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. Highlights • Leronlimab is a monoclonal antibody in clinical trials to treat the cytokine storm. • Critically ill patients received leronlimab through compassionate use and had remarkable recoveries measured objectively. • The CCR5 receptor is important in recruiting inflammatory cells mainly T cells and macrophages. • Leronlimab disrupted this signal and may have been responsible for restoration of the immune system, improved survival and decrease in IL-6.
【저자키워드】 SARS-CoV-2, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, ACE2, angiotensin-converting enzyme 2, Coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), COPD, Chronic obstructive pulmonary disease, SARS-CoV, severe acute respiratory syndrome coronavirus, ARDS, acute respiratory distress syndrome, WHO, World Health Organization, CRP, C-reactive protein, WBC, White blood cell, FDA, Food and Drug Administration, Leronlimab (PRO 140), ALT, alanine aminotransferase, AST, aspartate aminotransferase, 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, CXCL2, chemokine C-X-C motif ligand 2, CXCL10, chemokine C-X-C motif ligand 10, DPP4, dipeptidyl peptidase-4, DVT, deep vein thrombosis, EDTA, ethylenediaminetetraacetic acid, eIND, emergency investigational new drug application, Fi02, fraction of inspired oxygen, IgG4, immunoglobulin G4, HCQ, Hydroxychloroquine, HLH, hemophagocytic lymphohistiocytosis, HTN, hypertension, ICU, intensive care unit, IL-1β, interleukin 1 beta, IFN-ƴ, interferon gamma, IL-6, interleukin 6, IP-10, interferon gamma-inducible protein (IP) 10 or CXCL10, LOA, letter of authorization, MCP, monocyte chemoattractant protein, M-CSF, macrophage colony stimulating factor, MDC (CCL22), macrophage colony-stimulating factor encoded by the CCL22 gene, MERS-CoV, Middle East respiratory syndrome coronavirus, MIG, monokine induced by IFN-γ (interferon gamma), MIP-1α, macrophage Inflammatory Proteins 1-alpha, MIP-1β, macrophage Inflammatory Proteins 1-beta, N/A, not applicable, NEWS2, National Early Warning Score, NK, natural killer, OSA, obstructive sleep apnea, PDGF-AA, platelet-derived growth factor AA, PDGF-AA/BB, platelet-derived growth factor AA/BB, PEEP, positive end-expiratory pressure, PNA, pulmonary nodular amyloidosis, po, per os (taken by mouth), RANTES, regulated on activation, normal T expressed and secreted (also known as CCL5), RO, receptor occupancy, RT–PCR, reverse transcriptase polymerase chain reaction, TGF- α, transforming growth factor alpha, TNF-α, tumor necrosis factor alpha, TNF-β, tumor necrosis factor beta, Tregs, regulatory T cells, T-reg RO, regulatory T cells – receptor occupancy, VEGF-A, vascular endothelial growth factor A, 【초록키워드】 COVID-19, Treatment, Coronavirus disease 2019, clinical trial, macrophages, intensive care, severe COVID-19, mechanical ventilation, IL-6, SARS-COV-2 infection, monoclonal antibody, surgical, immune system, virus, chemokine, T cell, survival, Hemodialysis, Critically ill, Host immune response, Patient, Complication, immune function, plasma, morbidity and mortality, receptor, Chemokine receptor, CCR5, compassionate use, Ligand, administration, deaths, COVID-19 patient, immune dysregulation, IgG4, inflammatory cell, Critically ill patient, confirmed case, treat, CCL5, pathogenic, CD4/CD8, vasopressor support, Administered, block, end-organ damage, humanized, effective, decrease, initial, thought, shown, responsible, died, the patient, clinically, elevated, reduce, dysregulated, statistically significant, infection with SARS-CoV-2, normalized, the cytokine storm, 【제목키워드】 cytokine, CCR5, Signaling, Disruption, Critically ill patient, treat, treated,