Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Authors: Shiyu Li et al.

Link to paper:

Journal/ Pre-Print: Research square

Tags: Immunology/Immunity, T cell responses, Bioinformatics, Therapeutics

Research Highlights 

1. In vitro stimulation of PBMCs of recovered COVID-19 patients with S protein + vMIP-II treatment increased the ratio central memory CD8 T cells (TCM): effector memory CD8 T cells (TEM) within the total memory CD8 T cell pool.

2. Gene expression profiling of untreated versus vMIP-II treated CD8 T cells by RNASeq indicated vMIP-II changes the expression of genes encoding for chemokine receptors and protein phosphorylation pathways. This was validated by qRT-PCR and few in vitro experiments, which include evidence of lower expression of a G protein α subunit, and decreased phosphorylation of MAPK/ERK and Akt.

3. vMIP-II treatment seems to increase the mitochondrial potential of CD8 T cells compared to non-treated cells.


The paper describes the potential benefit of treating COVID-19 patients with the chemokine inhibitor vMIP-II by ameliorating their reported lymphopenia/lymphocyte overreaction. A limited clinical trial showed that vMIP-II treatment helps recovery of lung lesions. Further experiments were mostly done by in vitro stimulation of PBMCs with recombinant SARS-COV2 S protein in the presence or not of vMIP-II treatment. The authors claim that vMIP-II treatment favours the differentiation of effector memory CD8 T cells into a central memory phenotype, but don’t investigate how de-differentiation might occur. In addition, the decreased frequencies of exhausted cells (PD1+TIM3+) found after vMIP-II treatment might suggest weak activation rather than apoptosis or higher proliferation ability. Transcriptional profiling of vMIP-II treated cells showed downregulation of genes linked to chemokine signalling and phosphorylation pathways, which was at least partially validated by qRT-PCR and in vitro assays. Overall this paper critically lacks evidence to conclude whether vMIP-II has therapeutic potential and its mechanism of action.

Impact for SARS-CoV2/COVID19 research efforts

Possible new therapy for SARS-CoV2/COVID-19 patients

Study Type

· In silico study / bioinformatics study

· In vitro study

· Clinical Cohort study – not a cohort but very limited number of patients

Strengths and limitations of the paper

Novelty: Potential use of a broad-spectrum chemokine receptor inhibitor (vMIP-II) to treat COVID-19 patients.

Standing in the field: Limited previous data on this topic

Appropriate statistics: Not detailed sufficiently. Sample size too small and no account is taken of multiple groups. No technical replicates. 

Viral model used: recombinant SARS-Cov2 S protein (S1 and S2 subunits) and COVID-19 patients from Wuhan.

Translatability: To test the efficacy of this drug (chemokine receptor inhibitor) it would require a better study design with control group and much larger cohort.

Main limitations:

- Just non-severe cases (10) and asymptomatic people (5) participated in the clinical trial. From the symptomatic patients, 5 received vMIP-II. No data is presented concerning their viral load.

- The treatment seems to enhance lung recovery in 5 patients, however as mild COVID-19 patients can have spontaneous recovery, it would be important to also present the CT images from the symptomatic untreated group, which was not done.

- Methods choice and study design were not well described for every experiment. Abbreviations are not explained, and how T cell subsets or cytokine production were assessed is not clear.

- Results are mostly limited to in vitro stimulated T cells (with recombinant S protein with/without vMIP-II).

- One of the major claims of the paper is that vMIP-II treatment benefits formation of central memory CD8 T cells, however just representative flow cytometry plots are shown, and no quantification can be found (for both frequencies and numbers of T cell subsets).

- They only looked at CD8 T cell memory phenotype after in vitro stimulation rather than directly from COVID-19 patient samples.

- Overall, the paper makes strong statements and claims causation effects without even strong supportive evidences of correlation between different results.