Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6

Background: The immune response to SARS-CoV-2 is essential for control and resolution of infection, but when dysregulated it may cause immunopathology. Inflammatory cytokine storm in severe cases of novel coronavirus disease (COVID-19) is associated with extensive lung tissue damage that may rapidly evolve towards severe respiratory failure. Laboratory hallmarks in COVID-19 patients are decreased white cell blood counts, lymphocytopenia, increased D-dimer and C reactive protein (CRP). The aim of our study was to evaluate the usefulness of testing serum IL-6, alone and together with other serological and clinical biomarkers, to predict short-term negative clinical course of COVID-19 patients admitted to a non critical hospital setting.Methods: This is an observational retrospective study including 208 patients with COVID-19, classified as moderate (n=91, 43.8%) or severe (n=117, 56.2%), with no immediate need of ventilatory assistance. Clinical and laboratory findings were reviewed and analysed by using survival analysis and logistic regression modelling with a LASSO procedure for variable selection. In particular, we used 3-day worsening as an outcome in a logistic model to generate a prognostic score.Findings: In our case series, 131/208 patients (62.9%) displayed abnormal IL-6 serum level (>10 pg/ml) (mean value ± SD: 27±40.9). Clinical worsening including death (n=16) and the need for non-invasive mechanical ventilation or ICU (n=46) occurred in 62 patients, of whom 45 worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels at admission [Hazard Ratio (HR): 8.2, 95%CI: 2.5 – 27.3 for the highest vs. lowest quartile]. Although IL-6 moderately correlated with other parameters, the multivariate logistic model showed that IL-6 (p=0.002), SaO2/FiO2 ratio (p<0.001) and CRP (p=0.014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an AUC=0.887 (95%CI 0.838 – 0.935) and also showed good performance to predict 2-day (AUC=0.885), 4-day (AUC=0.873) and 7-day worsening (AUC= 0.857). Finally, a nomogram predicting the probability of 3-day worsening was generated.Interpretation: Combining clinical and laboratory findings (SaO2/FiO2 ratio, IL-6 and CRP) upon admission may be useful in the early identification of moderate-to-severe COVID-19 patients at high risk for further clinical deterioration.Funding Statement: None.Declaration of Interests: All the Authors declare no competing interests.Ethics Approval Statement: The procedures followed in the study were approved by the Local Ethical Committee (protocol 16859).