Autoimmunity is a hallmark of post-COVID syndrome, 2022, Rojas et al

[Andy]

Abstract

Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days.

Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5–10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.

Open access, https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03328-4

 

[Jonathan Edwards]

This sort of mishmash of results basically means they didn't find anything interesting I suspect.

 

[Hutan]

After quality control filtering of microarray, 116 IgG and 104 IgM antibodies were included in the final analysis.

More than 10% of the patients were positive for IL2, CD8B, and Thyroglobulin IgG autoantibodies (Fig. 1A). Other anti-cytokine IgG autoantibodies were present in 5–10% of the patients.

Antibodies were considered “positive” if NFI was > 2 SD above the average NFI for pre-pandemic controls for that antigen.

The figure below will be hard to see, but the detail probably isn't important. The three black dots across the top are 10% markers. IgM are in blue, IgG are in orange. There's a list of autoantibodies, and the percentage of Long Covid patients testing positive to them is shown by the horizontal bars.

You can see that for a few IgG autoantibodies, around 10% of the Long Covid patients tested positive for them, and there's quite a few autoantibodies where only about 5% tested positive for them. But there's no single autoantibody that really stands out as being present in a majority of the Long Covid patients.



So, yes, a mishmash.

Latent autoimmunity (i.e., one IgG autoantibody) and PolyA (i.e., two or more IgG autoantibodies) were found in 83% and 62% of patients, respectively.

83% of the Long Covid patients having elevated levels of at least one autoantibody sounds impressive, but I don't think they tell us what percentage of the controls also have elevated levels of at least one autoantibody.

In summary, autoimmunity is a hallmark of PCS

I don't see how they can say that, without telling us how many of the healthy controls had elevated levels of at least one autoantibody.

I suppose it's possible that they didn't find the crucial autoantibody that the majority of the Long Covid patients would test positive to, because they didn't test for it.

 

[Hutan]

Just trying to understand the prevalence of autoantibodies in health people - possibly I've done this before, or read something about this already, but forgotten about it.

There's this 2016 paper, Silosi et al,
The role of autoantibodies in health and disease

Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies, called natural antibodies, are particularly IgM isotype, are considered natural autoantibodies (NAA), displaying a moderate affinity for self-antigens. Although incidence of NAA in healthy individuals is not reported, it is established that autoreactive antibodies and B-cells, as well as autoreactive T-cells, are present in healthy persons. The functional abilities of NAA are not clear but is well accepted that they may participate in a variety of activities, such as maintenance of immune homeostasis, regulation of the immune response, resistance to infections, transport and functional modulation of biologically active molecules.

On the other hand, specific adaptive immune responses through high-affinity, class-switched IgG autoantibodies, which bind self-proteins, can cause tissue damage or malfunctions, inducing autoimmune diseases.

The new technology that allows for more autoantibody screening may further enhance the clinical utility of autoantibody tests, making it possible to diagnose autoimmune disease in its early stages and to intervene before installing injuries. The aim of this review paper is to succinctly analyze the progress in the physiological role and regulatory significance of natural autoantibodies in health and disease.

They seem to be saying, yes, healthy individuals do have autoantibodies, and these autoantibodies can actually be useful- helping with immune responses, among other things. So, if you were comparing Long Covid patients with healthy controls, it sounds a though it would be important to compare with people who have had a Covid infection a similar amount of time ago, but don't have ongoing symptoms.

Interestingly, Silosi et al seem to be suggesting that the useful autoantibodies are mostly IgM, whereas the IgG autoantibodies are more likely to cause harm.

Anyone who knows more about this, feel free to jump in anytime.

 

[Hutan]

I'm taking the thread off the topic of this study, I'll head-on over to the discussion thread
The possibility of autoimmunity or auto-reactivity in ME/CFS

 

[Jonathan Edwards]

They seem to be saying, yes, healthy individuals do have autoantibodies, and these autoantibodies can actually be useful- helping with immune responses, among other things. So, if you were comparing Long Covid patients with healthy controls, it sounds a though it would be important to compare with people who have had a Covid infection a similar amount of time ago, but don't have ongoing symptoms.

Yes, we have known from the outset that autoantibodies occur in normal healthy people but less frequently. The stuff about them being useful is speculation. We just know they are there. We probably know why they are too but that gets complicated. They are almost certainly noise rather than function.

You are absolutely right that the study needs not just normal controls but matched controls who have had Covid and are well. If the authors do not give control rates, as you indicate, then the paper is worthless and probably irresponsible.

