Post-Ebola Symptoms 7 Years After Infection: The Natural History of Long Ebola, 2022, Wohl et al

Long Ebola . . .

Abstract
Background
Lingering symptoms have been reported by survivors of Ebola virus disease (EVD). There are few data describing the persistence and severity of these symptoms over time.

Methods
Symptoms of headache, fatigue, joint pain, muscle pain, hearing loss, visual loss, numbness of hands or feet were longitudinally assessed among participants in the Liberian Ebola Survivors Cohort study. Generalized linear mixed effects models, adjusted for sex and age, were used to calculate the odds of reporting a symptom and it being rated as highly interfering with life.

Results
From June 2015 to June 2016, 326 survivors were enrolled a median of 389 days (range 51–614) from acute EVD. At baseline 75.2% reported at least 1 symptom; 85.8% were highly interfering with life. Over a median follow-up of 5.9 years, reporting of any symptom declined (odds ratio for each 90 days of follow-up = 0.96, 95% confidence interval [CI]: .95, .97; P < .0001) with all symptoms declining except for numbness of hands or feet. Rating of any symptom as highly interfering decreased over time. Among 311 with 5 years of follow-up, 52% (n = 161) reported a symptom and 29% (n = 47) of these as highly interfering with their lives.

Conclusions
Major post-EVD symptoms are common early during convalescence and decline over time along with severity. However, even 5 years after acute infection, a majority continue to have symptoms and, for many, these continue to greatly impact their lives. These findings call for investigations to identify the mechanisms of post-EVD sequelae and therapeutic interventions to benefit the thousands of effected EVD survivors.

https://academic.oup.com/cid/article-abstract/76/3/e835/6692535?redirectedFrom=fulltext

 

From reading papers, it appears that post Ebola syndromes don't mention autonomic dysfunction or POTS.

Wouldn't that be an indicator that they don't experience PEM?

 

My guess would be addressing the encephalomyelitis part.

 

This study was published in 2019

Long-term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation; Sam Tozay, William A Fischer, II, David A Wohl, Kayla Kilpatrick, Fei Zou, Edwina Reeves, Korto Pewu, Jean DeMarco, Amy James Loftis, Katie King

https://academic.oup.com/cid/article/71/7/1749/5613876?login=false

Abstract
Background
Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola virus disease (EVD) survivors. However, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms.

Methods
The presence and patterns of 8 cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors who participated in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation.

Results
At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least 1 new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors, with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache, while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up.

Conclusions
Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.

 

The prevalence of Post-Ebola Syndrome hearing loss, Sierre Leone

LINK

 

Fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease in Democratic Republic of the Congo: a case study, 2024, Daniel Mukadi-Bamuleka et al

 

So sad.

 

Advancing mechanistic understanding of post-acute sequelae of Ebola virus disease

We read with great interest the Article published in The Lancet Microbe by Mosoka P Fallah and colleagues,1 which investigated inflammatory pathways in post-acute sequelae of Ebola virus disease (PASE) using data of the PREVAIL III cohort.

The study provided important insights regarding mechanisms underlying the heterogeneity of PASE through an innovative hierarchical design and multi-marker analysis. Although a unique subgroup analysis in the study1 revealed distinct biological pathways associated with PASE, several aspects warrant further consideration to enhance mechanistic understanding.

First, the selected 25-marker panel, although derived from literature on HIV and COVID-19, inadequately captures Ebola-specific immune dysregulation patterns. Additionally, the acute-phase immunological correlates of disease severity, particularly markers indicative of T-cell over-activation or exhaustion, warrant inclusion in the panel because of their established prognostic value in the progression of Ebola virus disease.2

Two studies3,4 on post-acute sequelae of SARS-CoV-2 infection (also known as long COVID) reported persistently elevated levels of soluble co-inhibitory receptors such as TIM-3 and PD-1 in long-term sequelae, reflecting T-cell exhaustion patterns observed in both acute SARS-CoV-2 infection and Ebola virus disease. Even though the dynamics of soluble PD-1 and CTLA-4 remain uncharacterised in PASE, the mechanistic relevance of the markers to viral persistence and chronic inflammation necessitates systematic evaluation. Expanding the biomarker panel to include soluble immune checkpoints would facilitate a comprehensive mapping of immune dysregulation in the pathogenesis of PASE.

Second, the exclusion of female survivors from the viral shedding subgroup analyses in the study1 overlooks potential sex-specific immunological differences. Although no relevant reports have addressed sex-based differences in the incidence of PASE, accumulating evidence on long COVID suggests a female predisposition to post-acute sequelae, with notable sex-based variations in clinical manifestations (eg, fatigue and headache) and immune regulation.5,6 Male-specific analyses of semen viral shedding are valuable; however, they limit a comprehensive evaluation of sex as a biological variable in PASE pathogenesis. Future studies should prioritise sex-based analyses using alternative viral shedding measures to elucidate the complex relationship between inflammatory markers and PASE.

In conclusion, Fallah and colleagues provide compelling evidence of the heterogeneity in inflammatory pathways in PASE, demonstrating that different profiles of inflammatory markers reflect distinct biological mechanisms that drive post-acute sequelae. Future investigations should incorporate Ebola-specific soluble immune checkpoints and implement sex-based analyses to achieve a comprehensive understanding of the immune landscape of PASE.

 

This is the article they're referring to:

Associations of inflammatory markers with post-acute clinical findings among survivors of Ebola virus disease with and without viral RNA shedding in the semen in Liberia: a nested case-control study