The influence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) family history on patients with ME/CFS

Abstract:

Aim: It is unclear if individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with family histories of ME/CFS differ from those with ME/CFS without this family history. To explore this issue, quantitative data from patients with ME/CFS and controls were collected, and we examined those with and without family histories of ME/CFS.

Methods: The samples included 400 patients with ME/CFS, and a non-ME/CFS chronic illness control group of 241 patients with multiple sclerosis (MS) and 173 with post-polio syndrome (PPS).

Results: Confirming findings from prior studies, those with ME/CFS were more likely to have family members with ME/CFS than controls. We found family histories of ME/CFS were significantly higher (18%) among the ME/CFS group than the non-ME/CFS controls (3.9%). In addition, patients with ME/CFS who had family histories of ME/CFS were more likely to have gastrointestinal symptoms than those with ME/CFS without those family histories.

Conclusions: Given the recent reports of gastrointestinal difficulties among those with ME/CFS, our findings might represent one predisposing factor for the emergence of ME/CFS.
Source: Jason LA, Ngonmedje S. The influence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) family history on patients with ME/CFS. Explor Med. 2024;5:185–92. https://doi.org/10.37349/emed.2024.00215 https://www.explorationpub.com/Journals/em/Article/1001215 (Full text)

The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives

Abstract:

Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established.

Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS.

In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS.

Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.

Source: Andreas Stallmach, Stefanie Quickert, Christian Puta, Philipp A. Reuken. The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives. Front. Immunol., 27 March 2024, Sec. Microbial Immunology, Volume 15 – 2024. https://doi.org/10.3389/fimmu.2024.1352744 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1352744/full (Full text)

Clinical features of Japanese patients with gastrointestinal long-COVID symptoms

Introduction:

Although the development of new therapeutic approaches and vaccines has decreased coronavirus disease 2019 (COVID-19)-associated mortality, prolonged systemic symptoms after COVID-19, termed long-COVID, have been a major concern, considering their potential impact on health-related quality of life (QOL). Gastrointestinal (GI) symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID even months after the initial COVID-19 symptoms have resolved.

Although emerging evidence suggests that GI symptoms in long-COVID are affected by the dysregulation of the immune system or ongoing inflammation and damage to the GI tract caused by the initial COVID-19 infection, the clinical features of patients with GI long-COVID symptoms remain elusive. Our study aimed to clarify these features.

Source: Kazuma Yagi, Takanori Asakura, Hideki Terai, Keiko Ohgino, Katsunori Masaki, Ho Namkoong, Shotaro Chubachi, Jun Miyata, Ichiro Kawada, Nobuhiro Kodama, Satoshi Sakamoto, Akira Umeda, Takashi Ishiguro, Makoto Ishii, Koichi Fukunaga. JGH Open. First published: 06 December 2023 https://doi.org/10.1002/jgh3.13006 https://onlinelibrary.wiley.com/doi/full/10.1002/jgh3.13006 (Full text)

Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review

Abstract:

The emergence of post-COVID-19 syndrome (PCS), a complex and multifactorial condition that follows the acute COVID-19 infection, has raised serious concerns within the global medical community. Concurrently, Irritable Bowel Syndrome (IBS), a widespread chronic gastrointestinal (GI) dysfunction, is considered to be one of the most common disorders of gut–brain interaction (DGBI) that significantly affects the quality of life and social functioning of patients. PCS presents a wide range of symptoms and GI manifestations, including IBS.
This review aims to analyze the GI involvement and the prolonged symptoms of COVID-19 infection as part of PCS, in order to explore the potential development of post-infection IBS (PI-IBS) in COVID-19 patients. Irritating factors such as enteric infection, psychosocial conditions, food antigens, and antibiotics may lead to abnormalities in the physiological function of the GI system and could be involved in the development of PI-IBS. Through the presentation of the pathophysiological mechanisms and epidemiological studies that assessed the prevalence of IBS as part of PCS, we attempted to provide a better understanding of the long-term consequences of COVID-19 and the pathogenesis of PI-IBS.
Even though PI-IBS is becoming a global challenge, there are only a few studies about it and therefore limited knowledge. Currently, the majority of the existing treatment options are referred to non-COVID-19-associated DGBIs. Forthcoming studies may shed light on the mechanisms of PI-IBS that could be targeted for treatment development. Paramythiotis D, Karlafti E, Didagelos M, Fafouti M, Veroplidou K, Protopapas AA, Kaiafa G, Netta S, Michalopoulos A, Savopoulos C. Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review. Medicina. 2023; 59(11):1961. https://doi.org/10.3390/medicina59111961 https://www.mdpi.com/1648-9144/59/11/1961 (Full text)
Source:

Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study

Abstract:

Objective: To determine if patients that develop lingering neurologic symptoms of fatigue and “brain fog” after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology.

