Tag: 2022

Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study

Abstract:

Objectives: Primary objective: to determine the point prevalence and incidence rate of severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children aged 5-16 years over 13 months.

Secondary objectives: to describe the demographic features, symptoms, impact on activities of daily living, school attendance and time to diagnosis.

Design: Prospective surveillance study conducted by the British Paediatric Surveillance Unit. Paediatricians was asked if they had assessed a child with severe ME/CFS (screening definition for prevalence and incidence: children (5-16 years) diagnosed with ME/CFS so severe that they are unable to attend school for more than 1 hour a week during the last 6 weeks of the school term).

Participants: Patients 5-16 years of age, seen by paediatricians and two large ME/CFS specialist services across the UK and Ireland.

Outcome measures: Paediatrician-completed questionnaires describing demographics, symptoms, function and treatment, (applying National Institute for Health and Care Excellence (NICE)-recommended criteria to assess severity of ME/CFS). Diagnosis of severe, probable severe or possible severe ME/CFS was made only with evidence of NICE-recommended screening blood tests.

Results: 285 cases were reported, of which of which 33 were severe, 4 probable severe and 55 possible severe. Estimated prevalence was 3.2 per million children (95% CI 2.2 to 4.5). Including possible/probable severe ME/CFS gave 8.9 per million children (95% CI 7.2 to 11). The incidence rate was 0.90 per million children-years (95% CI 0.43 to 1.65) (1.97 per million children-years (95% CI 1.24 to 2.99)). Median age was 13 years and 58% of cases were female. Median time to diagnosis was 0.47 years.

Conclusions: Although the incidence of children presenting with severe ME/CFS is low, all were very disabled. In addition, the majority receive little or no education. Paediatricians need to consider how to provide rehabilitation and education for these disabled young people.

Source: Royston AP, Rai M, Brigden A, Burge S, Segal TY, Crawley EM. Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study. Arch Dis Child. 2022 Dec 1:archdischild-2022-324319. doi: 10.1136/archdischild-2022-324319. Epub ahead of print. PMID: 36456114. https://adc.bmj.com/content/early/2022/11/30/archdischild-2022-324319 (Full text)

Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls.

Methods: Six female patients with ME/CFS and six age, BMI and sex matched controls underwent 23Na-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content.

Results: Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R2 = 0.3832).

Conclusion: Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.

Source: Petter E, Scheibenbogen C, Linz P, Stehning C, Wirth K, Kuehne T, Kelm M. Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Transl Med. 2022 Dec 9;20(1):580. doi: 10.1186/s12967-022-03616-z. PMID: 36494667. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03616-z (Full text)

Mild SARS-CoV-2 infection results in long-lasting microbiota instability

Abstract:

Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of SARS-CoV-2 infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting. To address this knowledge gap, we longitudinally sampled 14 SARS-CoV-2 positive subjects who remained outpatient and 4 household controls. SARS-CoV-2 cases exhibited a significantly less stable gut microbiota relative to controls, as long as 154 days after their positive test. These results were confirmed and extended in the K18-hACE2 mouse model, which is susceptible to SARS-CoV-2 infection. All of the tested SARS-CoV-2 variants significantly disrupted the mouse gut microbiota, including USA-WA1/2020 (the original variant detected in the United States), Delta, and Omicron. Surprisingly, despite the fact that the Omicron variant caused the least severe symptoms in mice, it destabilized the gut microbiota and led to a significant depletion in Akkermansia muciniphila. Furthermore, exposure of wild-type C57BL/6J mice to SARS-CoV-2 disrupted the gut microbiota in the absence of severe lung pathology.

IMPORTANCE Taken together, our results demonstrate that even mild cases of SARS-CoV-2 can disrupt gut microbial ecology. Our findings in non-hospitalized individuals are consistent with studies of hospitalized patients, in that reproducible shifts in gut microbial taxonomic abundance in response to SARS-CoV-2 have been difficult to identify. Instead, we report a long-lasting instability in the gut microbiota. Surprisingly, our mouse experiments revealed an impact of the Omicron variant, despite producing the least severe symptoms in genetically susceptible mice, suggesting that despite the continued evolution of SARS-CoV-2 it has retained its ability to perturb the intestinal mucosa. These results will hopefully renew efforts to study the mechanisms through which Omicron and future SARS-CoV-2 variants alter gastrointestinal physiology, while also considering the potentially broad consequences of SARS-CoV-2-induced microbiota instability for host health and disease.

