Immunophenotyping for Risk Stratification of Patients with COVID-19

Abstract

Treating COVID-19 remains challenging, in part due to limited understanding of severe immunopathology. We performed a holistic and unbiased analysis of 17 immune cell types using flow cytometry immunophenotyping in 802 blood samples from 513 COVID-19 patients obtained at presentation and follow-up, 44 cases with other infection and 36 healthy donors. After adjusting to the corresponding age-range, we found that most COVID-19 patients showed normal patterns of immune response to infection. However, 14% displayed an immune signature at presentation with skewing of all cell types except neutrophils and plasmablasts, which was significantly associated with severe outcome. Divergent immune trajectories were observed in 8 cell types of cases with favorable vs fatal outcome. B-cells had the strongest impact in patients’ survival and, together with non-classical monocytes, had independent prognostic value regardless of age and comorbidities. Collectively, these results shed light into the immunopathology of COVID-19 and provide new tools for risk-stratification.Funding: This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI17/01243), Fondo Europeo de Desarrollo Regional (FEDER) and Asociación Española Contra el Cáncer (FCAECC, Predoctoral Grant Junta Provincial Navarra). This study was supported internationally by the Cancer Research UK, FCAECC and AIRC under the Accelerator Award Programme, and the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT). Conflict of Interest: The authors declare no competing conflict of interest.Ethical Approval: The Clinica Universidad de Navarra Ethics Committee approved the protocol and informed consent forms, required prior to patient enrollment. The study was conducted per the ethical principles of the Declaration of Helsinki.