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)

Post-COVID-19 cholangiopathy: Systematic review

Abstract:

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy.

Aim: To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy.

Methods: Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/).

Results: The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes.

Conclusion: Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.

Source: Rasheed MA, Ballotin VR, Bigarella LG, Soldera J. Post-COVID-19 cholangiopathy: Systematic review. World J Methodol. 2023 Sep 20;13(4):296-322. doi: 10.5662/wjm.v13.i4.296. PMID: 37771872; PMCID: PMC10523251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523251/ (Full text)

A brief overview of SARS-CoV-2 infection and its management strategies: a recent update

Abstract:

The COVID-19 pandemic has become a global health crisis, inflicting substantial morbidity and mortality worldwide. A diverse range of symptoms, including fever, cough, dyspnea, and fatigue, characterizes COVID-19. A cytokine surge can exacerbate the disease’s severity. This phenomenon involves an increased immune response, marked by the excessive release of inflammatory cytokines like IL-6, IL-8, TNF-α, and IFNγ, leading to tissue damage and organ dysfunction.

Efforts to reduce the cytokine surge and its associated complications have garnered significant attention. Standardized management protocols have incorporated treatment strategies, with corticosteroids, chloroquine, and intravenous immunoglobulin taking the forefront. The recent therapeutic intervention has also assisted in novel strategies like repurposing existing medications and the utilization of in vitro drug screening methods to choose effective molecules against viral infections.

Beyond acute management, the significance of comprehensive post-COVID-19 management strategies, like remedial measures including nutritional guidance, multidisciplinary care, and follow-up, has become increasingly evident. As the understanding of COVID-19 pathogenesis deepens, it is becoming increasingly evident that a tailored approach to therapy is imperative.

This review focuses on effective treatment measures aimed at mitigating COVID-19 severity and highlights the significance of comprehensive COVID-19 management strategies that show promise in the battle against COVID-19.

Source: Das A, Pathak S, Premkumar M, Sarpparajan CV, Balaji ER, Duttaroy AK, Banerjee A. A brief overview of SARS-CoV-2 infection and its management strategies: a recent update. Mol Cell Biochem. 2023 Sep 24. doi: 10.1007/s11010-023-04848-3. Epub ahead of print. PMID: 37742314. https://link.springer.com/article/10.1007/s11010-023-04848-3 (Full text)

Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes

Abstract:

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19.
We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT).
Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.
Source: Mrakic-Sposta S, Vezzoli A, Garetto G, Paganini M, Camporesi E, Giacon TA, Dellanoce C, Agrimi J, Bosco G. Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes. Metabolites. 2023; 13(10):1032. https://doi.org/10.3390/metabo13101032 https://www.mdpi.com/2218-1989/13/10/1032 (Full text)

Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents

Abstract:

SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenotypes with increasing prevalence. Its manifestation and risk factors remain elusive. In this monocentric study, we hypothesized that atopy, the tendency to produce an exaggerated immunoglobulin E (IgE) immune response, is a risk factor for the manifestation of pediatric PCC.
We present a patient cohort (n = 28) from an early pandemic period (2021–2022) with comprehensive evaluations of phenotypes, pulmonary function, and molecular investigations. PCC predominantly affected adolescents and presented with fatigue, dyspnea, and post-exertional malaise. Sensitizations to aeroallergens were found in 93% of cases.
We observed elevated IgE levels (mean 174.2 kU/L, reference < 100 kU/L) regardless of disease severity. Concurrent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) was found in 29% of patients that also faced challenges in school attendance. ME/CFS manifestation was significantly associated with elevated immunoglobulin G subclasses IgG3 (p < 0.05) and IgG4 (p < 0.05). A total of 57% of patients showed self-limiting disease courses with mean recovery at 12.7 months (range 5–25 months), 29% at 19.2 months (range 12–30 months), and the rest demonstrated overall improvement. These findings offer additional insights into immune dysregulation as a risk factor for pediatric PCC.
Source: Körner RW, Bansemir OY, Franke R, Sturm J, Dafsari HS. Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents. Children. 2023; 10(10):1598. https://doi.org/10.3390/children10101598 https://www.mdpi.com/2227-9067/10/10/1598 (Full text)

Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation

Abstract:

The long-term effects of COVID-19 on cognitive function have become an area of increasing concern. This paper provides an overview of characteristics, risk factors, possible mechanisms, and management strategies for cognitive dysfunction in post-COVID-19 condition (PCC).

Prolonged cognitive dysfunction is one of the most common impairments in PCC, affecting between 17% and 28% of the individuals more than 12 weeks after the infection and persisting in some cases for several years. Cognitive dysfunctions can be manifested as a wide range of symptoms including memory impairment, attention deficit, executive dysfunction, and reduced processing speed. Risk factors for developing PCC, with or without cognitive impairments, include advanced age, preexisting medical conditions, and the severity of acute illness. The underlying mechanisms remain unclear, but proposed contributors include neuroinflammation, hypoxia, vascular damage, and latent virus reactivation not excluding the possibility of direct viral invasion of the central nervous system, illustrating complex viral pathology.

