Long-lasting severe immune dysfunction in Ebola virus disease survivors

埃博拉病毒病幸存者长期存在严重的免疫功能障碍

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作者:Aurélie Wiedemann ,Emile Foucat ,Hakim Hocini ,Cécile Lefebvre ,Boris P Hejblum ,Mélany Durand ,Miriam Krüger ,Alpha Kabinet Keita ,Ahidjo Ayouba ,Stéphane Mély ,José-Carlos Fernandez ,Abdoulaye Touré ,Slim Fourati ,Claire Lévy-Marchal ,Hervé Raoul ,Eric Delaporte ,Lamine Koivogui ,Rodolphe Thiébaut ,Christine Lacabaratz ,Yves Lévy

Abstract

Long-term follow up studies from Ebola virus disease (EVD) survivors (EBOV_S) are lacking. Here, we evaluate immune and gene expression profiles in 35 Guinean EBOV_S from the last West African outbreak, a median of 23 months (IQR [18-25]) after discharge from treatment center. Compared with healthy donors, EBOV_S exhibit increases of blood markers of inflammation, intestinal tissue damage, T cell and B cell activation and a depletion of circulating dendritic cells. All survivors have EBOV-specific IgG antibodies and robust and polyfunctional EBOV-specific memory T-cell responses. Deep sequencing of the genes expressed in blood reveals an enrichment in 'inflammation' and 'antiviral' pathways. Integrated analyses identify specific immune markers associated with the persistence of clinical symptoms. This study identifies a set of biological and genetic markers that could be used to define a signature of "chronic Ebola virus disease (CEVD)".

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