Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19

Authors: Yang Yang, MD, Chenguang Shen, PhD, Jinxiu Li, MD, Jing Yuan, MD, Jinli Wei, MM, Fengmin Huang, MD, Fuxiang Wang, MD, Guobao Li, MD, Yanjie Li, MM, Li Xing, MM, Ling Peng, MM, Minghui Yang, PhD, Mengli Cao, MM, Haixia Zheng, MM, Weibo Wu, MM, Rongrong Zou, MD, Delin Li, PhD, Zhixiang Xu, MM, Haiyan Wang, PhD, Mingxia Zhang, MM, Zheng Zhang, MD, George F. Gao, DPhil, Chengyu Jiang, PhD, Lei Liu, MD, Yingxia Liu, MD 

Link to paper: https://doi.org/10.1016/j.jaci.2020.04.027

Journal/ Pre-Print: Journal of Allergy & Clinical Immunology

Tags: Diagnostics, Clinical, Immunology/Immunity

Research Highlights 

1. IP-10, MCP-3, HGF, MIG and MIP-1α levels are highly correlated with disease severity, with highest level in the critically ill patients followed by severe ones, and not elevated in moderately ill patients.

2. IP-10, MCP-3 could be a predictor for the progression of COVID-19

Summary

Samples from 50 patients with different disease severity were collected at different stages after hospitalisation for measuring cytokine levels. 14 out of 30 were significantly elevated in COVID 19 cases compared to healthy donors. IP-10, MCP-3, HGF, MIG and MIP-1α levels significantly? correlate with disease severity. High concentrations of IP-10 and MCP-3 were measured in critically and severely ill patients and might serve as a predictor for increased disease severity.

Impact for SARS-CoV2/COVID19 research efforts

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

Understand the immune response to SARS-CoV2/COVID19

Develop diagnostic tools for SARS-CoV2/COVID19

Treatment of SARS-CoV2/COVID19 positive individuals 

Study Type

- Patient Case study

Strengths and limitations of the paper

Novelty: Potential cytokine biomarker profile for different disease stages established

Standing in the field: Confirms cytokines that were previously described in association with cytokine storms in COVID-19 patients; IP-10 has also been shown to be associated with disease severity of H5N1, H1N1, SARS-CoV and MERS-CoV

Appropriate statistics: Yes

Viral model used: Confirmed cases of COVID-19-infected patients

Translatability: Correlated cytokines could serve as a disease progression biomarker in clinics

Main limitations:

- High rate of underlying health conditions in patients associated with high age (Diabetes/ Heart Conditions), did not mention if healthy controls were age-matched, underlying conditions might contribute to higher inflammatory cytokine levels

- Patients partly received anti-viral treatments/ other treatments which might influence the cytokine levels measured

- In vivo SARS-CoV2 infection model could be used to see if infection also increases above-mentioned cytokines in an animal model

- to test therapeutic potential & understand cytokine kinetics better, in vitro experiments blocking relevant cytokines are needed

- Is the sample number big enough?

· IL-1alpha & IL-1beta are upregulated in all severity stages compared to healthy controls, whereas IL-6 is not, this would be worth following up why these are upregulated