Tag: post-viral fatigue syndrome

Systems-level temporal immune-metabolic profile in Crimean-Congo hemorrhagic fever virus infection

Abstract:

Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2).

The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection.

The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4+ and CD8+ T cells, CD14+ monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.

Source: Ambikan AT, Elaldi N, Svensson-Akusjärvi S, Bagci B, Pektas AN, Hewson R, Bagci G, Arasli M, Appelberg S, Mardinoglu A, Sood V, Végvári Á, Benfeitas R, Gupta S, Cetin I, Mirazimi A, Neogi U. Systems-level temporal immune-metabolic profile in Crimean-Congo hemorrhagic fever virus infection. Proc Natl Acad Sci U S A. 2023 Sep 12;120(37):e2304722120. doi: 10.1073/pnas.2304722120. Epub 2023 Sep 5. PMID: 37669378; PMCID: PMC10500270. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500270/ (Full text)

An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond)

Abstract:

Objectives: Some people do not fully recover from an acute viral infection and experience persistent symptoms or incomplete recovery for months or even years. This is not unique to the SARS-CoV-2 virus and history shows that post-viral conditions like post COVID-19 condition, also referred to as Long Covid, are not new. In particular, during and after pandemics caused by respiratory viruses in which large parts of the population were infected or exposed, professional and public attention was increased, not least because of the large number of people affected.

Methods: Given the current relevance of the topic, this article aims to narratively review and summarize the literature on post-viral symptoms during past pandemics and to supplement and illustrate it with Swiss examples from the pandemics of 1890, 1918–1920 and later.

Results: Post-viral diseases were an increasingly emphasised health topic during and after past pandemics triggered by respiratory infections over the last 150 years.

Conclusion: In the next pandemic, it should not be surprising that post-viral conditions will again play a role, and pandemic plans should reflect this.

Source: Staub, Kaspar; Ballouz, Tala; Puhan, Milo (2024). An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond). Public Health Reviews, 45:1606966. https://www.ssph-journal.org/articles/10.3389/phrs.2024.1606966/full (Full text)

How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review

Abstract:

Background: Post Coronavirus disease (COVID) and other post-viral infection syndromes present an overlap of pathogenesis, onset, progression, and symptom profile. We aimed to systematically describe studies on post-viral conditions and determine the entity of post COVID compared to other post-viral conditions in children.

Methods: We conducted a systematic search of the Embase, MEDLINE, Cochrane Library, and GoogleScholar databases (January 1946-3 November 2023), according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The main outcomes were differences in condition duration, symptom type, and development of chronic symptoms. This systematic review was registered on PROSPERO (CRD42023401789).

Findings: 35/5051 studies were included, with 42,934 children, adolescents and young adults (0-20 years old) overall. Twenty-eight studies focused on post COVID symptoms, followed by five papers on Respiratory Syncytial Virus (RSV) and Rhinovirus, one study on Epstein-Barr Virus (EBV), and one on gastrointestinal viruses. Studies on post COVID mainly reported data on older children/adolescents, describing long-lasting symptoms, including fatigue, neurologic, cardiorespiratory, musculoskeletal, mental health, and gastrointestinal symptoms. The maximum described symptoms duration was eighteen months, with an average follow-up of seven months. The development of chronic symptoms was reported by 30 studies (93.8%) for 10,473/28,474 patients (36.8%). Recovery was achieved in 18,001/28,474 cases (63.2%). The study on EBV reported persistent fatigue in adolescents for a similar duration (6 months, 46% chronic). Studies on RSV and Rhinovirus were mainly done in children under three years, with development of recurrent wheezing (up to 3 years).

Interpretation: Post-viral fatigue was a shared feature between post COVID and post EBV conditions. A better understanding of post COVID as a unique condition, sharing features with other post-viral syndromes, is needed. The healthcare burden and socio-economic consequences for children and their families warrant further investigation and development of appropriate healthcare management plans. The foremost requirement is the establishment of consistent and shareable definitions, as well as a consensus on outcomes, to effectively evaluate follow-up and quantify the burden of different viral infections.

