Interleukin-6, procalcitonin and neutrophil-to-lymphocyte ratio: Potential immune-inflammatory parameters to identify severe and fatal forms of COVID-19

Sayah, Wafa; Berkane, Ismahane; Guermache, Imène; Sabri, Mohamed; Zahra Lakhal, Fatma; Yasmine Rahali, Sarah; Djidjeli, Asma; mahammad Lamara, Lydia; Merah, Fatma; Belaid, Brahim; Berkani, Lilya; Zhor Lazli, Nouzha; Kheddouci, Lylia; Kadi, Ahmed; Ouali, Mourad; Khellafi, Rachida; Mekideche, Dalila; Kheliouen, Assia; Malek Hamidi, Réda; Ayoub, Soraya; Beramtane raaf, Nabil; Derrar, Fawzi; Gharnaout, Merzak; Allam, Ines; Djidjik, Réda

Accumulating evidencesupports thatthe viral-induced hyper-inflammatory immune response plays a central role in COVID-19 pathogenesis. It might be involvedin the progression to acute respiratory distress syndrome (ARDS), multi-organ failure leading to death. In this study, we aimed to evaluate the prognostic value of the immune-inflammatory biomarkersin COVID-19, then determine optimal thresholds for assessing severe and fatal forms of this disease.153 patients with confirmed COVID-19 were included in this study, and classified into non-severe and severe groups. Plasmatic levels of interleukin 6 (IL6), C-reactive protein (CRP), soluble-IL2 receptor (IL2Rα), procalcitonin (PCT) and ferritin were measured using chemiluminescence assay. Complete blood count was performed by Convergys 3X® hematology analyzer. Our results demonstrated that the peripheral blood levels of IL6, PCT, CRP, ferritin, IL2Rα, white blood cell count (WBC), neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) were significantly higher in severe forms of COVID-19. The ROC curve analysis showed that IL6 was the most accurate inflammatory biomarker. The calculated cutoff of IL6 (42 pg/ml) could correctly classify more than 90% of patients regarding their risk of severity (area under ROC curve (AUROC) =0.972) and the threshold value of 83 pg/ml was highly predictive of the progression to death (AUROC =0.94, OR=184) after a median of 3 days. Besides, IL-6 was positively correlated with other inflammatory markers and the kinetic analysis highlighted its value for monitoring COVID-19 patients. PCT and NLR had also a high prognostic relevance to assess severe forms of COVID-19 with corresponding AUROC of 0.856, 0.831 respectively. Furthermore the cut-off values of PCT (0.16 ng/ml) and NLR (7.4) allowed to predict mortality with high accuracy (se=96.3%, sp=70.5 %,OR=61.2) , (se=75 %, sp=84 %, OR=14.6).The levels of these parameters were not influenced by corticosteroid treatment, which make them potential prognostic markers when patients are already undergoing steroidtherapy.