Source: Vaibhav Upadhyay, Rahul Suryawanshi, Preston Tasoff, Maria McCavitt-Malvido, G. Renuka Kumar, Victoria Wong Murray, Cecilia Noecker, Jordan E. Bisanz, Yulin Hswen, Connie Ha, Bharat Sreekumar, Irene P. Chen, Susan V Lynch, Melanie Ott, Sulggi Lee, Peter J. Turnbaugh. Mild SARS-CoV-2 infection results in long-lasting microbiota instability. bioRxiv 2022.12.07.519508; doi: https://doi.org/10.1101/2022.12.07.519508  https://www.biorxiv.org/content/10.1101/2022.12.07.519508v1.full (Full text)

Investigating undergraduate medical education on myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background and Objectives: ME/CFS is a poorly understood, highly stigmatised condition which significantly reduces patients’ quality of life. ME/CFS had been identified as a gap in many health professionals’ knowledge, therefore this research aims to explore the understanding of ME/CFS amongst UK medical students.

Methods: An online survey developed using Redcap was distributed to participants who were recruited via social media or via medical societies’ emails. The participants were undergraduate UK medical students.

Results: 94 students completed the survey from more than 16 medical schools. 35% of the students did not know what ME/CFS is and 88% say that the disease has not been covered in their course so far. 89% of participants would like to learn more about ME/CFS, specifically through elearning and videos.

Discussion: Participants were generally unaware of ME/CFS and its symptoms and had not received relevant teaching or exposure to the disease. Education on ME/CFS within undergraduate UK medical schools is currently inadequate and the interest expressed by students in this survey demonstrates a new teaching opportunity for UK medical schools.

Source: Victoria Alice Reid and Nina Muirhead.Investigating undergraduate medical education on myalgic encephalomyelitis/chronic fatigue syndrome. The British Student Doctor Journal (BSDJ), Cardiff University Press, Year: 2022, Volume: 6 Issue: 1, Page/Article: 35-40. https://thebsdj.cardiffuniversitypress.org/articles/308 (Full text available as PDF file)

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor?

Objective: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition.

Methods: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated.

Results: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue.

Conclusions: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Source: Azcue N, Gómez-Esteban JC, Acera M, Tijero B, Fernandez T, Ayo-Mentxakatorre N, Pérez-Concha T, Murueta-Goyena A, Lafuente JV, Prada Á, López de Munain A, Ruiz-Irastorza G, Ribacoba L, Gabilondo I, Del Pino R. Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder? J Transl Med. 2022 Dec 6;20(1):569. doi: 10.1186/s12967-022-03764-2. PMID: 36474290. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03764-2 (Full text)

Impaired pulmonary and muscle function during moderate exercise in female patients recovered from SARS-CoV-2

Abstract:

This study aimed to assess pulmonary and muscle dysfunction by analyzing the slow component of oxygen uptake (VO2SC), and mechanical and ventilatory efficiency in adult women recovered from the severe acute respiratory syndrome coronavirus type II (SARS-CoV-2) during a constant load test. 32 women (N = 17 patients with SARS-CoV-2; N = 15 control group) performed two cardiopulmonary exercise tests (CPX) on a cycle ergometer.

In the first test, the participants performed incremental CPX until extenuation. In the second test the participants performed a 10-min CPX at a constant load intensity (watts) corresponding to the first ventilatory threshold. There was a 48-72 h rest period between the two tests. There was a significant increase in the VO2SC in the patients recovered from SARS-CoV-2 (160.4 ± 60 mL min-1) in comparison with the healthy participants (59.6 ± 65 mL min-1) (P < 0.001).

Mechanical efficiency significantly decreased in patients recovered from SARS-CoV-2 compared to the control group (P = 0.04). Ventilatory inefficiency significantly increased in the patients recovered from SARS-CoV-2 compared with the control group (P < 0.001). Adult women recovered from SARS-CoV-2 infection have important pulmonary and muscular dysfunction and fatigue which contributes to increasing the VO2SC and reducing mechanical and ventilatory efficiency during mild-moderate exercise at a constant load.

