Interleukine 6 is associated with severity and poor outcome in ICU-patients with SARS-CoV-2 infection

ABSTRACT

Background-aim: SARS coronavirus 2 (SARS-CoV-2) is responsible for high morbidity and mortality worldwide, mostly due to the exacerbated inflammatory response observed in critically ill patients. However, little is known about the kinetics of the systemic immune response and its association with survival in Covid-19 patients admitted in ICU Methods: We performed a retrospective multicenter study including all patients with SARS-Cov-2 infection admitted in 3 ICUs between March 1st and April 15th 2020, with at least 2 measurements of Interleukin 6 (IL6) in 4 days (baseline and day 3-4). Patients who received immunomodulatory treatment were excluded. IL6 was measured on serum by ELISA (Quantikine R&D Systems) and results were expressed at median [25th – 75th percentile]. The relationship between IL6 and CRP, organ failure severity (SOFA score) or in-ICU mortality was analyzed. Results: From the 140 patients admitted in the 3 ICU for SARS-Cov2 infection (PCR diagnosis), 101 patients were included, the mean age was 59 ± 11 years with a high proportion of men (82%). Patients had severe respiratory disease with media SOFA score of 4 [3-7] and 83 required endotracheal intubation/mechanical ventilation at baseline. An increase of SOFA score between baseline and day3-4 was observed in 32 patients (worsening group). Baseline measurements were done 14 days [11-20] after onset of symptoms. At the end of the study, on April 15th 2020, 47 patients had been discharged from ICU, 35 were still in ICU, and 19 had died in ICU. Baseline IL6 concentrations were positively associated with SOFA score. Moreover, baseline IL-6 and CRP concentrations were significantly higher in the worsening group vs the non-worsening 278 [70-622] vs 71 [29-153] pg/mL (P<0.01) for IL6 and 178 [100-295] vs 100 [37-213] mg/L (P<0.05) for CRP. However, IL6 concentrations were not correlated with CRP. Il6 and CRP concentrations were higher in non-survivors at baseline and at day 3-4. CRP significantly decreased in survivors (190 [80-248] to 108 [45-185], P<0.05) whereas IL6 decreased in both groups. Conclusions: In this multicenter cohort of ICU patients with SARS-CoV-2 infection, we found that Il6 was associated with organ failure severity, worsening and poor outcome.