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Authors: B. Pattterson et al.

Link to paper: https://www.researchsquare.com/article/rs-26517/v1

Journal/ Pre-Print: Research Square

Tags: Immunology/Immunity, Bioinformatics, Drug repurposing, Therapeutics, Clinical/ Diagnostics

Research Highlights 

1. Disrupting the CCL5-CCR5 axis by CCR5 blocking antibody (leronlimab) treatment may reduce serum IL-6, increase the CD8/CD4 ratio and reduce viremia levels in critical COVID-19 patients.

2. Single-cell RNAseq on 2 critically ill patients before and after leronlimab treatment revealed a reduction of IL-6, chemokine and IFN-related gene transcripts in myeloid cells.

3. Compared to healthy controls, COVID-19 patients had higher serum IL-1b, IL-6, IL-8 and CCL5. Moreover, IL-6 and CCL5 levels correlated with severity.

Summary 

In this pilot study, 10 critically ill COVID-19 patients (6/10 renal transplant recipients) were given compassionate emergency use of Leronlimab, a CCR5-blocking antibody. The authors show a stepwise increase in serum concentrations of CCL5 (RANTES) from healthy controls, mild/moderate and critical patients. A single subcutaneous dose of Leronlimab bound to CCR5 on T cells and monocytes with high efficiency for over 14 days. The patients demonstrated a reduction in their plasma IL-6 level, a higher frequency of circulating CD8+ T cells and lower plasma viremia over 14 days. However, the lack of a control patient population and clinical outcomes prevents conclusions concerning efficacy.

Impact for SARS-CoV2/COVID19 research efforts

Postulates Leronlimab as a potential treatment of COVID-19 patients.

Study Type

· In silico study / bioinformatics study

· Clinical Cohort study (e.g. drug trials) – Pilot study

Strengths and limitations of the paper

Novelty: Introduction of Leronlimab as COVID-19 treatment. Controlled clinical trials necessary and ongoing.

Standing in the field: [How does this study compare to existing knowledge]

Appropriate statistics: No control or alternative treatments used in this study therefore it is not clear if there is any efficacy. Too small number of patients included in the study. Non-parametric statistical tests used.

Viral model used: SARS-CoV-2 infected patients (New York City, USA) in critical care.

Translatability: Yes. Randomised, double blind, controlled trials have been registered to test Leronlimab in mild, moderate, severe and critical patients to test the efficacy.

Main limitations:

- Limited number of patients and no control patient population included; therefore drug efficacy cannot be assessed.

- Needs inclusion of patient clinical outcomes.

- No information on the protein expression/functional status of CD8+ T cells/myeloid cells, or the therapeutic impact on humoral immunity.

- Would benefit from more information about patient recruitment (time from onset, time spent in ICU before recruitment, dates of recruitment).

- Needs inclusion of the criteria classifying mild, moderate and severe cases. Inclusion of information about mild/moderate patients (e.g. time from onset). Also needs a comment on the collection and virus status of the healthy control blood.