Surviving Ebola: A historical cohort study of Ebola mortality and survival in Sierra Leone 2014-2015 - Wing et al Dec 2018

[Sly Saint]

Looks into post-viral symptoms; mentions CFS

Abstract
Background
While a number of predictors for Ebola mortality have been identified, less is known about post-viral symptoms. The identification of acute-illness predictors for post-viral symptoms could allow the selection of patients for more active follow up in the future, and those in whom early interventions may be beneficial in the long term. Studying predictors of both mortality and post-viral symptoms within a single cohort of patients could also further our understanding of the pathophysiology of survivor sequelae.

Methods/Principal findings
We performed a historical cohort study using data collected as part of routine clinical care from an Ebola Treatment Centre (ETC) in Kerry Town, Sierra Leone, in order to identify predictors of mortality and of post-viral symptoms. Variables included as potential predictors were sex, age, date of admission, first recorded viral load at the ETC and symptoms (recorded upon presentation at the ETC). Multivariable logistic regression was used to identify predictors. Of 263 Ebola-confirmed patients admitted between November 2014 and March 2015, 151 (57%) survived to ETC discharge. Viral load was the strongest predictor of mortality (adjusted OR comparing high with low viral load: 84.97, 95% CI 30.87–345.94). We did not find evidence that a high viral load predicted post-viral symptoms (ocular: 1.17, 95% CI 0.35–3.97; musculoskeletal: 1.07, 95% CI 0.28–4.08). Ocular post-viral symptoms were more common in females (2.31, 95% CI 0.98–5.43) and in those who had experienced hiccups during the acute phase (4.73, 95% CI 0.90–24.73).

Conclusions/Significance
These findings may add epidemiological support to the hypothesis that post-viral symptoms have an immune-mediated aspect and may not only be a consequence of high viral load and disease severity.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209655

One hypothesis for the underlying cause of EVD post-viral symptoms is persistence of the virus within immune privileged sites[38], which is more likely in patients with high viral load and severe, prolonged disease[39,40]. An alternative (but not necessarily exclusive) theory is based upon the observation that EBOV infection results in substantial immune activation[40], and that it is this that causes the observed post-viral symptoms[8].

Our findings are more consistent with the latter theory: we found that viral load on admission was not predictive of post-viral symptoms. The suggestion of greater risk of ocular sequelae among women is in line with gender imbalances in a number of immuno-inflammatory conditions (including chronic fatigue syndrome/myalgic encephalopathy, rheumatoid arthritis, and multiple sclerosis)[41,42], and emerging understanding of the impact of sex on immune function during viral infection[43].

The similarity of some post-EVD sequelae to the symptoms of chronic fatigue syndrome has been noted previously, and suggestions have been made that Ebola survivors could be managed by approaches similar to those used for chronic fatigue syndrome or alternatively treated prophylactically with disease-modifying anti-rheumatic drugs (e.g. sulfasazine)[7,44–46]. Furthermore, insatiable hunger, weight loss, palpitations and fever are symptoms of hyperthyroidism, while hair loss, memory loss, low mood, arthralgia and amenorrhoea are symptoms of hypothyroidism (with eye problems symptomatic of both conditions). Since animal models of EBOV infection have demonstrated thyroiditis, further evaluation of thyroid function in survivors is warranted[47].

 

[obeat]

http://www.jimmunol.org/content/198/5/1782
This paper was referenced in the above. It explains the different immune response in females and males to viral infections and to vaccination. Females have stronger immune responses. Very detailed.

 

[Peter T]

An interesting article.

However I have no specific recollection of having had hiccups during my acute glandular fever stage leading to my ME.

 

[Hutan]

Great to see studies being done of Ebola survivors. There should be more.

As evidence accumulates from different study sites, we believe that a systematic review and meta-analysis of post-viral symptoms and their predictors would be worthwhile, as would pooled analysis: the latter, in particular, would resolve possible issues with low study power. Such summary analyses, however, would benefit from standardised case definitions of health problems being studied and time criteria, e.g. for what constitutes the acute and post-viral phases. It will also be essential to include a population control group as many of the symptoms may be common in the general population as well.

