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Authors: Da-Zhi Guo et al.

Link to paper: https://www.researchsquare.com/article/rs-19182/v1

Journal/ Pre-Print: In review at BMC Infectious Diseases, posted to Research Square (1st Apr 2020)

Key Words: Circulating microparticles, IL-6, IL-8, IL-10, cytokine storm

Research Highlights 

1. Circulating microparticles are significantly elevated in COVID-19 patients compared to healthy controls and correlate with disease severity.

2. IL-6, IL-8, and IL-10 are significantly elevated in COVID-19 patients compared to healthy controls and correlate with disease severity.

3. Older patients and patients with history of coronary heart disease present with more severe disease.

Summary

In this paper levels of pro-inflammatory cytokines and circulating microparticles (cMP, a type of large extracellular vesicles) in blood of COVID-19 patients with varied disease severity were analysed and compared to healthy control individuals. Levels of cMP, IL-6, IL-8 and IL-10 were increased in patients compared to healthy controls, and positively correlated with disease severity. In conclusion, cMP, IL-6, IL-8 and IL-10 could be used to predict disease severity and are prospective therapeutic targets.

· Does the paper increase our understanding of COVID19?

To a limited extent, the paper mostly corroborates previous studies on increased levels of pro-inflammatory cytokines in COVID-19 patients.

· How does the study add to current knowledge?

The study shows previously unreported increase of circulating microparticles in COVID-19 patients, albeit the significance or the source of circulating microparticles remains unknown

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Pro-inflammatory cytokines (IL-6, IL-8 and IL-10) and circulating microparticles are increased in COVID-19 patients.

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

Disease severity correlates with levels of pro-inflammatory cytokines (IL-6, IL-8 and IL-10) and circulating microparticles.

Treat of SARS-CoV2/COVID19 positive individuals

Inhibition of cMP shedding and expression of IL-6, IL-8 and IL-10 could be valuable for preventing the progression of COVID-19, but substantial further work will be required.

Study Type

· Patient Case study (case-control study, 89 COVID-19 patients and 30 healthy control individuals)

Strengths and limitations of the paper

Novelty: Circulating microparticles are elevated in COVID-19 patients.

Standing in the field: Not controversial. Microparticle shedding have been previously associated with infectious diseases (sepsis, HIV infection, flavivirus encephalitis, malaria). Cytokine storm has been previously reported in COVID-19 patients.

Appropriate statistics: Yes

Viral model used: SARS-CoV-2

Translatability: Pro-inflammatory cytokines and microparticles can have clinical value as disease severity markers.

Main limitations: Patients in the different disease severity groups differ in age and white blood cell counts – this can affect measured parameters. No follow up data is shown. Overall little added value to existing understanding of the disease, purely observational study, no mechanistic data presented.