Source: Pleguezuelos E, Del Carmen A, Moreno E, Ortega P, Robles A, Serra-Prat M, Miravitlles M, Yebenes JC, Garnacho-Castaño MV. Impaired pulmonary and muscle function during moderate exercise in female patients recovered from SARS-CoV-2. Sci Rep. 2022 Dec 4;12(1):20943. doi: 10.1038/s41598-022-24941-9. PMID: 36464697.  https://www.nature.com/articles/s41598-022-24941-9 (Full text)

Tissue specific signature of HHV-6 infection in ME/CFS

Abstract:

First exposure to various human herpesviruses (HHVs) including HHV-6, HCMV and EBV does not cause a life-threatening disease. In fact, most individuals are frequently unaware of their first exposure to such pathogens. These herpesviruses acquire lifelong latency in the human body where they show minimal genomic activity required for their survival. We hypothesized that it is not the latency itself but a timely, regionally restricted viral reactivation in a sub-set of host cells that plays a key role in disease development.

HHV-6 (HHV-6A and HHV-6B) and HHV-7 are unique HHVs that acquire latency by integration of the viral genome into sub-telomeric region of human chromosomes. HHV-6 reactivation has been linked to Alzheimer’s Disease, Chronic Fatigue Syndrome, and many other diseases. However, lack of viral activity in commonly tested biological materials including blood or serum strongly suggests tissue specific localization of active HHV-6 genome.

Here in this paper, we attempted to analyze active HHV-6 transcripts in postmortem tissue biopsies from a small cohort of ME/CFS patients and matched controls by fluorescence in situ hybridization using a probe against HHV-6 microRNA (miRNA), miR-aU14. Our results show abundant viral miRNA in various regions of the human brain and associated neuronal tissues including the spinal cord that is only detected in ME/CFS patients and not in controls.

Our findings provide evidence of tissue-specific active HHV-6 and EBV infection in ME/CFS, which along with recent work demonstrating a possible relationship between herpesvirus infection and ME/CFS, provide grounds for renewed discussion on the role of herpesviruses in ME/CFS.

Source: Prusty, Bhupesh K.; Kasimir, Francesca; Toomey, Danny; Liu, Zheng; Agnes Kaiping and Ariza, Maria Eugenia. Tissue specific signature of HHV-6 infection in ME/CFS. Front. Mol. Biosci. Sec. Molecular Diagnostics and Therapeutics. doi: 10.3389/fmolb.2022.1044964 https://www.frontiersin.org/articles/10.3389/fmolb.2022.1044964/abstract

Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals

Abstract:

Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer’s disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. ‘

Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.

Source: Griggs E, Trageser K, Naughton S, Yang EJ, Mathew B, Van Hyfte G, Hellmers L, Jette N, Estill M, Shen L, Fischer T, Pasinetti GM. Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals. bioRxiv [Preprint]. 2022 Nov 23:2022.11.23.517706. doi: 10.1101/2022.11.23.517706. PMID: 36451886; PMCID: PMC9709800. https://www.biorxiv.org/content/10.1101/2022.11.23.517706v1.full (Full text)

Persistent alveolar type 2 dysfunction and lung structural derangement in post-acute COVID-19

Abstract:

SARS-CoV-2 infection can manifest as a wide range of respiratory and systemic symptoms well after the acute phase of infection in over 50% of patients. Key questions remain on the long-term effects of infection on tissue pathology in recovered COVID-19 patients. To address these questions we performed multiplexed imaging of post-mortem lung tissue from 12 individuals who died post-acute COVID-19 (PC) and compare them to lung tissue from patients who died during the acute phase of COVID-19, or patients who died with idiopathic pulmonary fibrosis (IPF), and otherwise healthy lung tissue.

We find evidence of viral presence in the lung up to 359 days after the acute phase of disease, including in patients with negative nasopharyngeal swab tests. The lung of PC patients are characterized by the accumulation of senescent alveolar type 2 cells, fibrosis with hypervascularization of peribronchial areas and alveolar septa, as the most pronounced pathophysiological features. At the cellular level, lung disease of PC patients, while distinct, shares pathological features with the chronic pulmonary disease of IPF. which may help rationalize interventions for PC patients.

