Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab

Nicholas Agresti, Jacob P. Lalezari, Phillip P. Amodeo, Kabir Mody, Steven F. Mosher, Harish Seethamraju, Scott A. Kelly, Nader Z. Pourhassan, C. David Sudduth, Christopher Bovinet, Ahmed E. ElSharkawi, Bruce K. Patterson, Reejis Stephen, Jonah B. Sacha, Helen L. Wu, Seth A. Gross, Kush Dhody

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C–C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0–7 and patient D (p=0.027) from day 0–14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection.

Original languageEnglish (US)
Article number100083
JournalJournal of Translational Autoimmunity
Volume4
DOIs
StatePublished - Jan 2021

Keywords

  • Acute respiratory distress syndrome (ARDS)
  • Coronavirus disease 2019 (COVID-19)
  • Leronlimab (PRO 140)
  • SARS-CoV-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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