Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome, Gaylis et al (2022)

SNT Gatchaman

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Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome
Norman B Gaylis, Angela Ritter, Scott A Kelly, Nader Z Pourhassan, Meenakshi Tiwary, Jonah B Sacha, Scott G Hansen, Christopher Recknor, Otto O Yang

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In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab.
 

SNT Gatchaman

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They took 55 Long Covid patients and gave half this MAb, which is an IgG4 that binds to CCR5.

Background
CCR5 is a G protein-coupled receptor (GPCR) for its chemokine (chemotactic cytokine): CCL5. CC is a subgroup of such chemokines, which are labelled (a little confusingly) according to their structure. "CC" here doesn't mean "chemotactic cytokine" but refers to the position of cysteine residues - two adjacent in this case. See the wikipedia diagram here.

CCL5 is the ligand, CCR5 is the cell surface receptor. CCL5 is aka "RANTES" (a backronym for "regulated on activation, normal T cell expressed and secreted").

Findings
  • Placebo had no effect on CCR5 expression, as expected.

  • In the treatment arm, some had a symptomatic response. All of those symptomatic responders showed an upregulation of CCR5 expression (p < 0.0001, though small numbers of course).

  • From no difference between treatment and placebo arms at baseline, there were also changes at 56 days in "key adaptive immune cell populations" (I think Treg's in particular, but can't access the supplementary data currently).
 
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Pyrrhus

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In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders
That is indeed surprising. It looks like they used monoclonal antibodies designed as an immune-suppressant, but found an immune-boosting effect instead. Clarification will definitely be needed here.

I wonder if they would see the same effect with maraviroc?


Possibly related conversation:

What is the impact on COVID from a deletion mutation in the CCR5 gene?
https://forums.phoenixrising.me/thr...via-23andme-results.28913/page-2#post-2322593