Post-COVID-19 Symptoms in Adults with Asthma—Systematic Review

Abstract:

Background: Research on the longer-term sequelae of COVID-19 in patients with asthma is limited. Objective: To assess the frequency and severity of long-term symptoms of COVID-19 in the population of asthma patients.
Methods: A systematic review of the published literature was conducted in accordance with the recommendations of the PRISMA statement. EMBASE, MEDLINE/PubMed, Web of Science, CINAHL, and Scopus Scholar were searched for terms related to asthma and post or long COVID-19, and for systematic reviews related to specific questions within our review, up to June 2022.
Results: Data from 9 references publications included in the review were extracted. A total of 1466 adult asthmatic patients with COVID-19 infection were described in all the publications mentioned above. Of the long-term symptoms reported after COVID-19, patients indicated: lower respiratory symptoms, fatigue, cognitive symptoms, psychological problems, and other such as skin rashes, gastrointestinal disorders, tachycardia, palpitations, ocular disorders, ageusia/hypogeusia, anosmia/hyposmia, and poor sleep quality. These symptoms in similar intensity were observed in the comparison groups without a diagnosis of asthma.
Conclusions: The published data neither confirm nor deny that long-term COVID-19 symptoms in patients with asthma diagnosis are different in strength and frequency from patients without asthma diagnosis. To indicate associations between asthma and COVID-19 infection and severity, as well as the frequency of long-term symptoms of COVID-19, more longitudinal research is needed in chronic asthma patients with different phenotypes, intensity of treatment, and degree of asthma control.
Source: Kaszuba M, Madej N, Pilinski R, Sliwka A. Post-COVID-19 Symptoms in Adults with Asthma—Systematic Review. Biomedicines. 2023; 11(8):2268. https://doi.org/10.3390/biomedicines11082268 https://www.mdpi.com/2227-9059/11/8/2268 (Full text)

Cocreation of Assistive Technologies for Patients With Long COVID: Qualitative Analysis of a Literature Review on the Challenges of Patient Involvement in Health and Nursing Sciences

Abstract:

Background: Digital assistive technologies have the potential to address the pressing need for adequate therapy options for patients with long COVID (also known as post-COVID-19 condition) by enabling the implementation of individual and independent rehabilitation programs. However, the involvement of the target patient group is necessary to develop digital devices that are closely aligned to the needs of this particular patient group.

Objective: Participatory design approaches, such as cocreation, may be a solution for achieving usability and user acceptance. However, there are currently no set methods for implementing cocreative development processes incorporating patients. This study addresses the following research questions: what are the tasks and challenges associated with the involvement of patient groups? What lessons can be learned regarding the adequate involvement of patients with long COVID?

Methods: First, a literature review based on a 3-stage snowball process was conducted to identify the tasks and challenges emerging in the context of the cocreation of digital assistive devices and services with patient groups. Second, a qualitative analysis was conducted in an attempt to extract relevant findings and criteria from the identified studies. Third, using the method of theory adaptation, this paper presents recommendations for the further development of the existing concepts of cocreation in relation to patients with long COVID.

Results: The challenges of an active involvement of patients in cocreative development in health care include hierarchical barriers and differences in the levels of specific knowledge between professionals and patients. In the case of long COVID, patients themselves are still inexperienced in dealing with their symptoms and are hardly organized into established groups. This amplifies general hurdles and leads to questions of group identity, power structure, and knowledge creation, which are not sufficiently addressed by the current methods of cocreation.

Conclusions: The adaptation of transdisciplinary methods to cocreative development approaches focusing on collaborative and inclusive communication can address the recurring challenges of actively integrating patients with long COVID into development processes.

Source: Dalko K, Kraft B, Jahn P, Schildmann J, Hofstetter S. Cocreation of Assistive Technologies for Patients With Long COVID: Qualitative Analysis of a Literature Review on the Challenges of Patient Involvement in Health and Nursing Sciences. J Med Internet Res. 2023 Aug 15;25:e46297. doi: 10.2196/46297. PMID: 37581906. https://www.jmir.org/2023/1/e46297 (Full text)

Post-COVID-19 syndrome management: Utilizing the potential of dietary polysaccharides

Abstract:

The COVID-19 pandemic has caused significant global impact, resulting in long-term health effects for many individuals. As more patients recover, there is a growing need to identify effective management strategies for ongoing health concerns, such as post-COVID-19 syndrome, characterized by persistent symptoms or complications beyond several weeks or months from the onset of symptoms. In this review, we explore the potential of dietary polysaccharides as a promising approach to managing post-COVID-19 syndrome.