As the individual variation of the cognitive impairments is large, a neuropsychological examination and a person-centered multidimensional approach are required. According to the World Health Organization, limited evidence on COVID-19-related cognitive impairments necessitates implementing rehabilitation interventions from established practices of similar conditions. Psychoeducation and compensatory skills training are recommended. Assistive products and environmental modifications adapted to individual needs might be helpful. In specific attention- and working memory dysfunctions, cognitive training—carefully monitored for intensity—might be effective for people who do not suffer from post-exertional malaise. Further research is crucial for evidence-based interventions specific to COVID-19-related cognitive impairments.

Source: Möller M, Borg K, Janson C, Lerm M, Normark J, Niward K. Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation. J Intern Med. 2023 Sep 27. doi: 10.1111/joim.13720. Epub ahead of print. PMID: 37766515. https://onlinelibrary.wiley.com/doi/10.1111/joim.13720 (Full text)

Re-visiting professional ethics in psychotherapy: Reflections on the use of talking therapies as a supportive adjunct for myalgic encephalomyelitis / chronic fatigue syndrome and ‘medically unexplained symptoms’

Abstract:

Following years of debate over the effectiveness of cognitive behavioural therapy for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS), public health bodies in the UK and beyond have determined that no psychotherapy is clinically proven for this patient group.

In the field of ME/CFS and the wider arena of ‘medically unexplained symptoms’ (MUS), patient survey data and qualitative research capturing patient experiences and psychotherapist attitudes suggest that therapeutic practice may sometimes fall short of required ethical standards. This raises questions about how psychotherapists can safely support, as opposed to treat, people with these debilitating conditions.

We consider four ethical principles that feature throughout psychotherapists’ codes of practice, those of respect, competence, responsibility, and integrity, and discuss examples of good and poor practice in this arena as evinced by recent empirical literature.

Following this, we offer a variety of suggestions to help strengthen ethical psychotherapy practice among patients with ME/CFS and other MUS. In terms of practitioner education, we recommend greater emphasis on humility and reflexive practice, exploration of personal as well professional ethics, and integration of patient expertise-by-experience, accompanied with latest evidence, into foundational and on-going training.

In terms of practice, we suggest consideration of formalized patient-focused feedback systems and greater transparency visà-vis patient access to clinical notes. Finally, we underline the importance of elevating patients from mere subjects to co-producers of psychotherapy research.

Source: Joanne Hunt, Charlotte Blease. Re-visiting professional ethics in psychotherapy: Reflections on the use of talking therapies as a supportive adjunct for myalgic encephalomyelitis / chronic fatigue syndrome and ‘medically unexplained symptoms.’ OSF preprints. https://osf.io/2m9eb/ (Full text)

Assessing Functional Capacity in ME/CFS: A Patient Informed Questionnaire

Abstract:

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Effective tools to assess functional capacity (FC) are severely lacking which has significant consequences for timely diagnosis, assessments for patient disability benefits and assessing the impact and effectiveness of interventions.

In interventional research the inability to assess FC can result in an incomplete assessment of the potential effect of the intervention. Specifically of concern is that if an intervention is effective in reducing symptom load, patients may increase their activity level to reach a pre-intervention symptom load. Thus, if FC is not accurately assessed, beneficial treatment outcomes may be missed.

To address this issue, using extensive, repeated patient feedback we have developed a new questionnaire, FUNCAP, to achieve optimal FC assessment in ME/CFS patients.

The questionnaire covers eight domains and activity types: A. Personal hygiene / basic functions, B. Walking / movement, C. Being upright, D. Activities in the home, E. Communication, F. Activities outside the home, G. Reactions to light and sound, and H. Concentration.

Through five rounds of anonymous web-based surveys and a further test – retest validation round, two versions of the questionnaire were developed; a longer version comprising 55 questions (FUNCAP55) to improve diagnostic and disability benefit/ insurance FC assessments and a shorter version (FUNCAP27) for interventional research and less extensive FC assessments. FUNCAP may also be useful in other conditions where fatigue and PEM is present, such as Long Covid.

