Discovery of circulating biomarkers in COVID 19 patients undergoing anti IL6R immunotherapy

Background: The severe pneumonitis in coronavirus disease 2019 (COVID-19) requires prolonged treatment in intensive care units, leading to overwhelmed hospital facilities Treatment with tocilizumab (Actemra, Roche), a monoclonal antibody targeting interleukin 6 receptor (IL6R), has shown promising efficacy in alleviating the severe pneumonitis However, only around 50% of the treated patients benefit from this intervention It is therefore an unmet medical need to identify biomarkers associated with the severity of disease and theranostic biomarkers to predict and differentiate potential responders from non-responders to the treatment Methods: An unbiased hyper reaction monitoring mass spectrometry (HRM™-MS) approach was used to analyze serum samples from severe COVID-19 cases before and 7 days after treatment with tocilizumab (n = 28), enabling simultaneous identification and quantification of all detectable serum proteins All samples were measured using 1h gradient on a nano-flow LC-MS/MS setup operated in data-independent acquisition (DIA) mode Data was extracted using Spectronaut™ (Biognosys) Univariate and multivariate statistical analyses were conducted to identify biomarker candidates Pathway analysis was used to identify dysregulated biological functions and signaling pathways Results: Over 450 proteins were quantified across all samples by HRM-MS Univariate statistical analysis identified significantly changing proteins across conditions (mortality day 30, pre-post treatment, responder/non-responder, q-value \u003e 0 05 and fold change \u003e1 5) Multivariate analysis (PLS-DA) was also used to classify proteins based on their abundance across condition Proteomic data was further integrated with clinical outcome data to identify a panel of protein biomarker candidates potentially useful in predicting tocilizumab treatment efficiency and the COVID-19 disease severity Conclusions: Unbiased proteomic profiling of COVID-19 patient serum identified a panel of candidate protein biomarkers that associate with tocilizumab treatment response as well as the ensuing course of the disease Further validation of these biomarker candidates opens the way for a personalized medicine approach in treating COVID-19 Legal entity responsible for the study: Biognosys AG Funding: Biognosys AG Disclosure: J-M Michot;F-X Danlos;F Pommeret;A Marabelle: Full/Part-time employment: Institut Gustave Roussy V Dozio;E Kishazi;C Escher;K Kakalacheva - Beeler: Full/Part-time employment: Biognosys AG M Vasse;J Rohmere;M Roumier: Full/Part-time employment: Hopital Foch