Research ArticleEMERGING INFECTIONS

Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease

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Science Translational Medicine  12 Apr 2017:
Vol. 9, Issue 385, eaai9321
DOI: 10.1126/scitranslmed.aai9321

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The evolving Ebola virus host response

Although the Ebola virus sporadically causes outbreaks in humans, there is a relative paucity of information regarding the dynamics of the immune response in patients. During the recent outbreak, a health care worker with severe Ebola virus disease was evacuated to the NIH Clinical Center, where he received supportive care and had longitudinal blood samples drawn up to almost a year after infection. Kash et al. performed transcriptomic analyses on these blood samples to see how his body responded to the virus through the different phases of infection and recovery, and compared them to clinical symptoms and viral loads. These valuable data provide insights into Ebola pathogenesis and could help guide future treatments.

Abstract

The 2013–2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration–approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance.

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