News Release 

COVID-19: Biomarkers linked to severe forms of the disease

University of Montreal Hospital Research Centre (CRCHUM)

Research News

A team of researchers from the CHUM Research Centre has identified new biomarkers associated with the severity of COVID-19 in infected patients.

Recent scientific literature has shown that the immune response plays a central part in the severity of COVID-19 disease. Understanding the immune responses generated during the course of the disease is therefore essential to determine which patients are at highest risk for serious complications and death from the disease.

In a new study published in the Journal of Clinical Investigation, scientists and clinicians led by Dr.?Catherine Larochelle, researcher at the CHUM Research Centre, have shown that a set of immune alterations are specifically linked to infection with the SARS-CoV-2 virus, as well as to the severity of COVID-19 disease, its 30-day evolution, and its 60-day mortality. These biomarkers could represent potential therapeutic targets.

We have discussed this with Dr. Larochelle, Professor at the Université de Montréal (Department of Neuroscience) and principal author of the study.

Q. Your experimental approach is rather unique. Based on the immune profiling you conducted, how were you able to identify the patients most at risk for a poor prognosis?

Above all, this is the result of a tremendous collective effort by several dozen people involved in research and clinical work at the CHUM, who participated in this study and in the Quebec?COVID-19 (BQC19) Biobank.

Based on a blood test, we were able to inventory the immune cell populations present in 50 patients with SARS-CoV-2 and compare them to those of 22 patients (of similar gender and age) hospitalized for other acute illnesses, and those of 49 healthy controls.

This immune profiling allowed us to identify subsets of "dysregulated" immune cells specific to patients affected by SARS-CoV-2. Most notably, some of these immune alterations were associated with ventilation needs and mortality in these same patients.

These markers specific to SARS-CoV-2 could then help us to identify the patients at greatest risk, and suggest new avenues for developing therapeutic targets.

In addition, we confirm what has been observed in other studies: disturbances in the immune system such as neutrophilia or lymphopenia, for example, are related to the severity of the disease in hospitalized patients, but are not specific to SARS-CoV-2.

From a clinical perspective, this could explain why general anti-inflammatory treatments such as steroids seem to work in COVID-19 and other acute diseases.

Q. How do you see your results being used directly in a clinical setting? Is it technically feasible?

These assays could be easily transferred to clinical settings, because we worked with very small amounts of blood--less than one millilitre--to develop these immune profiles.

In our experimental approach, we used techniques commonly employed in hospital laboratories: use of surface antibodies to "stain" the cells that express certain markers, flow cytometry (cell characterization and counts), etc. In a clinical setting, this could help track the progress of patients over time and ultimately identify those at high risk who would require closer monitoring.

Q. What therapeutic horizons do you envision for your research work?

I hope that our study will lead to the development of biomarkers that will help us stratify patients based on their risk of developing a severe form of the disease. This should also allow us to identify new therapeutic targets, and to better select those patients who might benefit from certain available therapeutic approaches.

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About the study

The article "Identification of SARS-CoV-2-specific immune alterations in acutely ill patients" by Rose-Marie Rébillard et al., was published Feb. 26, 2021 in the Journal of Clinical Investigation.

Funding for the study was provided by the Fondation du CHUM, the Working Group on Immunity to COVID-19, and the Canadian Institutes of Health Research. BQC19 is an initiative funded by the Fonds de recherche du Québec-Santé, Génome Québec, and the Public Health Agency of Canada in order to better understand the evolution and the determinants of the SARS-CoV-2 infection.

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