A Novel Hyperinflammation Clinical Risk Tool, HI5-NEWS2, Predicts Mortality Following Early Dexamethasone Use in an Observational Cohort of Hospitalised COVID-19 Patients

Abstract

Background: The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19.Methods: Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status.Findings: Of 1265 patients, high risk of HI (high HI5-NEWS2) (n=367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, pInterpretation: The HI5-NEWS2 measured at COVID-19 diagnosis, strongly predicts mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention.Clinical Trial Registration Details: Clinicaltraisl.gov ID: NCT04903834Funding Information: No external funding.Declaration of Interests: None of the authors declare any conflicts of interest relevant to this work.Ethics Approval Statement: UK NHS ethical approval from Health and Care Research Wales, IRAS 286016. The study followed the principles of the Declaration of Helsinki and was approved by the National Research Ethics Service (Identification of Novel Factors Leading to Activated Macrophage Expansion in COVID19 and related conditions to guide targeted intervention, INFLAME COVID-19 Study, NRES 286016).