Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis

Abstract:

Background: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic.

Objectives: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID.

Design: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed.

Data sources and methods: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages ‘meta’ and ‘metafor’.

Results: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06-0.22, I 2 = 99%] and 0.22 (95% CI, 0.10-0.41, I 2 = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04-0.38, I 2 = 96%), 0.06 (95% CI, 0.03-0.11, I 2 = 98%), 0.20 (95% CI, 0.08-0.43, I 2 = 98%), and 0.17 (95% CI, 0.10-0.27, I 2 = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04-0.23, I 2 = 98%), 0.20 (95% CI, 0.06-0.50, I 2 = 97%), and 0.17 (95% CI, 0.06-0.37, I 2 = 96%), respectively.

Conclusion: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.

Source: Choudhury A, Tariq R, Jena A, Vesely EK, Singh S, Khanna S, Sharma V. Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis. Therap Adv Gastroenterol. 2022 Aug 19;15:17562848221118403. doi: 10.1177/17562848221118403. PMID: 36004306; PMCID: PMC9393939. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393939/ (Full text)

Experiences of pain in paediatric chronic fatigue syndrome/myalgic encephalomyelitis: a single-centre qualitative study

Abstract:

Background: Moderate to severe pain affects up to two-thirds of children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and is associated with worse fatigue and physical functioning. This research aims to gain a greater insight into pain experienced by these children.

Methods: Thematic analysis of qualitative data from semistructured interviews with 13 children with CFS/ME (mean age=15.3 years, 67% female) was completed.

Results: Thematic analysis enabled construction of three themes: children’s wide-ranging experiences of pain, negative impact of pain and lack of effective treatment for pain and nine subthemes. The first theme demonstrated highly varied pain experiences, ranging from ‘like [being]… on fire’, like ‘being stabbed’ to ‘like…lead’. Children experienced pain in multiple sites and with wide-ranging frequency and severity. The second theme highlighted the profound negative impact of pain on multiple aspects of children’s lives. Physical activity was severely impaired; some children ‘couldn’t leave bed’ or ‘couldn’t…brush [their] own hair’. Abdominal pain meant some would ‘go…days without eating’. Pain substantially impacted on mental health, leaving children feeling ‘agitated’, experiencing ‘really bad panic attacks’ or making them ‘[want to] breakdown’. Children felt they ‘can’t do the things that everyone else can do’, had ‘missed out’ and are ‘behind everyone’. Some avoided socialising as they ‘don’t want to stop everyone else’. The final theme demonstrates the absence of adequate treatment for pain, with participants reporting ‘nothing has ever really got rid of it’ and only ‘slightly [takes] the edge off’ and other experiencing side effects.

Conclusions: Pain in paediatric CFS/ME is highly variable, common and often results in severe physical limitation and poor mental health. Effective treatments for pain represent an unmet need.

Source: Serafimova T, Ascough C, Parslow RM, Crawley E. Experiences of pain in paediatric chronic fatigue syndrome/myalgic encephalomyelitis: a single-centre qualitative study. BMJ Paediatr Open. 2022 Feb;6(1):e001201. doi: 10.1136/bmjpo-2021-001201. Epub 2022 Feb 15. PMID: 36053633. https://bmjpaedsopen.bmj.com/content/6/1/e001201 (Full text)

NeuroCOVID-19: a critical review

Abstract:

Background: The COVID-19 pandemic has challenged neurologists since its early days. Neurology consultation services were then overloaded by emergency department and intensive-care patients with acute neurological syndromes. These complications are better explained today, but the growing number of patients with reported longstanding neurological symptoms constitute an emerging, complex, and still poorly understood phenomenon.

Objective: This review summarizes data on relevant neurological manifestations of acute SARS-CoV-2 infection and lasting post-infectious disease, also known as Long COVID. The complex history of Long COVID is examined to illustrate the upsides and challenges imposed by the active participation of patient communities in the production of medical knowledge.

Methods: Narrative review.

Results: Infection with the severe acute respiratory syndrome coronavirus 2 is associated with encephalopathy/delirium, cerebrovascular disease, headache, and peripheral nervous system involvement. Long COVID is a living concept jointly defined by patient communities, physicians and scientists, including neurologists.

Conclusion: Co-production of Long COVID knowledge between scientists and patients has initiated an era of patient-led research and evidence-based activism that acts as a two-edged sword – putting patient’s suffering in the spotlight, but with a tradeoff in methodological consistency.

Source: Guedes BF. NeuroCOVID-19: a critical review. Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):281-289. doi: 10.1590/0004-282X-ANP-2022-S136. PMID: 35976326. https://www.scielo.br/j/anp/a/v6c3Xcvq4PkkD3HvKtT7DJN/?lang=en  (Full tex)

Post COVID syndrome: A novel challenge and threat to international health

Abstract:

The global pandemic caused by the SARS-CoV-2 virus has affected every continent worldwide. The novelty of this virus, its mutations and the rapid speed and unprecedented rate at which it has torn through the global community has in turn lead to an innate lack of knowledge and information about the actual disease caused and the severity of the complications associated with COVID-19.