Source: Minotti C, McKenzie C, Dewandel I, Bekker C, Sturniolo G, Doni D, Giaquinto C, Van Der Zalm MM, Donà D. How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review. EClinicalMedicine. 2024 Feb 2;68:102436. doi: 10.1016/j.eclinm.2024.102436. PMID: 38333536; PMCID: PMC10850405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10850405/ (Full text)

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

Abstract:

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders.
Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.
Source: Mantle D, Hargreaves IP, Domingo JC, Castro-Marrero J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. International Journal of Molecular Sciences. 2024; 25(1):574. https://doi.org/10.3390/ijms25010574 https://www.mdpi.com/1422-0067/25/1/574 (Full text)

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

Abstract:

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown cause characterized by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently post-COVID-19 condition (Long COVID).

To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders.

Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. Accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and Long COVID.

To address this issue, this article aimed to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Source: Mantle, D.; Hargreaves, I.P.; Domingo, J.C.; Castro-Marrero, J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. Preprints 2023, 2023111554. https://doi.org/10.20944/preprints202311.1554.v1 https://www.preprints.org/manuscript/202311.1554/v1 (Full text available as PDF file)

Post Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current knowledge and Future Directions

Abstract:

Post-viral pain syndrome, also known as post-viral syndrome (PVS), is a complex condition characterized by persistent pain, fatigue, musculoskeletal pain, neuropathic pain, neurocognitive difficulties, and sleep disturbances1,2 that can occur after an individual has recovered from a viral infection. Much remains unknown regarding the pathophysiology of post-viral syndromes and few studies have provided a comprehensive summary of the condition, agents that cause it, and successful treatment modalities.

With the COVID-19 pandemic continuing to affect millions of people worldwide, the need for understanding the etiology of post-viral illness and how to help individuals cope with the sequalae is paramount.2 This narrative review provides a summary of the sequelae of post-viral syndromes, viral agents that cause it, the pathophysiology, treatment, and future considerations for research and targeted therapies.

Source: Caleb Tackey, P. Maxwell Slepian, Hance Clarke & Nimish Mittal (2023) Post Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current knowledge and Future Directions, Canadian Journal of Pain, DOI: 10.1080/24740527.2023.2272999 https://www.tandfonline.com/doi/full/10.1080/24740527.2023.2272999 (Full text)

Fatigue presentation, severity, and related outcomes in a prospective cohort following post-COVID-19 hospitalization in British Columbia, Canada

Abstract:

Introduction: Increasing evidence on long-term health outcomes following SARS CoV-2 infection shows post-viral symptoms can persist for months. These symptoms are often consistent with those of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS). The aim of the present study was to examine the prevalence and outcome predictors of post-viral fatigue and related symptoms 3- and 6-months following symptom onset.

Methods: A prospective cohort of patients hospitalized with Coronavirus disease (COVID-19) (n = 88) were recruited from a Post-COVID-19 Respiratory Clinic (PCRC) in Vancouver, Canada to examine predictors of long-term fatigue and substantial fatigue. Multivariable mixed effects analyses examined the relationship between patient predictors, including pre-existing comorbidities, patient reported outcome measures, and fatigue and substantial fatigue at follow-up.

Results: The number of patients experiencing fatigue or substantial fatigue at 3 months post-infection were 58 (67%) and 14 (16%) respectively. At 6 months these numbers declined to 47 (60%) patients experiencing fatigue and 6 (6%) experiencing substantial fatigue. Adjusted analysis, for sex, age, and time, revealed the number of pre-existing comorbidities to be associated with fatigue (OR 2.21; 95% CI 1.09-4.49; 0.028) and substantial fatigue (OR 1.73; 95% CI 1.06-2.95; 0.033) at 3 months follow-up. Except for shortness of breath, self-care, and follow-up time, all follow-up variables were found to be associated with fatigue and substantial fatigue at 3 months.

Conclusion: Fatigue and substantial fatigue are common after COVID-19 infection but often diminish over time. A significant number of patients continue to exhibit long-term fatigue at 6 months follow-up. Further research is needed to clarify the causality of viral infections in the development and severity of fatigue as a symptom and in meeting post-viral fatigue syndrome or ME/CFS diagnostic criteria.