Source: Sommerfelt, K.; Schei, T.; Seton, K.A.; Carding, S.R. Assessing Functional Capacity in ME/CFS: A Patient Informed Questionnaire. Preprints 2023, 2023092091 https://www.preprints.org/manuscript/202309.2091/v1 (Full text available as PDF file) Final version https://www.mdpi.com/2077-0383/13/12/3486 (Full text)

Is there a role for traditional and complementary medicines in managing chronic fatigue? A systematic review of randomized controlled trials

Abstract:

Introduction: Chronic fatigue syndrome (CFS) is an increasingly common condition that is challenging to treat due to unclear etiology and a lack of consensus on clinical diagnosis and treatment guidance. Many affected people resorted to using traditional and complementary medicines (T&CMs). However, the evidence for T&CMs for CF has been inconclusive and continues to evolve. The study aims to identify, summarize and assess the most recent evidence on the efficacy and safety of T&CMs for CFS.

Methods: Randomized controlled trials (RCTs) investigating T&CMs for CFS published in English of Chinese between 1 January 2013 and 31 December 2022 were searched from 7 databases. RCTs comparing T&CMs with no treatment, placebo, or pharmacological medicine were included, irrespective of language or blinding.

The Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM) and the Cochrane Collaboration’s Risk of Bias tool were used to evaluate the quality and risk of bias of included studies.

Results: A total of 62 RCTs investigating 43 types of T&CMs and involving 5,231 participants with CFS were included in this review. The primary outcome measures mainly included the scoring of fatigue symptoms using the validated tool Fatigue Scale-14 (FS-14) or the TCM syndrome score.

The main interventions showing overall efficacy were Chaihu Guizhi Decoction and Buzhong Yiqi combined with Xiao Chaihu Decoction, and 148 ingredients were identified, including Astragali Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Bupleuri Radix.

The most significant effect was the improvement of fatigue, followed by TCM-diagnosed symptoms and other psychological conditions. No serious adverse effect had been reported. However, the quality of the RCTs included RCTs were found to be suboptimal, and the risk of bias remained uncertain.

Conclusions: Some evidence from RCTs supported the efficacy and safety of T&CM in CFS. However, given the methodological and quality heterogenicity of the included studies, the recommendations of T&CMs in treating CFS remain inconclusive. To develop better quality evidence about T&CMs for CFS, future studies should employ more objective diagnosis standards and outcome measurements, larger sample size, and better bias control, and ensure the compliance with the corresponding reporting guidelines.

Source: Yuxiao Li, Jingya Yang, Chi Ian Chau, Junnan Shi, Xianwen Chen, Hao Hu, Carolina Oi Lam Ung. Is there a role for traditional and complementary medicines in managing chronic fatigue? A systematic review of randomized controlled trials. Frontiers in Pharmacology, Volume 14, 2023. https://www.frontiersin.org/articles/10.3389/fphar.2023.1266803/abstract

Investigating the Effect of COVID-19 Infection on Professional Athletes’ Post-infection With a Focus on Fatigue and Chronic Fatigue Syndrome

Abstract:

Introduction and objectives: COVID-19 has been reported to cause long-term sequela including persistent fatigue and Chronic Fatigue Syndrome (CFS) in the general population. However, it remains to be seen if similar effects are observed in an athlete population. The aetiology and pathophysiology are poorly understood but is thought to be multi-factorial. Patient reported outcome measures are commonly used to improve patient-centred outcomes (PROMs). They are essential to assess patient quality of life post-COVID infection. This paper aims to assess the effect of COVID-19 on athletes’ long-term fatigue and CFS and identify the PROMs used to characterise this.

Methodology: Articles were selected for extraction based on the eligibility criteria and PRISMA guidelines. The inclusion criteria required papers to assess competitive athletes over eighteen years of age who were clinically diagnosed with COVID-19. Articles were extracted to assess different variables including type of sport, type of athlete and ethnicity. Key terms were obtained using MeSH trees and utilised with Web of Science and NCBI Pubmed. Papers were graded by quality using the Hawker quality assessment tool.

Results and discussion: Forty articles (N=40) were identified for full-text screening (N=8). Eight were selected for extraction based on the eligibility criteria. Data was obtained on athlete characteristics, sport characteristics, properties of PROM measurement techniques and fatigue presentation. Male athletes were found to be 10-50% more likely than female athletes to suffer from persistent fatigue symptoms (N=2). Persistent fatigue was present in 9-10% Athletes from mixed backgrounds and genders (N=2). Initial fatigue was documented to be between 47-56% (N=2). A heterogenous range of PROMs were utilised to assess symptoms including fatigue and excluded emotional or mental fatigue.

Conclusion: COVID-19 is associated with signs of persisting fatigue and potentially CFS in athlete populations. More work needs to be done to develop standardised and validated PROMs specific to CFS.

Source: Sarwary, Reza and Tareen, Manahil and Hocaoglu, Mevhibe, Investigating the Effect of COVID-19 Infection on Professional Athletes’ Post-infection With a Focus on Fatigue and Chronic Fatigue Syndrome (January 16, 2023). Available at SSRN: https://ssrn.com/abstract=4573649 or http://dx.doi.org/10.2139/ssrn.4573649 (Full text available as PDF file)