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Study of immune response in COVID-19 patients points to key indicators of disease severity

A recent research paper published in the BSI's journal Immunology has shown measuring certain blood cells and proteins involved in the immune response could be used as indicators of severe cases of COVID-19.

The study, carried out by a group from the Guangzhou Eighth People’s Hospital in the Chinese province Guangdong, investigated the immune responses of 56 patients diagnosed with COVID-19 symptoms. Twenty-five of the patients were classified as having ‘severe’ symptoms, and 31 were classified as having ‘mild’ symptoms (according to the classification guidelines issued by the National Health Committee of the People's Republic of China). Patients with a fever but negative for COVID-19 were included in the study as a ‘control group’ to compare against.

The researchers carried out blood tests on the patients before they were given any treatments to measure levels of particular cell types and proteins. They did this to build on understanding of how the immune system responds to COVID-19 infection, and how this plays a role in disease severity.  

What tests were carried out on the patients’ blood?

The study in Guangdong Province analysed the COVID-19 patients’ blood for levels of white blood cells including neutrophils and ‘Natural Killer (NK) cells’ (part of the ‘innate’ immune system) and levels of ‘T-cells’ and ‘B-cells’. 

T-cells and B-cells are types of white blood cell produced as part of the body’s ‘acquired’ or ‘adaptive’ immune response. B-cells fight bacteria and viruses by making Y-shaped proteins called antibodies. They are specific to each pathogen and are able to lock onto the surface of an invading cell and mark it for destruction by other immune cells. T-cells are involved in killing cells that have been invaded by pathogens such as the SARS-CoV-2 virus, which gives us COVID-19. The researchers also measured levels of six proteins called ‘cytokines’ that are produced by immune cells as chemical messengers; they’re known as ‘cell-signalling’ proteins and help regulate the immune response.

What were the results of this study?

The researchers compared the blood test results of the two groups of COVID-19 patients plus the control group using statistics to look for any significant differences. A key finding was that the ratio of two white blood cell types was affected in patients with COVID-19. Called the ‘neutrophil to lymphocyte ratio’ or ‘NLR’, this measure is known to be a more sensitive indicator of inflammation than measuring the number of each cell type individually. In this study this ratio was found to be increased moderately in COVID-19 patients with mild symptoms, and increased profoundly in those patients with severe symptoms, compared with the control group.

The researchers also found differences in T-cells between the three groups of patients – COVID-19 patients had significantly lower total numbers of T-cells compared with the control group but there was no statistical difference in total T-cells between mild and severe COVID-19 patients. One group of T-cells called ‘Tregs’ (short for ‘Regulatory T-cells’) were shown to be increased in the blood of patients with mild COVID-19 compared with the control group. Tregs regulate the immune response in the body.

The results also indicated a significantly lower number of NK cells and B-cells in the blood of severely ill COVID-19 patients compared with the control group. Three cytokines were found to be elevated in patients with severe disease compared with the mild patients and the control group, including C-reactive protein (CRP), which is made by the liver and is a sensitive marker of inflammation.

What can we conclude from this study?

This study provides useful data on how different elements of the human immune system respond to COVID-19, and indicates possible reasons behind differences in how severely some people are affected by the virus compared with others. It is important to note that the results are from a small sample group of patients so cannot be assumed to be indicative of immune response in all COVID-19 patients. However, the results do suggest certain trends in blood test results of patients with severe COVID-19 compared with patients with milder cases and with those who do not have COVID-19. For example, the increased levels of ‘Tregs’ in patients with COVID-19 could indicate an active anti-inflammatory response by those patients’ immune systems. The researchers recommend further investigation of the activity and function of those immune cells and proteins found to be lower or higher in severely ill COVID-19 patients. Testing for these in larger groups of patients will increase understanding of the immune system’s response to COVID-19, and could help identify predictive tests that can indicate who is more likely to become seriously ill with the virus. 

Tan, M., Liu, Y., Zhou, R., Deng, X., Li, F., Liang, K. and Shi, Y. (2020), Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. Immunology. Accepted Author Manuscript. doi:10.1111/imm.13223

First published 27 May 2020

Summary author Penny Fletcher