Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model
Authors: Poliquin Guillaume , Funk Duane , Jones Shane , Tran Kaylie , Ranadheera Charlene , Hagan Mable , Tierney Kevin , Grolla Allen , Dhaliwal Amrinder , Bello Alexander , Leung Anders , Nakamura Cory , Kobasa Darwyn , Falzarano Darryl , Garnett Lauren , Bovendo Hugues Fausther , Feldmann Heinz , Kesselman Murray , Hansen Gregory , Gren Jason , Risi George , Biondi Mia , Mortimer Todd , Racine Trina , Deschambault Yvon , Aminian Sam , Edmonds Jocelyn , Sourette Ray , Allan Mark , Rondeau Lauren , Hadder Sharron , Press Christy , DeGraff Christine , Kucas Stephanie , Cook Bradley W. M. , Hancock B. J. , Kumar Anand , Soni Reeni , Schantz Darryl , McKitrick Jarrid , Warner Bryce , Griffin Bryan D. , Qiu Xiangguo , Kobinger Gary P. , Safronetz Dave , Stein Derek , Cutts Todd , Kenny James , Soule Geoff , Kozak Robert , Theriault Steven , Menec Liam , Vendramelli Robert , Higgins Sean , Liu Guodong , Rahim Niaz Md , Kasloff Samantha , Sloan Angela , He Shihua , Tailor Nikesh , Gray Michael , Strong James E. 
Published: September 2019

Background

There are currently limited data for the use of specific antiviral therapies for the treatment of Ebola virus disease (EVD). While there is anecdotal evidence that supportive care may be effective, there is a paucity of direct experimental data to demonstrate a role for supportive care in EVD. We studied the impact of ICU-level supportive care interventions including fluid resuscitation, vasoactive medications, blood transfusion, hydrocortisone, and ventilator support on the pathophysiology of EVD in rhesus macaques infected with a universally lethal dose of Ebola virus strain Makona C07.

Methods

Four NHPs were infected with a universally lethal dose Ebola virus strain Makona, in accordance with the gold standard lethal Ebola NHP challenge model. Following infection, the following therapeutic interventions were employed: continuous bedside supportive care, ventilator support, judicious fluid resuscitation, vasoactive medications, blood transfusion, and hydrocortisone as needed to treat cardiovascular compromise. A range of physiological parameters were continuously monitored to gage any response to the interventions.

Results

All four NHPs developed EVD and demonstrated a similar clinical course. All animals reached a terminal endpoint, which occurred at an average time of 166.5 ± 14.8 h post-infection. Fluid administration may have temporarily blunted a rise in lactate, but the effect was short lived. Vasoactive medications resulted in short-lived improvements in mean arterial pressure. Blood transfusion and hydrocortisone did not appear to have a significant positive impact on the course of the disease.

Conclusions

The model employed for this study is reflective of an intramuscular infection in humans (e.g., needle stick) and is highly lethal to NHPs. Using this model, we found that the animals developed progressive severe organ dysfunction and profound shock preceding death. While the overall impact of supportive care on the observed pathophysiology was limited, we did observe some time-dependent positive responses. Since this model is highly lethal, it does not reflect the full spectrum of human EVD. Our findings support the need for continued development of animal models that replicate the spectrum of human disease as well as ongoing development of anti-Ebola therapies to complement supportive care.