Altogether, this study provides an important foundation for the understanding of the long-term effects of SARS-CoV-2 pulmonary infection at the microanatomical, cellular, and molecular level.

Source: André F. Rendeiro, Hiranmayi Ravichandran, Junbum Kim, Alain C. Borczuk, Olivier Elemento, Robert E. Schwartz. Persistent alveolar type 2 dysfunction and lung structural derangement in post-acute COVID-19. medRxiv 2022.11.28.22282811; doi: https://doi.org/10.1101/2022.11.28.22282811 https://www.medrxiv.org/content/10.1101/2022.11.28.22282811v1.full-text  (Full text)

Identifying Profiles and Symptoms of Patients With Long COVID in France: Data Mining Infodemiology Study Based on Social Media

Abstract:

Background: Long COVID-a condition with persistent symptoms post COVID-19 infection-is the first illness arising from social media. In France, the French hashtag #ApresJ20 described symptoms persisting longer than 20 days after contracting COVID-19. Faced with a lack of recognition from medical and official entities, patients formed communities on social media and described their symptoms as long-lasting, fluctuating, and multisystemic. While many studies on long COVID relied on traditional research methods with lengthy processes, social media offers a foundation for large-scale studies with a fast-flowing outburst of data.

Objective: We aimed to identify and analyze Long Haulers’ main reported symptoms, symptom co-occurrences, topics of discussion, difficulties encountered, and patient profiles.

Methods: Data were extracted based on a list of pertinent keywords from public sites (eg, Twitter) and health-related forums (eg, Doctissimo). Reported symptoms were identified via the MedDRA dictionary, displayed per the volume of posts mentioning them, and aggregated at the user level. Associations were assessed by computing co-occurrences in users’ messages, as pairs of preferred terms. Discussion topics were analyzed using the Biterm Topic Modeling; difficulties and unmet needs were explored manually. To identify patient profiles in relation to their symptoms, each preferred term’s total was used to create user-level hierarchal clusters.

Results: Between January 1, 2020, and August 10, 2021, overall, 15,364 messages were identified as originating from 6494 patients of long COVID or their caregivers. Our analyses revealed 3 major symptom co-occurrences: asthenia-dyspnea (102/289, 35.3%), asthenia-anxiety (65/289, 22.5%), and asthenia-headaches (50/289, 17.3%). The main reported difficulties were symptom management (150/424, 35.4% of messages), psychological impact (64/424,15.1%), significant pain (51/424, 12.0%), deterioration in general well-being (52/424, 12.3%), and impact on daily and professional life (40/424, 9.4% and 34/424, 8.0% of messages, respectively). We identified 3 profiles of patients in relation to their symptoms: profile A (n=406 patients) reported exclusively an asthenia symptom; profile B (n=129) expressed anxiety (n=129, 100%), asthenia (n=28, 21.7%), dyspnea (n=15, 11.6%), and ageusia (n=3, 2.3%); and profile C (n=141) described dyspnea (n=141, 100%), and asthenia (n=45, 31.9%). Approximately 49.1% of users (79/161) continued expressing symptoms after more than 3 months post infection, and 20.5% (33/161) after 1 year.

Conclusions: Long COVID is a lingering condition that affects people worldwide, physically and psychologically. It impacts Long Haulers’ quality of life, everyday tasks, and professional activities. Social media played an undeniable role in raising and delivering Long Haulers’ voices and can potentially rapidly provide large volumes of valuable patient-reported information. Since long COVID was a self-titled condition by patients themselves via social media, it is imperative to continuously include their perspectives in related research. Our results can help design patient-centric instruments to be further used in clinical practice to better capture meaningful dimensions of long COVID.

Source: Déguilhem A, Malaab J, Talmatkadi M, Renner S, Foulquié P, Fagherazzi G, Loussikian P, Marty T, Mebarki A, Texier N, Schuck S. Identifying Profiles and Symptoms of Patients With Long COVID in France: Data Mining Infodemiology Study Based on Social Media. JMIR Infodemiology. 2022 Nov 22;2(2):e39849. doi: 10.2196/39849. PMID: 36447795; PMCID: PMC9685517.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685517/ (Full text)