Isabelle Cremer’s team and colleagues propose using the SARS-Score to assess the risk of worsening in COVID19 patients. Published in Frontiers in Immunology on July 12, 2021.
A collaborative team led by Isabelle Cremer at the Cordelier Research Center has shown that a set of easily analyzed immune system biomarkers can identify patients at high risk of developing a severe form of the disease. Based on these markers, the researchers propose to assign an “SARS-Score” to patients upon their arrival at the hospital in order to adapt the treatment to their immune profile. These findings are published in Frontiers in Immunology on July 12, 2021.
Coronavirus 2019 (COVID-19) disease, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has affected more than 118 million people and is responsible for 2.6 million deaths since the start of the pandemic (WHO data 11 March 2021). The clinical course of patients infected with SARS-CoV-2 is highly variable among individuals, ranging from asymptomatic for the majority of patients to severe symptoms. Ten to 20% of patients require hospitalization and admission to an intensive care unit, primarily due to acute respiratory distress syndrome or multi-organ failure. Certain factors increase the risk of COVID-19 severity, including advanced age, male gender, and cardiovascular comorbidities-diabetes, obesity, and hypertension.
The therapeutic management of hospitalized patients is a major problem and the identification of immune biomarkers that could predict the clinical course of patients could greatly improve their management.
In this context, the researchers performed an in-depth analysis of different elements of the immune system on a cohort of hospitalized patients with COVID-19. They analyzed for each patient the proportions of the different cell types of the immune system by flow cytometry, the profiles of expressed genes (transcriptomic data) as well as numerous clinical parameters reflecting organ damage: WHO score for respiratory function, urinary sodium and potassium for renal function, index of hepatic steatosis and prothrombin level for liver functions, troponin for cardiac function and E-selectin for blood vessel status, among others.
They were thus able to identify two groups of patients who differ in the expression of immune genes and differ in the level of disease severity. Thus, genes highly expressed in patients with severe disease reflect a signature of myeloid and neutrophilic cells, a strong inflammatory response and genes under-expressed show a diminished adaptive immune response (decreased antigen presentation, proliferation and activation of T cells).
In parallel, the researchers identified a set of easily quantifiable biomarkers, called the “SARS-Score”, which can identify patients at high risk of developing a severe form of the disease. This score includes 7 genes: CEACAM1, S100A8, S100A12, CSF1R, TLR5, CD59 and CD96, whose expression distinguishes patients, as well as a combination of 8 clinical variables: BMI (body mass index), WHO score, heme oxygenase 1, urinary sodium, E-selectin, prothrombin level, troponin and lymphocyte count.
Based on these results, the researchers searched databases of therapeutic molecules to identify drugs that could act on the different parameters they found associated with the development of severe forms. This analysis allowed to identify several molecules that could be used to avoid the aggravation of patients, including glucocorticoids, anti-inflammatory drugs, immunosuppressants, or immunoregulatory molecules. Some of these molecules are in fact already being tested in clinical trials.
This study provides physicians with an important diagnostic tool, the SARS-Score, as well as several therapeutic avenues to avoid the development of severe forms of COVID19 disease.
Reference: Immune Signature Linked to COVID-19 Severity: A SARS-Score for Personalized Medicine, Russick et al.Front. Immunol, 12 July 2021.