In a case study published in Science Translational Medicine, researchers describe what they believe is the host response to the blood-borne disease that has plagued several countries in Africa and caused world-wide panic.
Although there is still no cure for infection with the Ebola virus, the disease that spread through West Africa in 2014-2015 and caused a worldwide, media-fueled panic, researchers seem to have identified key parameters for its treatment.
The World Health Organization reported that the most recent West African outbreak, which centered on Guinea, Liberia and Sierra Leone, caused more than 28,000 illnesses and claimed more than 11,000 lives. Experts believe the outbreak was caused by a Makona variant of the Ebola virus, which has a 40% fatality rate.
In a case study published April 12, 2017, by the journal Science Translational Medicine, a research team from the National Institutes of Health (NIH) and other institutions described what they called “unprecedented detail on the host response to Ebola.” According to an NIH statement, they believe their findings “may inform the development of therapeutics designed to boost or accelerate host factors that most effectively counter the virus and promote healing.”
The NIH researchers measured daily global gene expression responses in peripheral blood samples collected from a 34-year-old male healthcare worker exposed to Ebola in Sierra Leone, using Pearson correlation and principal components analyses to identify key transition points. They mapped gene ontology and the pathway of the transition points, as well as the gene expression response, “to characterize host responses that correlated with [Ebola], including replication of virus in peripheral blood leukocytes, serum viral load, coagulopathy, critical illness, and recovery.” The health worker in this case had been evacuated to the NIH on day 7 of his illness and received supportive care (but no experimental therapies). He cleared the virus and was released on day 33.
In general, according to the NIH statement, the research team found changes in antiviral and immune response genes that effectively identified key transition points in the patient’s response to infection. These included a significant decline in antiviral responses, which corresponded to clearance of the virus from white blood cells. Their analysis of this patient also revealed that most of the identified host responses “shifted rapidly from activation of genes involved in cell damage and inflammation toward those linked to promotion of cellular and organ repair.” Indeed, the expression levels of certain lymphocyte activation markers (FasLG, granzyme K, and ICOS), “natural killer” markers (KLRB1, KLRC3, and KLRD1), and T lymphocyte markers (CD3D, CD83, CD8A, CD8B, and IL2RB) generally decreased from day 9 of illness to day 14/15 before starting to increase again until day 18/19.
“This pivot came before the first signs of clinical improvement in the patient,” the NIH statement notes.
Although the patient was still seriously ill by day 21, the day marked what the authors describe as a “further transition in the equilibrium between damage and repair responses that coincided with detection of neutralizing antibodies.” They write that the patient’s recovery corresponded to “an overall decrease in infection-correlated gene expression responses that persisted from discharge on day 33 through day 270 of follow-up, with observed flare-ups of peripheral blood leukocyte gene expression responses on days 59 and 103, although these samples were negative for Ebola virus glycoprotein RNA.
“This study was limited to a detailed characterization of daily changes in peripheral blood leukocyte gene expression responses in a single patient from early symptomatic disease to critical illness and through recovery,” they write. “While adding to our understanding of this patient’s disease, it remains to be shown how it applies in the larger context of human Ebola virus disease, including both survivors and fatalities. Nonetheless, it highlights the benefits of supportive medical care, as well as the need to perform larger host response studies. Although we observed similarities between this patient and studies in nonhuman primates, we also identified several important differences such as a lack of a pronounced ‘cytokine storm’ and absence of pronounced lymphopenia during peak illness in this patient. Improving our ability to reduce severity and high mortality rates of Ebola virus disease will increasingly rely on studies that integrate critical care medicine and detailed, longitudinal host response studies in both humans and nonhuman primates.”
Brian P. Duleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.