Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients

Abstract

<jats:p>The pandemic Coronavirus-disease 19 (COVID-19) is characterized by a heterogeneous clinical course. While most patients experience only mild symptoms, a relevant proportion develop severe disease progression with increasing hypoxia up to acute respiratory distress syndrome. The substantial number of patients with severe disease have strained intensive care capacities to an unprecedented level. Owing to the highly variable course and lack of reliable predictors for deterioration, we aimed to identify variables that allow the prediction of patients with a high risk of respiratory failure and need of mechanical ventilation Patients with PCR proven symptomatic COVID-19 infection hospitalized at our institution from 29th February to 27th March 2020 (n=40) were analyzed for baseline clinical and laboratory findings. Patients requiring mechanical ventilation 13/40 (32.5%) did not differ in age, comorbidities, radiological findings, respiratory rate or qSofa score. However, elevated interleukin-6 (IL-6) was strongly associated with the need for mechanical ventilation (p=1.2.10<jats:sup>-5</jats:sup>). In addition, the maximal IL-6 level (cutoff 80 pg/ml) for each patient during disease predicted respiratory failure with high accuracy (p=1.7.10<jats:sup>-8</jats:sup>, AUC=0.98). The risk of respiratory failure for patients with IL-6 levels of ≥ 80 pg/ml was 22 times higher compared to patients with lower IL-6 levels. In the current situation with overwhelmed intensive care units and overcrowded emergency rooms, correct triage of patients in need of intensive care is crucial. Our study shows that IL-6 is an effective marker that might be able to predict upcoming respiratory failure with high accuracy and help physicians correctly allocate patients at an early stage.</jats:p>

Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome

“…It is tempting to speculate that the CD8 + cytotoxic T-cells are predominantly responsible for the production of IFNg, whereas virus-specific CD4 + T-cells could be responsible for the production of typical Th1 and Th2 cytokines. Elevated levels of IL-6 in patient plasma have previously been correlated to respiratory failure in COVID-19 patients 11 . Here, we could not detect increased specific production of IL-6 in PBMC stimulated with peptide pools, suggesting that virus-specific T-cells are not to blame for the production of IL-6 and the concomitant 'cytokine storm', but that these are predominantly mediated by innate immune cells.…”

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

“…Importantly, the lung tissue and gut enterocyte programs include the gene encoding the IL6 co-receptor (IL6ST), and the AT2 cell program includes IL6. IL6 signaling has been implicated in uncontrolled immune responses in the lungs of COVID19 patients, elevated serum IL6 levels are associated with the need for mechanical ventilation 92 , and anti-IL6R antibodies (tocilizumab) are being tested for clinical efficacy in COVID-19 patients. Indeed, IL6ST and IL6 are higher in dual positive vs. dual negative AT2 cells (Extended Data Fig.…”

Weathering the Cytokine Storm in Susceptible Patients with Severe SARS-CoV-2 Infection

“…One non peer reviewed study in severe COVID-19 infection found that the risk of respiratory failure in patients with maximal circulating IL-6 levels >80 pg/mL was 22-fold higher with a median time to mechanical ventilation of 1.5 days. 23 A more selective approach is therefore required to address the downstream cytokine storm. Recent attention has centered around the possibility of therapeutic intervention with anti-IL-6 drugs such as tocilizumab and sarilumab that are indicated for rheumatoid disease.…”