Inflammatory mediators of severity in COVID-19 infection

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The host inflammatory response to SARS-CoV-2 infection contributes towards the lung injury seen in patients with COVID-19. However, the pathways involved, how they impact disease severity, and how they relate to inflammatory responses seen in other viral lung infections, remain poorly understood. Identifying mediators that reflect disease severity might allow for the definition of ‘treatable traits’, and the stratification of patients into the most appropriate clinical care pathways.

A recent publication in Science Immunology, drawing on clinical data from the ISARIC4C study, represents the largest investigation to date of inflammatory and disease markers in COVID-19. Using data from such a substantial cohort enabled the research team to examine a broad range of immune responses, and look for correlates with differing COVID-19 disease severity.

The research teams found that severe COVID-19 infection was closely associated with raised levels of a number of plasma markers indicative of endothelial activation, coagulation and inflammation, including Interleukin-6 (IL-6), the antiviral immune mediator and leukocyte recruitment factor CXCL10 and the myeloid cell growth factor GM-CSF.

IL-6 was significantly raised in patients who had been hospitalised due to the severity of their COVID-19, in line with previous reports on this cytokine as a disease marker. IL-6 was also found to be significantly elevated in data from fatal influenza infections, suggesting that inhibition of IL-6 might be an effective treatment target for both SARS-CoV-2 and severe influenza infection. Interestingly, whilst GM-CSF was also found to be was closely associated with disease severity, being significantly raised in fatal cases of COVID-19 infection, elevated levels were not seen in fatal cases of influenza. Importantly, elevated levels of GM-CSF, and many of other identified mediators, were noted within a few days of the initial onset of symptoms, indicating that such pathways may play a role in disease propagation.

The results of the study suggest that the measurement of plasma IL-6 and GM-CSF levels may allow for patient stratification, potentially allowing the early use of treatments in patients who will otherwise go on to develop severe disease.

Links

Publication in Science Immunology DOI: 10.1126/sciimmunol.abg9873

Prof Yanick Crow's Research Group