Longitudinal COVID-19 profiling associates IL-1Ra and IL-10 with disease severity and RANTES with mild disease.

Background Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation and drug development. Here we present a temporal analysis of key immune mediators, cytokine and chemokines in blood of hospitalised COVID-19 patients from serial sampling and follow up over four weeks.Methods A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an hospital in China with either mild (53 patients) or severe disease (18 patients) were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines and chemokines in peripheral blood every 4-7 days over one month per patient using a bio-plex multiplex immunoassay.Results We found that the chemokine RANTES(CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1Ra and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-gamma were only significantly elevated in the late stage of severe COVID-19 illness. TNF- alpha and GM-CSF showed no significant differences between severe and mild cases.Conclusion Together our data suggest early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1Ra, IL-10 in blood individually and in combination might be useful prognostic bio-markers to guide treatment strategies.