 

[Hutan]

Yes, we have known from the outset that autoantibodies occur in normal healthy people but less frequently.

Given, as you say elsewhere, that it's basic immunology, it is really hard to understand how the 8 authors of the paper could have declared 'Autoimmunity is a hallmark of post-Covid syndrome'. Particularly when most of them work either in a Centre for Autoimmune Diseases Research or a Department of Immunology.

It's even harder to understand how the two peer reviewers and the editors can have allowed this paper to be published with the results as they are and the title as it is.

Submitted manuscripts will generally be reviewed by two or more experts who will be asked to evaluate whether the manuscript is scientifically sound and coherent, whether it duplicates already published work, and whether or not the manuscript is sufficiently clear for publication. The Editors will reach a decision based on these reports and, where necessary, they will consult with members of the Editorial Board.

Sadly, I don't think it's possible to post a comment in the Journal. (?).

 

[Jonathan Edwards]

Particularly when most of them work either in a Centre for Autoimmune Diseases Research or a Department of Immunology.

This simply a symptom of how much biomedical research has collapsed in the last twenty years.
The situation is the same at UCL now. Nobody has a clue what they are doing. Paper after paper is produced based on gibberish. This is a real change. It was noted by James Le Fanu in his Rise and Fall of Modern Medicine. Something went wrong in the incentive structure around 1985 that by 2000 had destroyed the intellectual base.

The straw that broke the camel's back was the commercialisation of the literature system. There is no longer meaningful peer review most of the time.

The situation is quite similar to the way the kleptocracy has taken over public services in socialist (or for that matter centrist) countries. It suits those who form the self-perpetuating oligarchy.

You might think this extreme but note that despite a string of groundbreaking developments in autoimmunity in the 1990s, for disorders like RA nothing new has emerged in twenty years now. Things have moved forward in multiple sclerosis simply because it took time to catch up with progress for other diseases. (The recent finding on EBV may be the one exception to all this.)

 

[FMMM1]

evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies.

I haven't looked at this, and my knowledge is very limited. I'm wondering about the quality of the tests; I've seen comments here that some studies use linear peptide arrays. So the results are unreliable to begin with.

There's a thread here* re a better technique and I think Solve funded one of the Yale group to look for autoantibodies in ME.

So there are ways to run reliable tests - begs the question of why supposed peer reviewed journals are publishing poor quality studies --- commercialisation of the literature system seems a reasonable suggestion. Why aren't alternatives taking off ---?


*https://www.s4me.info/threads/reap-...-the-human-exoproteome-2021-wang-et-al.20747/

 

[bobbler]

This simply a symptom of how much biomedical research has collapsed in the last twenty years.
The situation is the same at UCL now. Nobody has a clue what they are doing. Paper after paper is produced based on gibberish. This is a real change. It was noted by James Le Fanu in his Rise and Fall of Modern Medicine. Something went wrong in the incentive structure around 1985 that by 2000 had destroyed the intellectual base.

The straw that broke the camel's back was the commercialisation of the literature system. There is no longer meaningful peer review most of the time.

The situation is quite similar to the way the kleptocracy has taken over public services in socialist (or for that matter centrist) countries. It suits those who form the self-perpetuating oligarchy.

You might think this extreme but note that despite a string of groundbreaking developments in autoimmunity in the 1990s, for disorders like RA nothing new has emerged in twenty years now. Things have moved forward in multiple sclerosis simply because it took time to catch up with progress for other diseases. (The recent finding on EBV may be the one exception to all this.)

I don't find it extreme and I'm not in the medical profession just watching and experiencing it. It reflects what I see. The 'get to the bottom of it' seems to be actively the opposite of the NHS drives of recent years (more 'mass standardisation'). I'd add in the change to the REF vs RAE 2008 in as far as using citations over objective assessments and the way that impact has ended up being implemented (which many academics found hard to get to grips with) - which whilst perhaps with some worthy ideas behind it, had led to 'easy to understand' paradigms over 'correct and good methodology' getting a nice foothold.

It's become like social media 'likes', politics and networking can drive little kingdoms with no hard quality-assessment to many it transparent. Added to reduced peer review on this basis and the hierarchical issues/power bases implicit in UK systems. As they say in business 'culture is strategy'.

 

[Simon M]

The straw that broke the camel's back was the commercialisation of the literature system. There is no longer meaningful peer review most of the time.

Ah, now that would be the late Robert Maxwell's great contribution with his Pergamon Press if I have it right.