Dr Janet Scott is a clinical lecturer in infectious diseases at the MRC-University of Glasgow Centre for Virus Research. In late 2015, she was deployed to Liberia to lead a clinical trial of an antiviral drug for Ebola. Afterwards, she moved to Sierra Leone to investigate whether the antibody-rich, yellowish liquid part of blood, called plasma, drawn from Ebola survivors could benefit those currently fighting the disease. During this work, Dr Scott became involved in the clinical care of these survivors who suffer from ongoing health problems, even after the virus had been cleared from their bodies – a subject she continues to research today.
How did you start working with Ebola survivors?
Talking to Ebola survivors, it became evident that they were having real difficulty accessing health care. They were absolutely desperate, because they were suffering a lot of consequences of having had Ebola, but because of the stigma associated with it, they were being turned away from their normal health care providers. People were not comfortable treating them, because they were concerned that they might still be able to transmit Ebola.
Working with the survivors and the local Sierra Leonean doctors, I helped the patients form a self-support network, called the Survivors’ Association, and we set up a follow-up clinic, which was inspired by ‘one-stop’ breast cancer clinics in the UK. Rather than going to lots of different appointments, patients could access many things such as a clinical assessment, counselling, physiotherapy and contact with the Survivors Association on a single day. The clinic also provided a platform for us to study the consequences of past Ebola infection on people’s health – or post-Ebola syndrome, as we called it – which provided us with further knowledge about what kinds of things our survivors needed. Eventually, we were able to open up the service to other Ebola survivors in Freetown, the capital of Sierra Leone. By the time I left the project in 2017, we had 500 Ebola survivors signed up to the survivor's clinic, which is 10% of all of the survivors in Sierra Leone.
What sorts of symptoms were they suffering from?
There are lots of symptoms and they vary in severity, but almost all of them have something. There are very few people who come out the other side of Ebola and say, "actually, I'm fine." Even so, there are three major groups of things which really say ‘post-Ebola syndrome’ to me. These are visual problems, musculoskeletal pain and headaches. Fatigue is also in there, but Ebola survivors complain more about pain than they do about fatigue, which is different to COVID. Some of that could be about language and culture and the way you express the same thing, or it could be differences between what happens after Ebola and COVID.
With my colleague Paul Steptoe from the St Paul’s Eye Department in Liverpool, we also set up an ophthalmology clinic, because many of the survivors were suffering from eye problems - they get white cataracts and uveitis (inflammation of the middle layer of the eye, which causes pain and visual problems). Some of them also get this very specific, sharp diamond-shaped lesion in the retina, which is only found in Ebola survivors, and which may indicate that the virus travels through neurons.
How prevalent is post-Ebola syndrome?
We did a study looking at overall disability levels after one year, and found that 78% of all survivors had some level of disability, compared to 11% of their close contacts. There are also some papers from central African cohorts of patients, suggesting that some of them were still experiencing symptoms after twenty-plus years.
Can any of these symptoms be treated?
So long as there aren’t other serious eye problems, you can do a cataract operation and restore people’s vision. But some of the other stuff - the fatigue; the musculoskeletal pain, which is really major; and the headaches, which are also not trivial – we are not so clear about their underlying cause. We had a neurologist examine some of the survivors with headaches, and the closest you could come to describing them is as migraine headaches. And of course, nobody really knows what causes migraines, so that didn’t get us much further forward, except for us to try migraine-style therapies on them.
Some people do respond to paracetamol and ibuprofen, but on the other hand, you’ve got people who are not able to work, people who are not able to walk, mothers who are not able to pick up their children, some really very debilitating symptoms.
Do you have any insights into what’s causing these symptoms?
There are two main ideas. One is that it’s a consequence of an inflammatory response, which continues after the infection ends, and the other is persistent virus. We know that a certain proportion of Ebola survivors have persistent virus in immuno-privileged sites, such as the prostate gland. This has mostly been measured in men – Ebola virus is sometimes found in their semen. So, it could be that there is niggling persistent infection in these immuno-privileged sites that keeps the post-Ebola syndrome going.
Could there be any similarities with ‘long COVID’?
There could be an overlap: both of them are post-viral syndromes, but they’re also distinct from each other. Although COVID is a multi-organ disease, it is principally a respiratory virus, and people are suffering from respiratory sequalae. So, I didn't see a lot of breathlessness in Ebola survivors. It did happen, but mostly in the first few weeks after leaving the treatment unit – and I suspect that was to do with the chlorine which was used to clean the units.
We sometimes saw pulmonary embolisms (blockages in the arteries carrying blood to the lungs) post-Ebola, which you can also get with COVID-19 – probably because both infections cause inflammation (and inflammation can trigger blood clots), but the Ebola survivors weren't getting long-term lung fibroses (scarring) in the way that we're seeing it reported for COVID-19. I certainly think it's worth doing a comparison between the two diseases, to look at where the similarities and the differences lie.
Is there anything you think those doctors treating patients with long COVID could learn from Ebola?
First of all, it's about taking it seriously. That this is something real, that a good proportion of people don't get over it just by sitting at home and resting up for a bit. I would have liked to have seen a more active treatment programme for Ebola survivors, and I'm really glad to see that's now occurring for people recovering from COVID. The other thing is to keep an open mind about it: normally, the sorts of viruses that go latent (dormant) are DNA viruses like herpes simplex virus, which replicate in the nucleus of cells (and can integrate their DNA into the DNA of their host). Ebola is an RNA virus, which replicates in the cytoplasm, and this should make it more clearable. And yet, here are people with persistent symptoms. It’s the same with COVID (which is another RNA virus). It shouldn’t be persistent. So, my top hypothesis for what’s happening with long COVID is that it’s a post-viral syndrome, meaning you've had the virus and cleared it, but you're still suffering from the consequences of having had the virus, rather than you've got the virus and it hasn't gone away yet.