Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab.
ACE2, angiotensin-converting enzyme 2
ALT, alanine aminotransferase
ARDS, acute respiratory distress syndrome
AST, aspartate aminotransferase
Acute respiratory distress syndrome (ARDS)
BID, bis in die (twice a day)
CCL2, chemokine C–C motif ligand 2
CCL3, chemokine C–C motif ligand 3
CCL4, chemokine C–C motif ligand 4
CCL5, chemokine C–C motif ligand 5
CCR1, C–C chemokine receptor type 1
CCR5, C–C chemokine receptor type 5
CDC, Centers for Disease Control
CK, creatine kinase
COPD, chronic obstructive pulmonary disease
COVID-19, coronavirus disease 2019
CRP, C-reactive protein
CXCL10, chemokine C-X-C motif ligand 10
CXCL2, chemokine C-X-C motif ligand 2
Coronavirus disease 2019 (COVID-19)
DPP4, dipeptidyl peptidase-4
DVT, deep vein thrombosis
EDTA, ethylenediaminetetraacetic acid
FDA, Food and Drug Administration
Fi02, fraction of inspired oxygen, IgG4
Hydroxychloroquine, HLH
Leronlimab (PRO 140)
Middle East respiratory syndrome coronavirus, MIG
National Early Warning Score, NK
RO, receptor occupancy
RT–PCR, reverse transcriptase polymerase chain reaction
SARS-CoV, severe acute respiratory syndrome coronavirus
SARS-CoV-2
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
T-reg RO, regulatory T cells – receptor occupancy
TGF- α, transforming growth factor alpha
TNF-α, tumor necrosis factor alpha
TNF-β, tumor necrosis factor beta
Tregs, regulatory T cells
VEGF-A, vascular endothelial growth factor A
WBC, white blood cell
WHO, World Health Organization
eIND, emergency investigational new drug application
hemophagocytic lymphohistiocytosis, HTN
hypertension, ICU
immunoglobulin G4, HCQ
intensive care unit, IL-1β
interferon gamma, IL-6
interferon gamma-inducible protein (IP) 10 or CXCL10, LOA
interleukin 1 beta, IFN-ƴ
interleukin 6, IP-10
letter of authorization, MCP
macrophage Inflammatory Proteins 1-alpha, MIP-1β
macrophage Inflammatory Proteins 1-beta, N/A
macrophage colony stimulating factor, MDC (CCL22)
macrophage colony-stimulating factor encoded by the CCL22 gene, MERS-CoV
monocyte chemoattractant protein, M-CSF
monokine induced by IFN-γ (interferon gamma), MIP-1α
natural killer, OSA
not applicable, NEWS2
obstructive sleep apnea, PDGF-AA
per os (taken by mouth), RANTES
platelet-derived growth factor AA, PDGF-AA/BB
platelet-derived growth factor AA/BB, PEEP
positive end-expiratory pressure, PNA
pulmonary nodular amyloidosis, po
regulated on activation, normal T expressed and secreted (also known as CCL5)
Journal
Journal of translational autoimmunity
ISSN: 2589-9090
Titre abrégé: J Transl Autoimmun
Pays: Netherlands
ID NLM: 101759413
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
09
2020
revised:
25
12
2020
accepted:
30
12
2020
entrez:
1
2
2021
pubmed:
2
2
2021
medline:
2
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33521616
doi: 10.1016/j.jtauto.2021.100083
pii: S2589-9090(21)00003-4
pmc: PMC7823045
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
100083Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Dr. Kelly is the chief medical officer of Cytodyn and Dr Pourhassan is the chief executive oficer of Cytodyn and have a financial interest in Cytodyn but did not influence the work reported in this paper. Dr. Dhody is the Chief research officer for Amarex and may have a financial interest in Cytodyn but did not influence the work reported in this paper. Dr Sacha is a consultant for Cytodyn but did not influence the work reported in this paper.
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