We summarize the immunomodulatory, antioxidant, antiviral, and prebiotic activities of dietary polysaccharides for the management of post-COVID-19 syndrome. Furthermore, the review investigates the role of polysaccharides in enhancing immune response, regulating immune function, improving oxidative stress, inhibiting virus binding to ACE2, balancing gut microbiota, and increasing functional metabolites. These properties of dietary polysaccharides may help alleviate COVID-19 symptoms, providing a promising avenue for effective treatment strategies.

Source: Cheong KL, Yu B, Teng B, Veeraperumal S, Xu B, Zhong S, Tan K. Post-COVID-19 syndrome management: Utilizing the potential of dietary polysaccharides. Biomed Pharmacother. 2023 Aug 16;166:115320. doi: 10.1016/j.biopha.2023.115320. Epub ahead of print. PMID: 37595427. https://www.sciencedirect.com/science/article/pii/S0753332223011113 (Full text)

Experimental drugs in randomized controlled trials for long-COVID: what’s in the pipeline? A systematic and critical review

Article highlights:

  • Presently, no standard treatment exists for long-COVID, a post-coronavirus disease 2019 (COVID-19) syndrome, characterized by symptoms such as fatigue and brain fog lasting for 3 months or more after acute COVID-19.
  • Owing to increased funding, increasing numbers of randomized controlled trials (RCTs) on drug treatments for long-COVID are being conducted. We systematically and critically reviewed these RCTs to pinpoint drugs with high potential for treating long-COVID.
  • Of the four completed RCTs identified, three examined long-COVID prevention, of which only metformin was deemed to exhibit high potential in preventing long-COVID when administered during acute COVID-19. Only one RCT investigated the potential efficacy of a drug (Treamid) in treating ongoing long-COVID, showing low to modest potential due to its inefficacy in improving the more meaningful outcomes of long-COVID.
  • Of the 22 ongoing RCTs identified, only rintatolimod and LYT-100 (deupirfenidone) were judged as possessing modest to high potential for treating long-COVID.
  • The fact that nearly all of the drug candidates did not seem to exhibit high potential in treating long-COVID is a testament to the ordeal of treating long-COVID.
  • Given that long-COVID is a multifaceted condition with multiple proposed subtypes, its treatment may need to be tailored to specific subtypes.

Abstract:

Introduction: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID.

Areas covered: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.

Expert opinion: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.

Source: Yong SJ, Halim A, Halim M, Ming LC, Goh KW, Alfaresi M, AlShehail BM, Al Fares MA, Alissa M, Sulaiman T, Alsalem Z, Alwashmi ASS, Khamis F, Al Kaabi NA, Albayat H, Alsheheri A, Garout M, Alsalman J, Alfaraj AH, Alhajri M, Dhama K, Alburaiky LM, Alsanad AH, AlShurbaji AT, Rabaan AA. Experimental drugs in randomized controlled trials for long-COVID: what’s in the pipeline? A systematic and critical review. Expert Opin Investig Drugs. 2023 Aug 4:1-13. doi: 10.1080/13543784.2023.2242773. Epub ahead of print. PMID: 37534972. https://pubmed.ncbi.nlm.nih.gov/37534972/

Myocarditis and Myocardial Injury in Long COVID Syndrome: A Comprehensive Review of the Literature

Abstract:

The repercussions of coronavirus disease 2019 (COVID-19) have been devastating on a global scale. Long COVID, which affects patients for weeks or even months after their initial infection, is not limited to individuals with severe symptoms and can affect people of all ages. The condition can impact various physiological systems, leading to chronic health conditions and long-term disabilities that present  significant challenges for healthcare systems worldwide.

This review explores the link between long COVID and cardiovascular complications such as myocardial injury and myocarditis. It also highlights the prevalence of these complications and identifies risk factors for their development in long COVID patients.

Myocardial injury occurs due to direct cellular damage and T-cell-mediated cytotoxicity resulting in elevated cardiac biomarkers. Diagnostic techniques like electrocardiogram, troponin level testing, and magnetic resonance imaging can help identify myocarditis, but endomyocardial biopsy is considered the goldstandard diagnostic technique.

Guideline-directed medical therapy is recommended for COVID-19 myocarditis patients for better prognosis while being monitored under comprehensive care management approaches. Therefore, it’s critical to develop effective screening techniques specifically for vulnerable populations while conducting further research that addresses the effects of long COVID on society’s physical health.

