Tag: long covid review

Autonomic Manifestations of Long-COVID Syndrome

Abstract:

Purpose of review: Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.

Recent findings: Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.

Source: Hira R, Karalasingham K, Baker JR, Raj SR. Autonomic Manifestations of Long-COVID Syndrome. Curr Neurol Neurosci Rep. 2023 Nov 10. doi: 10.1007/s11910-023-01320-z. Epub ahead of print. PMID: 37947962. https://pubmed.ncbi.nlm.nih.gov/37947962/

Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems

Abstract:

Unprecedented worldwide health catastrophe due to the COVID-19 pandemic has ended up resulting in high morbidity and mortality rates. Even though many people recover from acute infection, there is rising concern regarding post-COVID-19 conditions (PCCs), often referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or “long COVID.”

The respiratory, cardiovascular, neurological, and endocrine systems are just a few of the many organ systems that can be impacted by this multifarious, complicated illness. The clinical manifestations of long COVID can vary among individuals and may include fatigue, dyspnea, chest pain, cognitive impairment, and new-onset diabetes, among others.

Although the underlying processes of long COVID are not fully understood, they probably involve unregulated immune response, persistent generation of pro-inflammatory cytokines (chronic inflammation), autoimmune-like reactions, persistent viral replication, and micro-clot formation.

To create successful treatments and care plans, it is essential to comprehend the immunological mechanisms causing these difficulties. The pathogenesis of long COVID should be clarified and potential biomarkers to help with diagnosis and treatment should be sought after. To reduce the burden of long COVID on people and healthcare systems around the world, the need for long-term monitoring and management of long COVID problems should be emphasized. It also underscores the significance of a multidisciplinary approach to patient care. The goal of this review is to carefully evaluate the clinical signs and symptoms of long COVID, their underlying causes, and any potential immunological implications.

Source: Bhattacharjee N, Sarkar P, Sarkar T. Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems. Physiol Int. 2023 Nov 9. doi: 10.1556/2060.2023.00256. Epub ahead of print. PMID: 37943302. https://akjournals.com/view/journals/2060/aop/article-10.1556-2060.2023.00256/article-10.1556-2060.2023.00256.xml (Full text)

From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity

Abstract:

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. This mini-review navigates through the complex landscape of age-associated immune changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology of Long COVID. Immunosenescence serves as an introductory departure point, elucidating alterations in immune cell profiles and their functional dynamics, changes in T-cell receptor signaling, cytokine network dysregulation, and compromised regulatory T-cell function.

Subsequent scrutiny of chronic inflammation, or “inflammaging,” highlights its roles in age-related autoimmune susceptibilities and its potential as a mediator of the immune perturbations observed in Long COVID patients. The introduction of epigenetic facets further amplifies the potential interconnections.

In this compact review, we consider the dynamic interactions between immunosenescence, inflammation, and autoimmunity. We aim to explore the multifaceted relationships that link these processes and shed light on the underlying mechanisms that drive their interconnectedness. With a focus on understanding the immunological changes in the context of aging, we seek to provide insights into how immunosenescence and inflammation contribute to the emergence and progression of autoimmune disorders in the elderly and may serve as potential mediator for Long COVID disturbances.

Source: Müller L, Di Benedetto S. From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity. Front Immunol. 2023 Oct 24;14:1298004. doi: 10.3389/fimmu.2023.1298004. PMID: 37942323; PMCID: PMC10628127. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628127/ (Full text)

Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study

Abstract:

Post-COVID-19 condition (also known as long COVID) is a new, complex, and poorly understood disorder. A core outcome set (COS) for post-COVID-19 condition in adults has been developed and agreement is now required on the most appropriate measurement instruments for these core outcomes.

We conducted an international consensus study involving multidisciplinary experts and people with lived experience of long COVID. The study comprised a literature review to identify measurement instruments for the core outcomes, a three-round online modified Delphi process, and an online consensus meeting to generate a core outcome measurement set (COMS). 594 individuals from 58 countries participated.

The number of potential instruments for the 12 core outcomes was reduced from 319 to 19. Consensus was reached for inclusion of the modified Medical Research Council Dyspnoea Scale for respiratory outcomes. Measures for two relevant outcomes from a previously published COS for acute COVID-19 were also included: time until death, for survival, and the Recovery Scale for COVID-19, for recovery. Instruments were suggested for consideration for the remaining nine core outcomes: fatigue or exhaustion, pain, post-exertion symptoms, work or occupational and study changes, and cardiovascular, nervous system, cognitive, mental health, and physical outcomes; however, consensus was not achieved for instruments for these outcomes.

The recommended COMS and instruments for consideration provide a foundation for the evaluation of post-COVID-19 condition in adults, which should help to optimise clinical care and accelerate research worldwide. Further assessment of this COMS is warranted as new data emerge on existing and novel measurement instruments.

