"EVIDENT has achieved the following results:
1. Immune response of survivors: We have assessed the antibody titers, including neutralising antibodies, and T cell reactivity in survivors. The neutralising antibody titers remain stable after discharge for long periods of time (at least a year). Glycoprotein antibodies as measured in ELISA can serve as a surrogate for neutralising activity. As survivors are supposedly protected from re-infection, the observed level of antibody and T cell response should be considered protective.
2. Management of patients: Set up of clinical chemistry measurement in the field revealed frequent renal failure, electrolyte disturbance, and evidence for bacterial super-infection. Main co-infection was malaria, while chronic virus infections were rare. Age, virus load, and co-infection with malaria in children 5-14 years of age are independent predictors of poor outcome.
3. Ebola virus evolution: Our deep sequencing program revealed the evolutionary history and molecular clock of the virus during the epidemic with multiple spreading events of the virus across country borders. Furthermore, we established nanopore sequencing technology in Guinea to follow the molecular epidemiology of the virus in real-time and support field epidemiology and contact tracing efforts. Replicon and reverse genetics systems were established to study the consequences of virus mutations that emerged during the epidemic.
4. Pathophysiology and immunology of EVD: We have measured a wide range of soluble cytokines, chemokines and growth factors, and studied the T, Vδ2T, and NK cell response during acute infection. Fatal and surviving EVD patients showed robust T cell activation consistent with biomarker analysis. However, in fatal patients markers of T cell ‘exhaustion’, in particular CTLA-4 and PD-1, were upregulated demonstrating that defects in the T cell homeostasis are associated with poor outcome of EVD.
5. Virus persistence and shedding: We found that essentially all body fluids contain virus RNA until convalescence. Virus persists after convalescence in breast milk and seminal fluid. Time to clearance of EBOV RNA from seminal fluid is variable and may be >10 months.
6. Exploitation and dissemination: Results of EVIDENT have been presented to national authorities to facilitate outbreak response; to WHO to be considered in guidelines; to pharmaceutical companies to guide in the development of EVD vaccines; and to the wider scientific community at international conferences. The data have been published in high-ranking scientific journals, including ""Nature"". Thus far, 16 articles are published or in press.
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