Tag: long covid review

SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)

Abstract:

Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a ‘reservoir’. This reservoir could modulate host immune responses or release viral proteins into the circulation.

Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.

Source: Proal AD, VanElzakker MB, Aleman S, Bach K, Boribong BP, Buggert M, Cherry S, Chertow DS, Davies HE, Dupont CL, Deeks SG, Eimer W, Ely EW, Fasano A, Freire M, Geng LN, Griffin DE, Henrich TJ, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter MM, Peluso MJ, Pretorius E, Price DA, Putrino D, Scheuermann RH, Tan GS, Tanzi RE, VanBrocklin HF, Yonker LM, Wherry EJ. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat Immunol. 2023 Sep 4. doi: 10.1038/s41590-023-01601-2. Epub ahead of print. PMID: 37667052. https://www.nature.com/articles/s41590-023-01601-2 (Full text)

Long Covid & Antidepressants

Abstract:

Three years into this historic pandemic, the scientific and healthcare communities continue to learn agreat deal regarding COVID-19, the disease that is produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most urgent and immediate focus has been on vaccine development for diseaseprevention/mitigation and on identification of effective therapeutic interventions for acute phase of illness. However, attention is increasingly being placed on formulating treatment strategies for individuals who arepost-COVID-19 and experiencing a syndrome of persistent cognitive, somatic and behavioral symptoms that is being referred to as long COVID.

In addition to identifying novel compounds that may improve outcome ineither acute or residual COVID-19, an alternate and parallel strategy is to repurpose or reposition drugs which have been approved for other conditions and subsequently assess their safety and efficacy when applied toCOVID-19. In this light, antidepressant medications, particularly serotonin reuptake inhibitors, have garnered attention amidst evidence supporting their anti-inflammatory and anti-viral properties. Results from several preliminary studies suggest that early administration of antidepressants may prevent clinical deterioration and even death in patients with acute COVID-19.

In this article, we present purported anti-inflammatory mechanisms of the antidepressants, review results from studies that have appeared in the literature to date regarding antidepressants and acute COVID-19, and discuss the possible utility of antidepressants as a potential therapeutic resource for long COVID.

Source: Rivas-Vázquez R, Carrazana EJ, Blais MA, Rey GJ, Rivas-Vázquez E. Long Covid & Antidepressants. Med Discoveries. 2023; 2(3): 1023.  https://meddiscoveries.org/pdf/1023.pdf (Full text)

Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review

Summary:

  • Neurological symptoms are not uncommon during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reflect a broad spectrum of neurological disorders of which clinicians should be aware.
  • The underlying pathogenesis of neurological disease in coronavirus disease 2019 (COVID-19) may be due to four mechanisms of nervous system dysfunction and injury: i) direct viral neurological invasion; ii) immune dysregulation; iii) endothelial dysfunction and coagulopathy; and iv) severe systemic COVID-19 disease.
  • Neurological manifestations of acute COVID-19 include headache, peripheral neuropathies, seizures, encephalitis, Guillain–Barré syndrome, and cerebrovascular disease.
  • Commonly reported long term neurological sequelae of COVID-19 are cognitive dysfunction and dysautonomia, which despite being associated with severe acute disease are also seen in people with mild disease.
  • Assessment of cognitive dysfunction after COVID-19 is confounded by a high prevalence of comorbid fatigue, anxiety, and mood disorders. However, other markers of neuroaxonal breakdown suggest no significant neuronal injury apart from during severe acute COVID-19.
  • The long term impact of COVID-19 on neurological diseases remains uncertain and requires ongoing vigilance.

Source: Wesselingh, R. (2023), Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review. Med J Aust. https://doi.org/10.5694/mja2.52063 https://onlinelibrary.wiley.com/doi/10.5694/mja2.52063 (Full text available as PDF file)

 

Pathophysiology, diagnosis, and management of neuroinflammation in covid-19

Abstract:

Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome.

Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up.

Source: Brown R L, Benjamin L, Lunn M P, Bharucha T, Zandi M S, Hoskote C et al. Pathophysiology, diagnosis, and management of neuroinflammation in covid-19 BMJ 2023; 382 :e073923 doi:10.1136/bmj-2022-073923 https://www.bmj.com/content/382/bmj-2022-073923.abstract (Full text available as PDF file)

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/