In a groundbreaking study published on Feb. 9, 2022, scientists described how Ebola persists in certain areas of the body, where it can re-emerge and cause deadly disease — even long after treatment with monoclonal antibodies. Their study, which used a non-human primate model of Ebola virus infection, has been published in the journal Science Translational Medicine.
Dr Kevin, the paper's senior author, said some of the recent outbreaks of EVD in Africa were linked to persistent infections in patients who survived previous outbreaks. The 2021 outbreak of EVD in Guinea in particular is resurfaced by survivors of persistent infections from a large-scale outbreak at least five years ago. However, the exact "hiding place" of persistent Ebola virus and the underlying pathology of subsequent relapses or recurrent diseases of survivors — particularly those treated with standard monoclonal antibody therapy — are largely unknown. So Kevin and his team at the U.S. Army Institute for Infectious Disease Medicine used non-human primate models, the ones closest to human Ebola virus disease, to address these issues.
"Our study is the first to reveal the persistence of Ebola virus in the brain, as well as the pathology of the subsequently fatal Ebola virus-related disease in non-human primate models," Kevin explains. "We found that about 20 percent of monkeys who survived exposure to the deadly Ebola virus after treatment with monoclonal antibody therapy still had persistent Ebola infection – particularly in the ventricular system, where cerebrospinal fluid is produced, circulated and accommodated – even though Ebola has been cleared from all other organs."
Kevin specifically noted that two monkeys, who had initially recovered from Ebola-related diseases after treatment with antibody therapy, experienced a recurrence of severe clinical symptoms of Ebola infection and died of the disease. Severe inflammation and a large number of Ebola virus infections occurred in the ventricular system; no significant pathological changes and viral infections were found in other organs.
According to the authors, among human survivors of EVD, there have also been previous reports of relapses. For example, a British nurse who experienced a relapse of Ebola in the brain developed meningoencephalitis 9 months after recovering from severe EVD. She received therapeutic antibodies during the 2013-2016 Outbreak in West Africa, the largest of its kind to date. In addition, at the end of the 2018-2020 outbreak in the Democratic Republic of the Congo, a vaccinated patient who had been treated with monoclonal antibodies to EVD six months earlier recurred and died. Unfortunately, the case also led to later transmission between many people and people.
Over the past few years, Kevin's team at USAMRIID has conducted systematic studies of the persistence of Ebola virus based on non-human primate survivors. The study suggests that although the virus has been cleared from all other organs, it can hide and persist in specific areas of immunely privileged organs — such as the vitreous bodies of the eye, the seminal tubules of the testicles, and the ventricular system mentioned in this study.
"Persistent Ebola viruses may reactivate and cause the disease of survivors to recur, potentially causing new outbreaks," said Dr. Jun Liu of USAMRIID, who co-authored the paper with Dr. John C. Trefry.
Ebola is one of the deadliest known infectious diseases in humanity. It remains a major threat to Africa, with three outbreaks in Africa in 2021 alone, according to the World Health Organization. In recent years, global research efforts have led to regulatory approvals for two vaccines and two monoclonal antibody therapies to prevent and treat Ebola virus disease. These treatments are now part of standard care for infected patients.
"Fortunately, with these approved vaccines and monoclonal antibody therapies, we are in a better position to control the outbreak," Kevin added. "However, our study reinforces the need for long-term follow-up of EVD survivors – even those receiving therapeutic antibody therapy to prevent recurrence." This will help reduce the risk of disease re-emergence, while also helping to prevent patients from being further stigmatized. ”