Design: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function.

Results: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion.

Conclusions: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19.

Source: Wright TJ, Pyles RB, Sheffield-Moore M, Deer RR, Randolph KM, McGovern KA, Danesi CP, Gilkison CR, Ward WW, Vargas JA, Armstrong PA, Lindsay SE, Zaidan MF, Seashore J, Wexler TL, Masel BE, Urban RJ. Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study. Mol Cell Endocrinol. 2023 Oct 8:112071. doi: 10.1016/j.mce.2023.112071. Epub ahead of print. PMID: 37816478. https://www.sciencedirect.com/science/article/abs/pii/S0303720723002228

Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts

Abstract:

Background: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID).

Aim: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations.

Methods: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae.

Results: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans.

Conclusion: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

Source: Sherif ZA, Deverapalli M, Challa SR, Martirosyan Z, Whitesell P, Pizuorno AM, Naqvi Z, Tulloch IK, Oskrochi G, Brim H, Ashktorab H. Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts. World J Methodol. 2023 Sep 20;13(4):323-336. doi: 10.5662/wjm.v13.i4.323. PMID: 37771866; PMCID: PMC10523249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523249/ (Full text)

Risks of digestive diseases in long COVID: Evidence from a large-scale cohort study

Abstract:

Objectives This study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on the long-term risk of digestive diseases in the general population.

Design Large-scale population-based cohort study based on a prospective cohort.

Setting UK Biobank cohort linked to multiple nationwide electronic health records databases.

Participants The cohort consisted of 112,311 individuals who survived the initial 30 days following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as two control groups: a contemporary group (n = 359,671) without any history of COVID-19, and a historical control group (n = 370,979) that predated the COVID-19 outbreak.

Main outcome measures Main outcomes were predefined digestive diseases. Hazard ratios and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting.

Results Compared with the contemporary control group, patients with previous COVID-19 infection had higher risks of digestive diseases, including functional gastrointestinal disorders (hazard ratios [HR] 1.95 (95% CI 1.62 to 2.35)); peptic ulcer disease (HR 1.27 (1.04 to 1.56)); gastroesophageal reflux disease (GERD) (HR 1.46 (1.34 to 1.58)); inflammatory bowel diseases (HR 1.40 (1.02 to 1.90)); gallbladder disease (HR 1.28 (1.13 to 1.46)); severe liver disease (HR 1.46 (1.12 to 1.90)); non-alcoholic liver disease (HR 1.33 (1.15 to 1.55)); and pancreatic disease (HR 1.43 (1.17 to 1.74)). The risks of GERD were stepwise increased with severity of the acute phase of COVID-19 infection. The results were consistent when using the historical cohort as the control group.

Conclusions Our study provides important insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing gastrointestinal disorders, with stepwise increased risk with the severity and persisting even after one year follow-up.

Source: Yuying Ma, Lijun Zhang, Rui Wei, Weiyu Dai, Ruijie Zeng, Dongling Luo, Rui Jiang, Huihuan Wu, Zewei Zhuo, Qi Yang, Jingwei Li, Felix W Leung, Chongyang Duan, Weihong Sha, Hao Chen. Risks of digestive diseases in long COVID: Evidence from a large-scale cohort study. medRxiv 2023.04.25.23289080; doi: https://doi.org/10.1101/2023.04.25.23289080 https://www.medrxiv.org/content/10.1101/2023.04.25.23289080v1.full-text (Full text)

Symptom presentation and quality of life are comparable in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and post COVID-19 condition

