关键词： 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)

来  源：   DOI：10.1016/j.jtauto.2021.100083   PDF(Sci-hub)   PDF(Pubmed)

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.
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