Long-lasting severe immune dysfunction in Ebola virus disease survivors

Abstract Clinical follow-up of Ebola virus disease (EVD) survivors revealed a persistence of clinical symptoms and higher risk of mortality. Long-term analyses of the immune and inflammatory profiles of EVD survivors are currently lacking. Here, we evaluate immune profile status and gene expression profiles in 35 Guinean EVD survivors (EBOV_S) from the last West African outbreak, a median of 23 months (IQR [18-25]) after discharge from the Ebola treatment center. We show a persistent increase of several biomarkers of inflammation, immune activation and gut tissue damage in EBOV_S compared to healthy donors living in the same area. These results are confirmed by phenotypic characterization of immune cell subsets revealing increases in activation marker expression and the frequencies of CD8 + T cells, exhausted B cells, non-classical NK cells and circulating dendritic cells. All survivors have EBOV-specific IgG antibodies and robust and polyfunctional EBOV-specific memory T-cell responses. Deep sequencing studies of the genes expressed in blood revealed a significant enrichment in genes associated with antiviral responses in EBOV_S. This study assess the long-term persistence of immunological dysfunction in survivors and identify a set of biological and genetic markers that could be used to define a signature of “chronic Ebola virus disease (CEVD)”.