Source: Paruchuri S, Farwa U, Jabeen S, et al. (July 25, 2023) Myocarditis and Myocardial Injury in Long COVID Syndrome: A Comprehensive Review of the Literature. Cureus 15(7): e42444. DOI 10.7759/cureus.42444 https://assets.cureus.com/uploads/review_article/pdf/162949/20230725-18887-1iha61y.pdf (Full text as PDF file)

A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population

Abstract:

Context: Long-term health effects after coronavirus disease 2019 (COVID-19) have been increasingly reported but their prevalence and significance in the pediatric population remains uncertain.

Objective: To present the prevalence and characteristics of the long-term clinical features of COVID-19 (long COVID) in the global pediatric population.

Data sources: PubMed, Embase, Web of Science, Cochrane Library, WHO COVID-19 database, google scholar, medRxiv, bioRxiv, and multiple national public health databases.

Study selection: Published articles and preprints from December, 2019 to December, 2022 investigating the epidemiology and characteristics of persistent clinical features at least 3 months after COVID-19 in children and adolescents (0-19 years old) were included.

Data extraction: Study characteristics and detailed description of long COVID were extracted into a predefined form.

Results: Twenty seven cohorts and 4 cross-sectional studies met the inclusion criteria and involved over 15 000 pediatric participants. A total of more than 20 persistent symptoms and clinical features were reported among children and adolescents. 16.2% (95% confidence interval 8.5% to 28.6%) of the pediatric participants experienced 1 or more persistent symptom(s) at least 3 months post COVID-19. Female gender might be associated with developing certain long COVID symptoms.

Limitations: Included studies presented with great heterogeneity because of significant variations in the definition of “long COVID,” follow up duration, and method. There could be nonresponse and other potential bias.

Conclusions: Persistent clinical features beyond 3 months among children and adolescents with proven COVID-19 are common and the symptom spectrum is wide. High-quality, prospective studies with proper controls are necessary in the future.

Source: Jiang L, Li X, Nie J, Tang K, Bhutta ZA. A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population. Pediatrics. 2023 Aug 1;152(2):e2022060351. doi: 10.1542/peds.2022-060351. PMID: 37476923; PMCID: PMC10389775. https://pubmed.ncbi.nlm.nih.gov/37476923/

Culinary spices and herbs in managing early and long-COVID-19 complications: A comprehensive review

Abstract:

Human race is preparing for the upsurge and aftermath of COVID-19 pandemic complicated by novel variants, new waves, variable mortality rate, and post-COVID complications. Despite use of repurposed drugs, symptomatic treatments and licensing of multiple vaccines, the daily number of cases and rate of transmission are significant. Culinary spices and herbs have been historically used in pandemic and non-pandemic times to reduce respiratory viral burden. Specific food items and culinary spices can boost the levels of protective immunity and also offer therapeutic benefits against impervious bugs via well-known as well as less-known but scientifically testable mechanisms.

Here, we analyzed the phytochemicals profile of Ayurvedic herbs and inferred from the clinical trials/observational studies to provide a focused and succinct perspective on the relevance of “food-based” traditional decoction to moderate COVID-19 disease and long-COVID via modulation of immunity and reinstatement of homeostasis. We also underscore the druggable targets in pathogenesis of COVID-19 which are relevant to the ongoing clinical trials using spices and herbs. This information will provide a strong scientific rationale for standardization of the traditional herbs-based therapies and adopting the use of herbs, spices, and their formulations for reducing SARS-CoV-2 transmission, long-COVID symptoms, and COVID-19 disease progression.

Source: Maurya DK, Sharma D. Culinary spices and herbs in managing early and long-COVID-19 complications: A comprehensive review. Phytother Res. 2023 Jul 19. doi: 10.1002/ptr.7957. Epub ahead of print. PMID: 37468320. https://pubmed.ncbi.nlm.nih.gov/37468320/

Consistency of inconsistency in long-COVID-19 pain symptoms persistency: A systematic review and meta-analysis

Abstract:

Introduction: Individuals recovering from acute COVID-19 episodes may continue to suffer from various ongoing symptoms, collectively referred to as Long-COVID. Long-term pain symptoms are amongst the most common and clinically significant symptoms to be reported for this post-COVID-19 syndrome.

Objectives: This systematic review and meta-analysis aimed to evaluate the proportions of persisting pain symptoms experienced by individuals past the acute phase of COVID-19 and to identify their associated functional consequences and inflammatory correlates.

