and supports the need for continued analysis of the new-onset autoantibody repertoire to elucidate the mechanisms of the post-COVID-19 condition.

https://www.medrxiv.org/content/10.1101/2024.02.15.24302857v1

 

[Jonathan Edwards]

I suspect that they have simply demonstrated that people with covid develop antibodies to Covid. Peptides are not a good way to look for autoantibodies of clinical relevance.

 

[SNT Gatchaman]

Now published as

Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19
Jernbom, August F.; Skoglund, Lovisa; Pin, Elisa; Sjöberg, Ronald; Tegel, Hanna; Hober, Sophia; Rostami, Elham; Rasmusson, Annica; Cunningham, Janet L.; Havervall, Sebastian; Thålin, Charlotte; Månberg, Anna; Nilsson, Peter

Autoantibodies have been shown to be implied in COVID-19 but the emerging autoantibody repertoire remains largely unexplored. We investigated the newonset autoantibody repertoire in 525 healthcare workers and hospitalized COVID-19 patients at five time points over a 16-month period in 2020 and 2021 using proteome-wide and targeted protein and peptide arrays.

Our results show that prevalent new-onset autoantibodies against a wide range of antigens emerged following SARS-CoV-2 infection in relation to pre-infectious baseline samples and remained elevated for at least 12 months. We found an increased prevalence of new-onset autoantibodies after severe COVID-19 and demonstrated associations between distinct new-onset autoantibodies and neuropsychiatric symptoms post-COVID-19. Using epitope mapping, we determined the main epitopes of selected new-onset autoantibodies, validated them in independent cohorts of neuro-COVID and pre-pandemic healthy controls, and identified sequence similarities suggestive of molecular mimicry between main epitopes and the conserved fusion peptide of the SARS-CoV-2 Spike glycoprotein.

Our work describes the complexity and dynamics of the autoantibody repertoire emerging with COVID-19 and supports the need for continued analysis of the new-onset autoantibody repertoire to elucidate the mechanisms of the post-COVID-19 condition.

Link | PDF (Nature Communications) [Open Access]

 

[SNT Gatchaman]

While previous studies have indicated the existence of new-onset autoantibodies in COVID-19 15,16 and in other pulmonary infections, we have systematically charted the temporal dynamics of the emerging self-directed humoral response in COVID-19 and showed that 60% of new-onset autoantibodies remained elevated for at least 12 months after infection.

The detected new-onset autoantibodies target a wide range of antigens across the proteome, illustrating the breadth of the autoantibody response emerging after COVID-19.

The dynamics of detected new-onset autoantibodies followed three distinct patterns: stable, transient, and delayed onset.

As anti-IFN IgG is implied in severe COVID-19, we specifically characterized the new-onset anti-IFN IgG response in our study. Considering all IFN subtypes, we found new-onset anti-IFN IgG in 3% of the baseline seronegative cohort, mainly consisting of anti-type I IFN IgG.

Since neurological symptoms after COVID-19 are commonly occurring and often debilitating, we made directed efforts in understanding this group of symptoms post-COVID-19. We found three newonset autoantibodies associated with increased severity of neuropsychiatric symptoms post-COVID-19: anti-CALU, MYO16, and SNURF IgG. CALU is a membrane-bound or secreted calcium-binding protein mainly expressed in the heart and skeletal muscle. MYO16 is a cytoplasmic unconventional myosin with enhanced brain expression, and may be involved in the extension of neuronal membrane processes. SNURF is a small (71 aa) nuclear protein of unknown function, primarily expressed in brain and muscle tissues and cardiomyocytes.

Spoiler: GeneCards

CALU
MYO16
SNURF

Our epitope mapping identified the main epitopes of five autoantigens. These epitopes showed a marked increase in reactivity after infection. Among these, the main epitopes of TRIM63 and CCDC63 displayed a sequence alignment to the fusion peptide of the SARS-CoV2 spike glycoprotein.

 

[SNT Gatchaman]

Despite not showing any sequence similarity with SARS-CoV-2, anti-SNURF IgG emerged in 9% of HCW (n = 40) and 20% of hospitalized COVID-19 patients (n = 9). Furthermore, antibodies against the main epitope of SNURF (aa 50–64) were validated in the blood and CSF of patients with neuro-COVID (compared to pre-pandemic HCs). Our detected correlation of autoantibody levels in the blood and CSF corroborates findings of blood-brain barrier disruption in patients with cognitive impairment post-COVID-19.

Furthermore, anti-SNURF IgG was by far the most common autoantibody increasing at vaccination. […] our study does not provide any evidence linking the herein-detected autoantibodies with any adverse effects following vaccination.

In summary, our study shows that new-onset autoantibodies are prevalent and persistent following mild to severe COVID-19 and correspond to disease severity. Furthermore, some are found to be associated with neuropsychiatric symptoms post-COVID-19 and could be detected in both plasma and CSF of patients with neuro-COVID. In addition, we demonstrate that anti-TRIM63 and anti-CCDC63 IgG develop in 10% of the study cohort and reveal their main epitopes using epitope mapping. The main epitopes display sequence similarities indicative of molecular mimicry with the highly conserved fusion peptide of the SARS-CoV-2 Spike glycoprotein, which is essential for viral entry and the target of broadly neutralizing antibodies. Conversely, anti-SNURF IgG is highly prevalent without evidence of molecular mimicry, which may indicate epitope spreading to nuclear antigens.

 

[Turtle]

I suppose lying down won't help against autoantibodies.
Or is my knowledge lacking here too?

 

[Jonathan Edwards]

I suppose lying down won't help against autoantibodies.
Or is my knowledge lacking here too?

I wouldn't worry too much. I doubt there are any of importance.
The things you are li'ble to read in the bible, they ain't necessarily so.

 

[Turtle]

I wouldn't worry too much. I doubt there are any of importance.
The things you are li'ble to read in the bible, they ain't necessarily so.

Thanks for reassuring me. Genetics isn't my thing, that's obvious.
Took me a while to figure out the second sentence. Before the crack of dawn, it dawned on me you were singing a George Gershwin song to me: how nice of you.

 

[Dolphin]

10-item thread on this
https://threadreaderapp.com/thread/1846900048090517601.html

 

[Dolphin]

An author did a thread but blocked responses so it doesn’t look like the Thread unroll tool works on it.

https://twitter.com/user/status/1847297880668741697