Point-of-Care Inflammatory Phenotyping Predicts Clinical Outcome in COVID-19

Rationale: The COVID-19 pandemic has led to more than 445,000 deaths worldwide. There is an urgent need for effective treatment. Studies suggest that a hyper-inflammatory response is a major cause of disease severity and death. Using precision medicine to rapidly identify patients with COVID-19 with hyper-inflammation may be key for identify subgroups who may benefit from targeted immunomodulatory treatments. Methods: In combination with a diagnostic point-of-care test (POCT), we used a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 101 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton. Demographic, clinical, laboratory and outcome data were collected for all patients. Findings: Age over 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). Cytokines IL-6, IL-8, TNF-α, IL-1β and IL-33 were significantly associated with adverse outcome in COVID-19. Clinical parameters at admission were predictive of poor outcome (AUROC 0.71), with addition of a combined cytokine panel significantly improving the predictability (AUROC 0.85). In those < 70 years, IL-33 and TNF-α were predictive of poor outcome (AUROC 0.84 and 0.83), and addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). Interpretation: A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Rapid identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19. Funding Statement: No external funding was received for this work. The parent study is supported by QIAGEN in the form of discounted equipment and consumables. They had no role in the study conception, design, data analysis or manuscript preparation. Declaration of Interests: Authors HB, AF, BS, NB, SP, FB, SW, NS, CMS, KJS and DC have no conflicts of interest to declare. Author TWC reports personal fees from BioMerieux and BioFire LLC, non-financial support from BioMerieux and BioFire LLC, personal fees from Synairgen research ltd, personal fees and other from Roche, personal fees from Cidara therapeutics, personal fees from Janssen , grants from NIHR, all outside the submitted work. Author TMAW reports personal fees and other from MMH, grants and personal fees from GSK, grants and personal fees from AZ, personal fees from BI, grants and personal fees from Synairgen, all outside the submitted work. Ethics Approval Statement: The study was approved by the South Central Hampshire A Research Ethics Committee: REC reference 20/SC/0138, on the 16th March 2020.