Mapping the recovery of critically ill COVID19 patients by high-dimensional profiling identifies blood immunotypes following a specific immune trajectory
Abstract
The COVID-19 pandemic poses a major burden on health-care and economic systems across the globe. Even though a majority of the population only develops minor symptoms upon SARS-CoV2 infection, a significant proportion are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are gradually expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. We have analyzed longitudinally collected, whole blood samples of 40 surviving COVID-19 patients during their recovery at ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil to lymphocyte ratio (NLR), we defined 4 sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We also identified classical monocytes as the first immune cell type to recover by restoring HLA-DR-positivity and by reducing the immunosuppressive CD163+ monocyte population, followed by the recovery of CD8+ and CD4+ T cell, and mDC populations. The determined immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.
Biosketch
Dena Panovska is a PhD student at the Department of Imaging and Pathology at KULeuven, Belgium. She is part of the Laboratory for Precision Cancer Medicine (LPCM) located at Gasthuisberg, University Hospital Leuven (UZLeuven).
The mass cytometry skills gained in her glioblastoma research translated to her recent focus on the SARSCoV2 pandemic in monitoring the functionality and restoration of major immune populations in critically ill COVID19 patients during their recovery phase.
Keywords
Functional diagnostics, glioblastoma, longitudinally collected samples, COVID19
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