Functional immunoparalysis characterized by elevated Interleukin-10 and Interleukin-10- to-Lymphocyte Count Ratio is associated with severe disease and poor outcomes in coronavirus disease 2019 (COVID-19)

ABSTRACT Objectives Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state, called cytokine storm. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response which if severe may lead to a state of functional immunoparalysis. The aim of this study was to evaluate the anti-inflammatory response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with patient outcomes. Methods Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was peak COVID-19 severity within 30 days of index ED visit. Additional endpoints included COVID-19 severity at ED disposition, development of severe acute kidney injury (AKI) or secondary bacterial infections. Results A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease at both time points (all p<0.05), as well as in those who developed severe AKI and secondary bacterial infection (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 was associated with 42% increased odds of severe COVID-19 (p=0.031), whilst a one-unit increase IL-10/lymphocyte ratio was also associated with 32% increase in odds of severe COVID-19 (p=0.013). Conclusions The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of secondary bacterial infections. IL-10 and IL-10/lymphocyte ratio at ED presentation were independent predictors of COVID-19 severity. Functional immunoparalysis in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.