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Study indicates testing COVID-19 patients for particular proteins could help predict later disease severity

A recent research paper published in the BSI's official journal Clinical & Experimental Immunology suggests testing the blood of hospitalised COVID-19 patients for particular proteins, could help predict if they will become critically ill with the disease.

White blood cellsThe study, carried out by a group from the Department of Laboratory Medicine at Huazhong University of Science and Technology in Wuhan, China, involved 389 patients hospitalised with COVID-19 over a 3-week period in early 2020. The patients were divided into three groups according to the severity of their symptoms; mild (168 patients), severe (169 patients) and critical (52 patients). The scientists confirmed they were all suffering with COVID-19 via a nose or throat swab test and then carried  out a number of blood tests for all patients to compare their levels of a number of ‘biomarkers’. Their aim was to identify any associations between the results of such tests, and the disease severity and outcome for COVID-19 patients, to help find efficient ways to predict how ill someone is likely to get with this virus.

What are biomarkers?

Biomarkers are measurable indicators of the presence or severity of a disease or infection in the body. In the past, biomarkers were primarily physiological indicators such as blood pressure or heart rate. Today many biomarkers are molecular – for example levels of particular proteins in the blood or other body fluids (e.g. antibodies and enzymes) are analysed by hospital laboratories to investigate a particular symptom or illness. Measuring the number of white blood cells is also a way to test for an infection. White blood cells protect the body against infection and are critical to the immune response.

What tests were carried out in this study and why?

The study at Huazhong University tested the patients’ blood for numbers of white blood cells, and for three other biomarkers that are used routinely when monitoring patients in hospital. In addition the scientists also tested levels of proteins called cytokines. Cytokines are produced by the body in response to inflammation and distress. Six different cytokine ‘profiles’ were taken for all patients in the study because an earlier study indicated higher levels of these proteins in critically ill COVID-19 patients, who had already been admitted to intensive care. The scientists in this follow-up study therefore wanted to investigate if these biomarkers could be used as a way of identifying severe COVID-19 earlier. The selected biomarkers were measured when the patients were admitted to hospital or when their disease progressed. Samples were also taken from those who recovered prior to discharge.

What did the results of this study show?

The scientists compared the biomarker results between the three groups of COVID-19 patients and found all of the six cytokine proteins, and a number of other biomarkers were increased with increasing severity of illness. One biomarker that did not follow this pattern was a type of white blood cell called a lymphocyte, which play an important role in protecting the body against infections. Lymphocyte levels were significantly lower in patients who were more critically ill with COVID-19. The scientists also found a particularly marked difference between patient groups in terms of the ratio between levels of a protein called IL-2R and lymphocytes i.e. patients with both high IL-2R levels and low lymphocyte levels were particularly susceptible to severe disease. Differences in ratios between other biomarkers were found between the three patient groups but the IL-2R:lymphocyte differences were the most significant. This measure was found to decrease in COVID-19 patients who recovered during the study, whereas it remained high in those whose condition deteriorated further over the same time period.

What can we conclude from this study?

This study builds on our understanding of how the immune response in COVID-19 patients affects the severity of their illness. The finding that the ratio between IL-2R levels and lymphocyte count differed significantly between patient groups suggests this measure may be useful to identify COVID-19 patients with severe disease early and may be a possible biomarker to help predict how those patients’ symptoms may develop. However it is important to recognise this was an individual study using a fairly small sample of patients. Independent validation and in-depth research into the IL-2R:lymphocyte ratio (and other biomarker levels), in larger groups of patients, is needed, before any changes to clinical practices can be made.

Hou, H., Zhang, B., Huang, H., Luo, Y., Wu, S., Tang, G., Liu, W., Mao, L., Mao, L., Wang, F., Sun, Z. (2020) Using IL‐2R/lymphocytes for predicting the clinical progression of patients with COVID‐19. Clinical & Experimental Immunology. doi:10.1111/cei.13450

Accepted for publication 28 April 2020

First published 4 May 2020

Summary author Penny Fletcher