The role of IL-6, ferritin, and coagulopathy in Covid-19 clinical progression [version 2; peer review: 2 approved]

Background In Covid-19 infection, the release of pro-inflammatory mediators in the setting of cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary intravascular thrombosis and eventually systemic coagulopathy. However, the relationship between IL-6 and coagulopathy remains unclear in Covid-19 progression. We aimed to investigate the correlation of IL-6 with D-dimer, fibrinogen, prothrombin time (PT), and ferritin. Furthermore, we also analysed the changes of those parameters in relation with progression of Covid-19 disease. Methods A prospective cohort study was conducted in moderate and severe Covid-19 patients from June 2020 to January 2021. A serial evaluation of IL-6, D-dimer, fibrinogen, ferritin, and PT was performed and correlated with the patient's condition at admission and on the 14th day. The outcomes (improvement, worsening, or discharged patients) were recorded during the study. Results Of 374 patients, 73 study subjects (61 severe and 12 moderate Covid-19) were included in this study. A total of 35 out of 61 severe illness and one out of 12 moderate illness subjects had experienced worsening. Spearman-rank correlation of IL-6 with with ferritin, D-dimer, fibrinogen, and PT was 0.08 ( p=0.5), −0.13 ( p=0.27), 0.01 ( p=0.91), and 0.03 ( p=0.77), respectively. In ROC analysis, D-dimer (74,77%) and IL-6 (71,32%) were the highest among other variables (>60%). Conclusions In Covid-19 patients, there was a correlation between elevated IL-6 and D-dimer levels with clinical deterioration. There was no correlation between elevated IL-6 levels with ferritin, D-dimer, fibrinogen, and PT levels. In conclusion, changes in IL-6 and D-dimer can be independent predictor of disease progression in moderate and severe Covid-19 patients.