Source: Gorst SL, Seylanova N, Dodd SR, Harman NL, O’Hara M, Terwee CB, Williamson PR, Needham DM, Munblit D, Nicholson TR; PC-COS study group. Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study. Lancet Respir Med. 2023 Nov 2:S2213-2600(23)00370-3. doi: 10.1016/S2213-2600(23)00370-3. Epub ahead of print. PMID: 37926103. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00370-3/fulltext (Full text)

From COVID-19 to long COVID; the forms of the neurological manifestations

Abstract:

Ever since the SARS-CoV-2 infection was declared a global pandemic in 2020, numerous multisystemic manifestations have been discovered. The COVID-19 is known to cause a wide spectrum of neurological symptoms like fatigue, headache, brain fog, stroke, smell and taste disorders, encephalopathy and neurodegenerative disorders. The neurological manifestations are more prevalent in the post-COVID syndrome or long COVID. The National Institute for Health and Care Excellence and WHO defined Ongoing Symptomatic COVID as 4-12 weeks post infection and post COVID-19 syndrome as persistence of symptoms beyond 12 weeks.

So far there are limited data available regarding the pathophysiology of neurological symptoms of prolonged COVID, although neuroinflammation and oxidative damage have been implicated. In this review article, we have highlighted the transition from COVID to long-term COVID, focusing the discussion particularly on neurological complications.

Source: Ahuja, Sana and Zaheer, Sufian (2023) “From COVID-19 to long COVID; the forms of the neurological manifestations,” Journal of Mind and Medical Sciences: Vol. 10: Iss. 2, Article 5.
DOI: https://doi.org/10.22543/2392-7674.1403
Download available at: https://scholar.valpo.edu/jmms/vol10/iss2/5

The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

Abstract:

There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies.

Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity.

Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored.

Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.

Source: Li, J., Zhou, Y., Ma, J. et al. The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID. Sig Transduct Target Ther 8, 416 (2023). https://doi.org/10.1038/s41392-023-01640-z https://www.nature.com/articles/s41392-023-01640-z (Full text)

Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials

Abstract:

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.

Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.

Design: Systematic review of randomized controlled trials (RCTs).

Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies.

Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

Source: Yang J, Lim KH, Lim KT, Woods JT, Mohabbat AB, Wahner-Roedler DL, Ganesh R, Bauer BA. Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials. Ther Adv Chronic Dis. 2023 Oct 11;14:20406223231204727. doi: 10.1177/20406223231204727. PMID: 37841213; PMCID: PMC10571674. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571674/ (Full text)

Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms

Approximately one third of non-hospitalized coronavirus disease of 2019 (COVID-19) patients report chronic symptoms after recovering from the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some of the most persistent and common complaints of this post-acute COVID-19 syndrome (PACS) are cognitive in nature, described subjectively as “brain fog” and also objectively measured as deficits in executive function, working memory, attention, and processing speed. The mechanisms of these chronic cognitive sequelae are currently not understood.

SARS-CoV-2 inflicts damage to cerebral blood vessels and the intestinal wall by binding to angiotensin-converting enzyme 2 (ACE2) receptors and also by evoking production of high levels of systemic cytokines, compromising the brain’s neurovascular unit, degrading the intestinal barrier, and potentially increasing the permeability of both to harmful substances. Such substances are hypothesized to be produced in the gut by pathogenic microbiota that, given the profound effects COVID-19 has on the gastrointestinal system, may fourish as a result of intestinal post-COVID-19 dysbiosis. COVID-19 may therefore create a scenario in which neurotoxic and neuroinflammatory substances readily proliferate from the gut lumen and encounter a weakened neurovascular unit, gaining access to the brain and subsequently producing cognitive deficits.

Here, we review this proposed PACS pathogenesis along the gut-brain axis, while also identifying specific methodologies that are currently available to experimentally measure each individual component of the model.

Source: Plummer Allison M., Matos Yvette L., Lin Henry C., Ryman Sephira G., Birg Aleksandr, Quinn Davin K., Parada Alisha N., Vakhtin Andrei A. Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms. Frontiers in Neuroscience, Vol 17, 2023. DOI=10.3389/fnins.2023.1232480 ISSN=1662-453X  https://www.frontiersin.org/articles/10.3389/fnins.2023.1232480 (Full text)

Genomic communication via circulating extracellular vesicles and long-term health consequences of COVID-19

Abstract:

COVID-19 continues to affect an unprecedented number of people with the emergence of new variants posing a serious challenge to global health. There is an expansion of knowledge in understanding the pathogenesis of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of the acute disease on multiple organs. In addition, growing evidence reports that the impact of COVID-19 on different organs persists long after the recovery phase of the disease, leading to long-term consequences of COVID-19.

These long-term consequences involve pulmonary as well as extra-pulmonary sequelae of the disease. Noteably, recent research has shown a potential association between COVID-19 and change in the molecular cargo of extracellular vesicles (EVs). EVs are vesicles released by cells and play an important role in cell communication by transfer of bioactive molecules between cells. Emerging evidence shows a strong link between EVs and their molecular cargo, and regulation of metabolism in health and disease.

This review focuses on current knowledge about EVs and their potential role in COVID-19 pathogenesis, their current and future implications as tools for biomarker and therapeutic development and their possible effects on long-term impact of COVID-19.

Source: Nair, S., Nova-Lamperti, E., Labarca, G. et al. Genomic communication via circulating extracellular vesicles and long-term health consequences of COVID-19. J Transl Med 21, 709 (2023). https://doi.org/10.1186/s12967-023-04552-2 https://link.springer.com/article/10.1186/s12967-023-04552-2 (Full text)

 

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)