The SARS-CoV-2 virus has been infecting individuals since 2019 and now as of 2022 has been circulating for just over 2 years within the global populous. As the number of cases have risen globally over this period (some of which having contracted the virus twice) further endeavours have been undertaken to better understand the pathogenesis and natural progression of the disease. A condition reported in some cases with extended bouts of sickness or symptoms following the initial infection with COVID was labelled “long COVID” towards the earlier phases of the pandemic (in the spring of 2020), but has only recently gained the global media and medical attention due to its affliction of more individuals on a global basis and has thus warranted further investigation.

Long COVID is described as a persistent, long-term state of poor health following an infection with COVID-19. The effect of Long COVID is multisystemic in nature with a wide array of signs and symptoms. The most commonly reported clinical features of long COVID are: headaches, myalgia, chest pain, rashes, abdominal pain, shortness of breath, palpitations, anosmia, persistent cough, brain fogs, forgetfulness, depression, insomnia, fatigue and anxiety. This research aims to explore the symptomatology, pathophysiology as well as the treatment and prevention of Long COVID.

Source: Banerjee I, Robinson J, Leclézio A, Sathian B, Banerjee I. Post COVID syndrome: A novel challenge and threat to international health. Nepal J Epidemiol. 2022 Jun 30;12(2):1215-1219. doi: 10.3126/nje.v12i2.46149. PMID: 35974973; PMCID: PMC9374107.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374107/ (Full text)

Autoimmune Gene Expression Proling of Fingerstick Whole Blood in Chronic Fatigue Syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions.

The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS.

In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.

Methods: In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home.

RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.

Results: Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease.

From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to 2 patients with mild to moderate disease conditions.

These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases.

These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA).

Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).

Conclusions: Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity.

These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

Source: Zheng Wang, Michelle F. Waldman, Tara J. Basavanhally, Aviva R. Jacobs, et al. Autoimmune Gene Expression Proling of Fingerstick Whole Blood in Chronic Fatigue Syndrome. https://doi.org/10.21203/rs.3.rs-1942047/v1  (Full text)

The Advantages of an Integrative Approach in the Primary Healthcare of Post-COVID-19 and ME/CFS Patients

Abstract:

The coronavirus disease caused by the SARS-CoV-2 virus (COVID-19) pandemic has changed not only global epidemiological and economic developments but also the lives of every individual, with particular severity for patients.

The number of acute illness cases grew rapidly, significantly increasing the workload of hospitals, and simultaneously, new chronic diseases emerged, such as persistent post-COVID-19 syndrome (PPCS), with unclear etiology, symptoms, and complexity—similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Accordingly, the burden of chronic diseases poses new long-term challenges for primary healthcare and requires new approaches to patient care.

This chapter provides insight into the integrative approach to healthcare and focuses on potentially new solutions by implementing an integrative attitude to the treatment of post-COVID-19 and ME/CFS patients in primary healthcare.

Integrative health coaching contributes the holistic approach to patients’ overall health and resilience through cognitive practice and patient active engagement. The findings of this chapter can enrich the person-centered approach and healthcare system strengthening through holistic measures and systems thinking.

Source: Diana Araja, Angelika Krumina, Uldis Berkis, Zaiga Nora-Krukle and Modra Murovska. The Advantages of an Integrative Approach in the Primary Healthcare of Post-COVID-19 and ME/CFS Patients. DOI: 10.5772/intechopen.106013  https://www.intechopen.com/online-first/82708 (Full text)

Myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: A mixed-methods systematic review

Abstract:

Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a fluctuating complex condition. More common in women than men, it tends to develop between mid-20s and mid-40s, including the main childbearing age (15–45 years). There are currently no systematic reviews summarising evidence relating to ME/CFS and pregnancy. The lack of quality assessed, and systematic summary evidence makes it harder for people with ME/CFS to make informed decisions about pregnancy, and harder for health care professionals to offer evidence-based care. This mixed methods systematic review aims to examine and summarise existing evidence relating to ME/CFS and pregnancy, both in relation to pregnancy outcomes and experiences of pregnancy but also the effect of pregnancy on ME/CFS severity and symptoms.

Methods This review followed a convergent segregated design. Seven electronic databases, relevant grey literature, reference lists of relevant reviews, and reference lists and citations of all included studies, were searched. Where necessary, authors were contacted for additional information. Studies of any design published in English, reporting on ME/CFS and pregnancy/postpartum (up to two years), risk of pregnancy outcomes with ME/CFS, or experiences during pregnancy for mother, partner or health and social care professionals following pregnancy with ME/CFS were included. Three researchers performed screening, data extraction and quality assessments independently. Qualitative and quantitative literature was analysed separately using thematic and descriptive syntheses, respectively (meta-analysis was not appropriate). Findings were integrated through configuration.