Methods: Two online databases were systematically searched from their inception until 31 March 2022. We searched primary research articles in English, which evaluated individuals after laboratory-confirmed COVID-19 acute phase resolution and specifically reported on pain symptoms and their inflammatory and/or functional outcomes.

Results: Of the 611 identified articles, 26 were included, used for data extraction, and assessed for their methodological quality and risk of bias by two independent reviewers. Pain symptoms were grouped under one of six major pain domains, serving as our primary co-outcomes. Proportional meta-analyses of pooled logit-transformed values of single proportions were performed using the random-effects-restricted maximum-likelihood model. An estimated 8%, 6%, 18%, 18%, 17%, and 12% of individuals continued to report the persistence of chest, gastrointestinal, musculoskeletal joint, musculoskeletal muscle, general body, and nervous system-related pain symptoms, respectively, for up to one year after acute phase resolution of COVID-19. Considerable levels of heterogeneity were demonstrated across all results. Functional and quality-of-life impairments and some inflammatory biomarker elevations were associated with the persistence of long-COVID pain symptoms.

Conclusion: This study’s findings suggest that although not well characterized, long-COVID pain symptoms are being experienced by non-negligible proportions of those recovering from acute COVID-19 episodes, thus highlighting the importance of future research efforts to focus on this aspect.

Source: Kerzhner O, Berla E, Har-Even M, Ratmansky M, Goor-Aryeh I. Consistency of inconsistency in long-COVID-19 pain symptoms persistency: A systematic review and meta-analysis. Pain Pract. 2023 Jul 21. doi: 10.1111/papr.13277. Epub ahead of print. PMID: 37475709. https://onlinelibrary.wiley.com/doi/10.1111/papr.13277 (Full study)

Persistent post-COVID-19 neuromuscular symptoms

Abstract:

Neuromuscular symptoms may develop or persist after resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides residual sensorimotor symptoms associated with acute neuromuscular complications of coronavirus disease-2019 (COVID-19), such as Guillain-Barré syndrome, critical illness neuromyopathy, and rhabdomyolysis, patients may report persistent autonomic symptoms, sensory symptoms, and muscle symptoms in the absence of these acute complications, including palpitations, orthostatic dizziness and intolerance, paresthesia, myalgia, and fatigue.

These symptoms may be associated with long COVID, also known as post-COVID-19 conditions or postacute sequelae of SARS-CoV-2 infection, which may significantly impact quality of life. Managing these symptoms represents a challenge for health-care providers.

Recent advances have identified small-fiber neuropathy as a potential etiology that may underlie autonomic dysfunction and paresthesia in some long COVID patients. The pathogenic mechanisms underlying myalgia and fatigue remain elusive and need to be investigated. Herein we review the current state of knowledge regarding the evaluation and management of patients with persistent post-COVID-19 neuromuscular symptoms.

Source: Abrams RMC, Zhou L, Shin SC. Persistent post-COVID-19 neuromuscular symptoms. Muscle Nerve. 2023 Jul 19. doi: 10.1002/mus.27940. Epub ahead of print. PMID: 37466117. https://onlinelibrary.wiley.com/doi/10.1002/mus.27940 (Full text)

Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post‐COVID‐19 condition

Abstract:

Background: The post-COVID-19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that ‘microclots’ cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term ‘microclots’ is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID-19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC.

Objectives: Laboratory studies review To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. Randomized controlled trials review To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials.

Search methods: Laboratory studies review We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms ‘COVID’, ‘amyloid’, ‘fibrin’, ‘fibrinogen’. Randomized controlled trials review We searched the following databases on 21 October 2022: Cochrane COVID-19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress.

Selection criteria: Laboratory studies review Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls. Randomized controlled trials review Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC.

Data collection and analysis: Two review authors applied study inclusion criteria to identify eligible studies and extracted data. Laboratory studies review We assessed the risk of bias of included studies using pre-developed methods for laboratory studies. We planned to perform synthesis without meta-analysis (SWiM) as described in our protocol. Randomized controlled trials review We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post-COVID-19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind).

Main results: Laboratory studies review We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls. Randomized controlled trials review We identified no trials meeting our inclusion criteria.

Authors’ conclusions: In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well-conducted randomized controlled trial.

Source: Fox T, Hunt BJ, Ariens RA, Towers GJ, Lever R, Garner P, Kuehn R. Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition. Cochrane Database Syst Rev. 2023 Jul 26;7(7):CD015775. doi: 10.1002/14651858.CD015775. PMID: 37491597; PMCID: PMC10368521. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368521/ (Full text)