Abstract:
Background and Οbjective: Considerable overlap exists in the clinical presentation of Post COVID-19 Condition and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The current study aimed to compare symptoms and patient-reported Quality of Life (QoL) among people with Post COVID-19 Condition and ME/CFS in Australia. Methods: QoL data was collected from n=61 ME/CFS patients, n=31 Post COVID-19 Condition patients, and n=54 Healthy Controls (HCs) via validated instruments. The ME/CFS and Post COVID-19 Condition participants also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for Post COVID-19 Condition. Study variables were compared with Chi-square, Fisher’s exact, Fisher-Freeman-Halton, Mann-Whitney U, and Kruskal-Wallis H tests using Statistical Package for the Social Sciences version 29. Symptom clusters among the two illness cohorts were identified with hierarchical cluster analysis.
Results: ME/CFS was associated with a higher prevalence of short-term memory loss (p=0.039), muscle weakness (p<0.001), lymphadenopathy (p=0.013), and nausea (p=0.003). People with ME/CFS also reported more severe light-headedness (p=0.011) and more frequent unrefreshed sleep (p=0.011), but less frequent heart palpitations (p=0.040). Symptom prevalence, severity, and frequency were otherwise comparable. Few differences existed in the QoL of the two illness cohorts, both of which returned significantly impaired QoL scores when compared with HCs (p<0.001). Cluster analysis of symptom prevalence revealed four clusters: 1) Low gastrointestinal, low neurosensory; 2) Moderate gastrointestinal, low orthostatic and memory loss; 3) Moderate gastrointestinal, high orthostatic and memory loss; and 4) High gastrointestinal, high pain, which did not differ in sociodemographic information, illness status, or diagnostic criteria met.
Conclusions: Post COVID-19 Condition and ME/CFS are remarkably similar in presentation and, like ME/CFS, Post COVID-19 Condition has a profound and negative impact on patient QoL. Gastrointestinal symptoms may have a role in determining ME/CFS and Post COVID-19 Condition subtypes.
Source: Weigel B, Eaton-Fitch N, Thapaliya K, Marshall-Gradisnik S. Symptom presentation and quality of life are comparable in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and post COVID-19 condition. Population Medicine. 2023;5(Supplement):A372. doi:10.18332/popmed/165669.  http://www.populationmedicine.eu/Symptom-presentation-and-quality-of-life-are-comparable-in-Myalgic-Encephalomyelitis,165669,0,2.html

Long-term gastrointestinal outcomes of COVID-19

Abstract:

A comprehensive evaluation of the risks and 1-year burdens of gastrointestinal disorders in the post-acute phase of COVID-19 is needed but is not yet available. Here we use the US Department of Veterans Affairs national health care databases to build a cohort of 154,068 people with COVID-19, 5,638,795 contemporary controls, and 5,859,621 historical controls to estimate the risks and 1-year burdens of a set of pre-specified incident gastrointestinal outcomes.

We show that beyond the first 30 days of infection, people with COVID-19 exhibited increased risks and 1-year burdens of incident gastrointestinal disorders spanning several disease categories including motility disorders, acid related disorders (dyspepsia, gastroesophageal reflux disease, peptic ulcer disease), functional intestinal disorders, acute pancreatitis, hepatic and biliary disease.

The risks were evident in people who were not hospitalized during the acute phase of COVID-19 and increased in a graded fashion across the severity spectrum of the acute phase of COVID-19 (non-hospitalized, hospitalized, and admitted to intensive care). The risks were consistent in comparisons including the COVID-19 vs the contemporary control group and COVID-19 vs the historical control group as the referent category.

Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19. Post-covid care should involve attention to gastrointestinal health and disease.

Source: Xu, E., Xie, Y. & Al-Aly, Z. Long-term gastrointestinal outcomes of COVID-19. Nat Commun 14, 983 (2023). https://doi.org/10.1038/s41467-023-36223-7 https://www.nature.com/articles/s41467-023-36223-7 (Full text)

Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection

Abstract:

Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.

Source: Rizvi A, Ziv Y, Crawford JM, Trindade AJ. Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection. Gastroenterol Clin North Am. 2023 Mar;52(1):139-156. doi: 10.1016/j.gtc.2022.09.002. PMID: 36813422; PMCID: PMC9940919. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940919/ (Full text)