Immunological dysfunction persists for 8 months following initial mild-moderate SARS-CoV-2 infection, 2021, Phetsouphanh et al

Hoopoe

Hoopoe

Senior Member (Voting Rights)
Preprint

Abstract
A proportion of patients surviving acute COVID-19 infection develop post-COVID syndrome (long COVID) encompassing physical and neuropsychiatric symptoms lasting longer than 12 weeks. Here we studied a prospective cohort of individuals with long COVID (the ADAPT study) compared to age/gender matched subjects without long COVID, healthy donors and individuals infected with other non-SARS CoV2 human coronaviruses (the ADAPT-C study). We found an elevated diffuse serum inflammatory cytokine profile in symptomatic long COVID subjects that was maintained at 8 months post-infection and was not observed in asymptomatic COVID-19 survivors. This inflammatory profile consisted of 15 cytokines that positively correlated; revealing an apparent diffuse, potentially coordinated, low level up regulation of a spectrum of immune and inflammatory mediators. In addition, we found an absence of subsets of un-activated naїve T and B cells in peripheral blood of long COVID subjects, that did not reconstitute over time. In contrast, individual serum cytokines from the interferon I and III classes, T cell activation markers and plasma ACE2, while elevated in the serum of people previously infected with SARS-CoV-2 were not further elevated in subjects with long COVID symptoms. This work defines immunological parameters associated with long COVID and suggests future opportunities to prevention and treatment.

https://www.medrxiv.org/content/10.1101/2021.06.01.21257759v1

The missing T and B cell subsets

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"Our data does have some limitations. Firstly, although our long COVID ‘cases’ and controls were matched for two major characteristics (age and gender) it is possible that the differences observed reflect other key demographic or other factors between the groups. Secondly, although 7 of the 29 analytes were observed to be abnormally elevated, 22 of 29 were not (including key cytokines often implicated in chronic fatigue syndromes such as Pentraxin- 3(PTX3), TGF-β1, and IL-13)62,63. This suggests long COVID may be differentiated from other post viral fatigue syndromes, however, our results require validation in other cohorts of long COVID to ensure their replicability."

Those references are

62. Tomoda, A., et al. Cytokine production and modulation: comparison of patients with chronic fatigue syndrome and normal controls. Psychiatry Res 134, 101–104 (2005)
63. Montoya, J.G., et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci U S A 114, E7150–E7158 (2017).

which seems like it is a limited selection.
 
An Australian paper. Authors:
  1. Chansavath Phetsouphanh 1*&,
  2. David Darley 2*,
  3. Anette Howe 1,
  4. C. Mee Ling Munier 1,
  5. Sheila K Patel 3,
  6. Jenifer A Juno 4,
  7. Louise M Burrell 3,
  8. Stephen J Kent 4,5,
  9. Gregory J Dore 1,2,
  10. Anthony D Kelleher 1,2†& and
  11. Gail Matthews 1,2†&
  1. The Kirby institute, University of New South Wales, NSW 2033, Australia
  2. St Vincent’s Hospital, Darlinghurst, NSW 2010, Australia
  3. Department of Medicine, Austin Health, University of Melbourne, Victoria 3084, Australia
  4. Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Victoria 3000, Australia
  5. Melbourne Sexual health centre, Infectious Diseases Department, Alfred health, central Clinical School, Monash University, Melbourne, Victoria 3004, Australia
Worth noting that Professor Andrew Lloyd is the Head of the Viral Immunology Systems Program with the Kirby Institute at the University of New South Wales, which is where 6 of the 11 authors are based. Lloyd is a leading proponent of BPS thinking, especially as applied to ME/CFS. Given the subject of the paper, he will have certainly had an influence. So it's interesting to see the suggestion that Long Covid is something other than CFS coming from this group, as well as the ongoing efforts in cytokine measurements. Positioning Long Covid as different to CFS allows them to continue to easily maintain that GET and CBT fix CFS, while winning funding to investigate the biological basis of Long Covid.
Lloyd is also the head of the UNSW Fatigue Clinic and Research Program.

Austin Health has been on our radar as a hotbed of MUS thinking in Melbourne. 2 of the 11 authors are with Austin Health, although they may not be associated with the MUS part - I haven't looked.
 
Andy said:
"Our data does have some limitations. Firstly, although our long COVID ‘cases’ and controls were matched for two major characteristics (age and gender) it is possible that the differences observed reflect other key demographic or other factors between the groups. Secondly, although 7 of the 29 analytes were observed to be abnormally elevated, 22 of 29 were not (including key cytokines often implicated in chronic fatigue syndromes such as Pentraxin- 3(PTX3), TGF-β1, and IL-13)62,63. This suggests long COVID may be differentiated from other post viral fatigue syndromes, however, our results require validation in other cohorts of long COVID to ensure their replicability."

Those references are

62. Tomoda, A., et al. Cytokine production and modulation: comparison of patients with chronic fatigue syndrome and normal controls. Psychiatry Res 134, 101–104 (2005)
63. Montoya, J.G., et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci U S A 114, E7150–E7158 (2017).

which seems like it is a limited selection.
Click to expand...
I don't know if anyone here noticed but this part is actually missing from the now published version.
 
Dr Charles Shepherd's comment from the MEA website:

As the researchers correctly note, this finding of on-going immune system activation in Long Covid has also been reported in ME/CFS.

Linked to this very interesting overlap between Long Covid and ME/CFS is the involvement of immune system chemicals called cytokines – which cause inflammation and many of the symptoms associated with any acute infection.

During the acute stage of COVID-19 there can be what is termed a cytokine storm – with a massive overproduction of cytokines causing inflammation in the lungs and serious respiratory complications. There is also research evidence in ME/CFS to indicate that an on-going cytokine response involving what are called pro-inflammatory cytokines fails to ‘switch off’ after the initial triggering infection.

Cytokines can then pass through what is called the blood-brain barrier and affect an area of the brain called the hypothalamus (which acts as a thermostat for temperature control along with appetite, sleep and hormone regulation) and control centres in the brain for the autonomic nervous system (which controls heart rate and blood pressure and leads to orthostatic intolerance and PoTS).

However, I think it’s important to note that Long Covid is an umbrella term that covers a wide range of on-going health problems that occur after COVID-19 infection and there are also likely to be a number of causative mechanisms involved – not just on-going low level immune system activation.
Click to expand...

(Though I couldn't find where the authors noted the similarity with ME/CFS. Maybe it was in a different article I haven't come across.)
 
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