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Clinical Trial
. 2022 Sep 30;75(7):1232-1234.
doi: 10.1093/cid/ciac226.

Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome

Norman B Gaylis  1 , Angela Ritter  2 , Scott A Kelly  3 , Nader Z Pourhassan  3 , Meenakshi Tiwary  4 , Jonah B Sacha  4 , Scott G Hansen  4 , Christopher Recknor  3 , Otto O Yang  5   6
Affiliations
Clinical Trial

Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome

Norman B Gaylis et al. Clin Infect Dis. .

Abstract

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. Clinical Trials Registration. NCT04678830.

Keywords: CCR5; immunosuppression; leronlimab; long COVID.

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Conflict of interest statement

Potential conflicts of interest. S. A. K., N. Z. P., and C. R. are officers of CytoDyn Inc and report stock options and consulting fees from CytoDyn, assistance with manuscript preparation (Medical Expressions, paid by CytoDyn), and other financial or nonfinancial interests as employees of CytoDyn. J. B. S., S. G. H., and O. O. Y. are paid consultants for CytoDyn Inc. J. B. S. reports stock options available for purchase from CytoDyn and assistance with manuscript preparation (Medical Expressions, paid by CytoDyn). S. G. H. reports stock options and receipt of leronlimab for CCR5 receptor occupancy assay from CytoDyn and assistance with manuscript preparation (Medical Expression, paid by CytoDyn). O. O. Y. reports assistance in writing the manuscript (paid by CytoDyn). M. T. reports assistance with manuscript preparation (Medical Expressions, paid by CytoDyn). N. B. G. was a principal investigator for this trial, serves on the CytoDyn Inc Scientific Advisory Board with stock options, and reports assistance with manuscript preparation (Medical Expressions, paid by CytoDyn). A. R. was a principal investigator for this trial and worked as an employee at the Center for Advanced Research & Education, Gainesville, Georgia, which is performing a clinical research trial for CytoDyn. A. R. reports assistance with manuscript preparation (Medical Expressions, paid by CytoDyn). All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Percentage CCR5 levels (CD45+/CCR5+) among participants treated with leronlimab or placebo. A, Percentage CCR5 expressing cells in the overall leronlimab (n = 26) and placebo (n = 28) groups. B, Percentage CCR5 expressing cells among participants in the leronlimab and placebo groups according to participants with and without improving long coronavirus disease 2019 symptoms (14/12 and 10/18 were improved/unimproved for the leronlimab and placebo groups, respectively). The median (50th percentile; center horizontal line), interquartile range (the 25th to the 75th percentile; box), and “whiskers” (whiskers are the 0th percentile and the 100th percentile) are indicated. One data point greater than 20% (actual value of 28%) is depicted by * on the graph, but this value was included in all statistical analyses. Abbreviations: CCR5, C-C chemokine receptor 5; NS, not statistically significantly different.
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References

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