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

rvallee

rvallee

Senior Member (Voting Rights)
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.

Paywalled: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciac226/6572226
 
Erm....People whose cells produced a response had more of a that response than those that didn't?

The quoted bit seems devoid of meaning.
 
Leronlimab and the pharmaceutical company CytoDyn who investigates it don't really have a good reputation:

CytoDyn Hit with Two Clinical Holds as Optimism Appears to Wane

"In May 2021, the FDA issued an unusual public scolding of the company, accusing it of misrepresenting clinical trial data of leronlimab for COVID-19. The statement focused on data from two clinical trials, CD10, in 86 mild-to-moderate COVID-19 patients, and CD12, in 394 patients with severe symptoms. "​

They apparently had a run-in with our "beloved" Bruce Patterson too (of IncellDx):

"In August 2021, the company was battling against an activist investor group led by Paul Rosenbaum and Bruce Patterson. CytoDyn filed a lawsuit against the group, alleging they were misleading shareholders and “waging an illegal proxy contest to take over control of the Company’s Board of Directors.”"​

Or another article about the same thing: After an RTF and some stern warnings, FDA slaps CytoDyn with two clinical holds

"Under former CEO Nader Pourhassan, CytoDyn became known for its aggressive — bordering on the reckless — promotional campaigns, pumping press release after press release to tout the (unsubstantiated) potential of leronlimab as a Covid-19 treatment. At the same time, Pourhassan went on webcasts and recorded videos to talk up the drug, undeterred even after the FDA rejected a BLA for its use in HIV, its original indication, and the drug failed a pair of Covid-19 studies."
​
So this story so far looks a bit like a pharmaceutical telenovela to me.
​
 
Yes.. CytoDyn is very controversial. Adam Feuerstein who reports for Stat News often tweets and writes about them.



 
To clarify: the interest I see is mostly about the immune downregulation it implies and the CCR5 receptor, rather than the drug. But this is above my tiny understanding of biology.
 
The CCR5 difference that they find only falls out of the post-hoc responder versus non-responder analysis though, so there isn't anything there if you're not willing to buy that the drug is doing something.
 
Not all the relevant cohort details are currently available (I think the article is being added to, hopefully to include this data).

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

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").

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).

The suggestion then being made is that CCR5 has a role in Long Covid and this can be modified in association with symptoms improvement in some patients via this MAb. Note that Maraviroc, as championed by Bruce Patterson, is a CCR5 antagonist (discussed in threads here and here).
 
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