Source: Magel T, Meagher E, Boulter T, Albert A, Tsai M, Muñoz C, Carlsten C, Johnston J, Wong AW, Shah A, Ryerson C, Mckay RJ, Nacul L. Fatigue presentation, severity, and related outcomes in a prospective cohort following post-COVID-19 hospitalization in British Columbia, Canada. Front Med (Lausanne). 2023 Jun 29;10:1179783. doi: 10.3389/fmed.2023.1179783. PMID: 37457578; PMCID: PMC10344448. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344448/ (Full text)

Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis

Abstract:

Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19’s long-term effects at 12 months and above.

We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976.

At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.

Source: Mudgal S K, Gaur R, Rulaniya S, et al. (March 18, 2023) Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis. Cureus 15(3): e36325. doi:10.7759/cureus.36325 https://www.cureus.com/articles/143288-pooled-prevalence-of-long-covid-19-symptoms-at-12-months-and-above-follow-up-period-a-systematic-review-and-meta-analysis#!/ (Full text)

Post-Viral Fatigue Following SARS-CoV-2 Infection during Pregnancy: A Longitudinal Comparative Study

Abstract:

Studies reported post-COVID-19 fatigue in the general population, but not among pregnant women. Our objectives were to determine prevalence, duration, and risk factors of post-viral fatigue among pregnant women with SARS-CoV-2.

This study involved 588 pregnant women with SARS-CoV-2 during pregnancy or delivery in Brazil. Three groups were investigated: G1 (n = 259, symptomatic infection during pregnancy); G2 (n = 131, positive serology at delivery); G3 (n = 198, negative serology at delivery). We applied questionnaires investigating fatigue at determined timepoints after infection for G1, and after delivery for all groups; fatigue prevalence was then determined.

Cox regression was used to estimate hazard ratio (HR) and 95% CI of the risk of remaining with fatigue in G1. Overall fatigue prevalence in G1 at six weeks, three months and six months were 40.6%, 33.6%, and 27.8%, respectively. Cumulative risk of remaining with fatigue increased over time, with HR of 1.69 (95% CI: 0.89-3.20) and 2.43 (95% CI: 1.49-3.95) for women with moderate and severe symptoms, respectively.

Multivariate analysis showed cough and myalgia as independent risk factors in G1. Fatigue prevalence was significantly higher in G1 compared to G2 and G3. Post-viral fatigue prevalence is higher in women infected during pregnancy; fatigue’s risk and duration increased with the severity of infection.

Source: Oliveira AMDSS, Carvalho MA, Nacul L, Cabar FR, Fabri AW, Peres SV, Zaccara TA, O’Boyle S, Alexander N, Takiuti NH, Mayaud P, Brizot ML, Francisco RPV. Post-Viral Fatigue Following SARS-CoV-2 Infection during Pregnancy: A Longitudinal Comparative Study. Int J Environ Res Public Health. 2022 Nov 26;19(23):15735. doi: 10.3390/ijerph192315735. PMID: 36497810; PMCID: PMC9737157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737157/ (Full text)

Is SARS-CoV-2 the only cause of long-COVID?

Abstract:

Around 10% of adults infected with SARS-CoV-2 that survive a first episode of COVID-19 appear to experience long-term clinical manifestations. The signs and symptoms of this post-acute COVID-19 syndrome (PACS) include fatigue, dyspnea, joint pain, myalgia, chest pain, cough, anosmia, dysgeusia, headache, depression, anxiety, memory loss, concentration difficulties, and insomnia. These sequelae remind the constellation of clinical manifestations previously recognized as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS).

This condition has been described following distinct infectious events, mostly acute viral illnesses. In this way, the pathophysiology of PACS might overlap with mechanisms involved in other post-infectious fatigue syndromes. The risk of PACS is more frequent in women than men. Additional host genetic factors could be involved.

There is a dysregulation of multiple body organs and systems, involving the immune system, the coagulation cascade, endocrine organs, autonomic nervous system, microbiota-gut-brain axis, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, etc. Hypothetically, an abnormal response to certain infectious agents could trigger the development of postinfectious fatigue syndromes.

Source: Pintos-Pascual I, Moreno-Torres V, Ibánez-Estéllez F, Corrales-Rodriguez P, Treviño A, Corpas M, Corral O, Soriano V, de Mendoza C. Is SARS-CoV-2 the only cause of long-COVID? AIDS Rev. 2022 Nov 25. doi: 10.24875/AIDSRev.22000025. Epub ahead of print. PMID: 36427058.  https://pubmed.ncbi.nlm.nih.gov/36427058/