Preprint: Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae, 2022, Swank et al

The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies.

We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers. Strikingly, we detect SARS-CoV-2 spike antigen in a majority of PASC patients up to 12 months post-diagnosis, suggesting the presence of an active persistent SARS-CoV-2 viral reservoir.

Furthermore, temporal antigen profiles for many patients show the presence of spike at multiple time points over several months, highlighting the potential utility of the SARS-CoV-2 full spike protein as a biomarker for PASC.

Preprint

 

They found spike in 60% of 37 PASC patients' plasma, at some point 2-12 months post-Covid, but in 0/26 recovered from Covid without PASC (10 admitted to ICU).

 

Long covid has made the idea of persistent infection much more credible.

One argument against persistent infection in ME/CFS has been that as the health declines, one would expect the pathogens to eventually win and cause a rather obvious infection.

Maybe this is a stupid idea but: is it possible that infections don't persist indefinitively, but for a few years, and in this time, causes such a dsyregulation of the immune system that it's hard to recover from that?

Or maybe the human body is just able to suppress the pathogen (but not eradicate it) until the moment of death.

 

The hypothesis was always credible. We have known for a very long time that pathogens can persist inside the body and there are probably hundreds of ways they can interact with cells that we still don't know about. Given that we know pathogens can cause trouble it's not absurd to think one of these yet unfound interactions could in fact be ME/CFS, especially considering the similarities with symptoms.

The problem is that medicine is structured in a way such that doctors are taught to think they know everything about biology. So you grab a bunch of patients, do your standard infectious disease tests and if they are negative you conclude there are no infections and move on. It's not that easy. All you have proven is that the patients don't have a known infectious disease but you would already know that from the clinical picture.

 

I wonder if anyone has looked for antigens from the usual viral suspects in ME plasma.

Obviously there have been lots of antibody studies, but have any studies done what was done in this study, i.e. an assay for specific antigens from a suspect virus? For example, it might be interesting to see if some ME patients have elevated levels of EBV antigens relative to EBV-antibody positive healthy controls. Perhaps this could point to a specific virus in a specific group of patients where for whatever reason significant levels of circulating antibodies aren't found.

A quick search doesn't turn up any papers looking for antigens specifically.

 

Ariza et al from The Ohio State University have had a long standing NIH EBV grant and have published quite a bit on dUTPase's in ME/CFS. I'm quite surprised that the below thread had no comments or discussion given that it has a relatively large cohort.
https://www.s4me.info/threads/ebv-h...-activities-2022-cox-et-al.27394/#post-416943

Like Prusty et al have done for HHV6, Ariza et al have now confirmed that there does not need to be replicating EBV in order to generate viral proteins. She presented at a closed IACFS online meeting recently that I somehow was able to attend.

Edit to add another Ariza et al paper.
https://www.s4me.info/threads/epste...ications-for-me-cfs-2019-williams-et-al.9327/

 

I've seen a number of people wondering on Twitter why they found spike protein, but almost never S1, given that you'd expect S to be cleaved into S1 and S2.

 

this is probably a reply that has obvious answers from the paper or even op, but what is the half life of the protein in normals given the same methodology?

also, do we have any surmises at whether the protein itself is harmful rather than downstream of something? also, does the result say anything potentially useful about any disease population wrt v? e.g. worsening or improving.

 

Now published, open access, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac722/6686531

 

A response letter to the study

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac895/6831665

Download the pdf preview