Results Searches identified n=2,789 studies, n=10 met our inclusion criteria. There were five quantitative studies, two qualitative studies and three pieces of grey literature. Preliminary results suggest that evidence is conflicting. In the qualitative literature, one study suggested one participant thought pregnancy improved ME/CFS symptoms while the other noted a participant commented that ME/CFS may have adversely affected her pregnancy. Of the four quantitative studies that reported on ME severity during pregnancy, two suggested pregnancy negatively impacted on ME/CFS, one study found most women had no change in ME/CFS symptoms during pregnancy, and one found ME/CFS improved during pregnancy. Only one study reported on pregnancy outcomes, finding a higher rate of spontaneous abortions, and increased developmental and learning delays in infants born to mothers with ME/CFS.

Conclusion Current evidence on ME/CFS in pregnancy is limited, and findings are inconsistent. Studies are limited by small sample size and currently, there is no UK evidence. More high-quality research into ME/CFS and pregnancy is urgently needed to support the development of evidence-based guidelines on ME/CFS and pregnancy.

Source: Pearce M, Slack E, Pears K, et alOP72 Myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic reviewJ Epidemiol Community Health 2022;76:A35. https://jech.bmj.com/content/76/Suppl_1/A35.1

Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature

Abstract:

Introduction: Persistent debilitating fatigue is a frequent complaint in patients with systemic autoimmune rheumatic diseases (SARDs). Fatigue is, however, frequently overlooked in the clinic, and patients who successfully achieve remission of their disease, often still have a lowered quality of life due to its persistence. How similar is this fatigue to Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), what is this fatigue associated with, and what tools/approaches (if any), have resulted in the improvement of fatigue in these patients is poorly defined.

Areas covered: Similarities between the pathophysiology of ME/CFS, systemic sclerosis (SSc) and primary systemic vasculitides (PSV) are discussed, followed by an in-depth review of the prevalence and correlates of fatigue in these diseases. The authors reviewed literature from MEDLINE, APA PsycInfo, Embase, and CINAHL.

Expert opinion: Persistent fatigue is a prominent feature in SARDs and may not be associated with components commonly associated with disease activity and/or progression. Immune and metabolic commonalities exist between ME/CFS, SSc, and PSVs – suggesting that common pathways inherent to the diseases and fatigue may be present. We suggest that patients with features of ME/CFS need to be identified by treating physicians, as they may require alternative approaches to therapy to improve their quality of life.

Source: van Eeden C, Osman MS, Cohen Tervaert JW. Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature. Expert Rev Clin Immunol. 2022 Aug 31:1-22. doi: 10.1080/1744666X.2022.2116002. Epub ahead of print. PMID: 36045606. https://pubmed.ncbi.nlm.nih.gov/36045606/

Long Covid stigma: estimating burden and validating scale in a UK-based sample

Abstract:

Background: Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, behavioural or other attributes deemed to be undesirable. Long Covid is a predominantly multisystem condition that occurs in people with a history of SARSCoV2 infection, often resulting in functional disability.

Aim: To develop and validate a Long Covid Stigma Scale (LCSS); and to quantify the burden of Long Covid stigma.

Design and Setting: Follow-up of a co-produced community-based Long Covid online survey using convenience non-probability sampling.

Method: Thirteen questions on stigma were designed to develop the LCSS capturing three domains – enacted (overt experiences of discrimination), internalised (internalising negative associations with Long Covid and accepting them as self-applicable) and anticipated (expectation of bias/poor treatment by others) stigma. Confirmatory factor analysis tested whether LCSS consisted of the three hypothesised domains. Model fit was assessed and prevalence was calculated.

Results: 966 UK-based participants responded (888 for stigma questions), with mean age 48 years (SD: 10.7) and 85% female. Factor loadings for enacted stigma were 0.70-0.86, internalised 0.75-0.84, anticipated 0.58-0.87, and model fit was good. The prevalence of experiencing stigma at least ‘sometimes’ and ‘often/always’ was 95% and 76% respectively. Anticipated and internalised stigma were more frequently experienced than enacted stigma. Those who reported having a clinical diagnosis of Long Covid had higher stigma prevalence than those without.

Conclusion: This study establishes a scale to measure Long Covid stigma and highlights common experiences of stigma in people living with Long Covid.

Source: Marija Pantelic, Nida Ziauddeen, Mark Boyes, Margaret E O’Hara, Claire Hastie, Nisreen A Alwan. Long Covid stigma: estimating burden and validating scale in a UK-based sample. medRxiv 2022.05.26.22275585; doi: https://doi.org/10.1101/2022.05.26.22275585 (Full text)

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity

Abstract:

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively.

Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy.

Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.

Source: Kedor C, Freitag H, Meyer-Arndt L, Wittke K, Hanitsch LG, Zoller T, Steinbeis F, Haffke M, Rudolf G, Heidecker B, Bobbert T, Spranger J, Volk HD, Skurk C, Konietschke F, Paul F, Behrends U, Bellmann-Strobl J, Scheibenbogen C. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat Commun. 2022 Aug 30;13(1):5104. doi: 10.1038/s41467-022-32507-6. PMID: 36042189. https://www.nature.com/articles/s41467-022-32507-6 (Full text)