This study didn't ask patients at survivor clinics about fatigue, muscle fatiguability, dizziness or PEM and only started asking about headaches part of the way through when it became clear that many people had headaches. Given the understanding that the post-Ebola syndrome could be ME/CFS, it would be good to see studies screening for more typical ME/CFS symptoms.

Perhaps the larger ME/CFS organisations could push for a more coordinated approach to post-Ebola studies? Maybe this is something that IAFME could do when chatting with the WHO in Geneva? @Action for M.E. Or a role for the UK CMRC? @Chris Ponting

 

[Starlight]

I hope they don't start to manage them as they manage ME patients. That wouldn't bring them any joy or improvement.

 

[Daisybell]

I hope they don't start to manage them as they manage ME patients. That wouldn't bring them any joy or improvement.

But maybe, just maybe, it might change how ME is perceived.....?

 

[Esther12]

I had been wondering if researchers looking at the ebola aftermath might turn up things that might relate to to ME/CFS.

I hope they don't start to manage them as they manage ME patients. That wouldn't bring them any joy or improvement.

I didn't see a reference to CBT/GET. Maybe there's a growing awareness of the problems with these approaches?

 

[Hutan]

I didn't see a reference to CBT/GET. Maybe there's a growing awareness of the problems with these approaches?

Well, there was this:

The similarity of some post-EVD sequelae to the symptoms of chronic fatigue syndrome has been noted previously, and suggestions have been made that Ebola survivors could be managed by approaches similar to those used for chronic fatigue syndrome or alternatively treated prophylactically with disease-modifying anti-rheumatic drugs (e.g. sulfasazine)

Not sure which approaches they are thinking of, the ones that come immediately to mind are 1. suggesting that they are hysterical/stressed/need to think more positively about life and hoping they go away; 2. CBT; 3. GET.

Interesting about the suggestion of anti-rheumatic drugs as a suggestion for treatment of post-Ebola syndrome. I haven't heard anything about that before.

 

[Esther12]

Well, there was this:

The references for that were [7,44–46], which didn't look to be promoting CBT/GET... I'm not sure about the coenzyme Q10 stuff either though:

7) Scott JT, Semple MG. Ebola virus disease sequelae: a challenge that is not going away [Internet]. The Lancet Infectious Diseases. 2017. pp. 470–471. pmid:28094207

44. Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett. 2009;30: 470–6. Available: http://www.ncbi.nlm.nih.gov/pubmed/20010505 pmid:20010505

45. Abdollahzad H, Aghdashi MA, Asghari Jafarabadi M, Alipour B. Effects of Coenzyme Q10 Supplementation on Inflammatory Cytokines (TNF-α, IL-6) and Oxidative Stress in Rheumatoid Arthritis Patients: A Randomized Controlled Trial. Arch Med Res. 2015;46: 527–533. pmid:26342738

46. Castro-Marrero J, Sáez-Francàs N, Segundo MJ, Calvo N, Faro M, Aliste L, et al. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome–A randomized, controlled, double-blind trial. Clin Nutr. 2016;35: 826–834. pmid:26212172

 

[rvallee]

I had been wondering if researchers looking at the ebola aftermath might turn up things that might relate to to ME/CFS.



I didn't see a reference to CBT/GET. Maybe there's a growing awareness of the problems with these approaches?

I do see more and more comments on Twitter over time, growing concerns that maybe going all in with CBT for every ill and condition was a bad idea and that the evidence base may actually be fragile and possibly misleading.

Far from a tipping point but I'd say frequency has increased from anecdotal sightings, in large part because of concerns about similar failures with some psychiatric conditions and the crisis of replicability. This entire body of work is built on the lowest possible tier of research quality and high bias, so it's a natural target for concerns, especially when it is usually implemented as an alternative to actual medicine. If it was complementary it would have had a longer shelf life, but as a primary treatment the field has jumped several steps and made claims that cannot stand scrutiny.

I think that ultimately it will all end up as a shameful embarrassment that will be forgotten in archives, but it's still a long way to go, unfortunately.