Long-term health consequences among individuals with SARS-CoV-2 infection compared to individuals without infection: results of the population-based cohort study CoMoLo Follow-up

Abstract:

Background: Most of the previous studies on health sequelae of COVID-19 are uncontrolled cohorts and include a relatively short follow-up. This population-based multi-center cohort study examined health consequences among individuals about 1 to 1.5 years after SARS-CoV-2 infection compared with non-infected.

Methods: The study population consisted of adults (≥ 18 years) from four municipalities particularly affected by the COVID-19 pandemic in the year 2020 who completed a detailed follow-up questionnaire on health-related topics. Exposure was the SARS-CoV-2 infection status (based on IgG antibodies, PCR test, or physician-diagnosis of COVID-19) at baseline (May to December 2020). Outcomes assessed at follow-up (October 2021 to January 2022; mean: 452 days) included recurrent or persistent health complaints, incident diseases, health-related quality of life (PROMIS-29), subjective health, and subjective memory impairment. Logistic and linear regression models were adjusted for baseline sociodemographic and lifestyle characteristics (age, sex, municipality, education, smoking, body mass index), pre-existing health conditions (chronic disease/health problem, health-related activity limitation, depressive/anxiety disorder), and follow-up time.

Results: Among 4817 participants, 350 had a SARS-CoV-2 infection at baseline and 4467 had no infection at baseline or during follow-up. Those with an infection statistically significantly more often reported 7 out of 18 recurrent or persistent health complaints at follow-up: smell/taste disorders (12.8% vs. 3.4%, OR 4.11), shortness of breath (23.0% vs. 9.5%, 3.46), pain when breathing (4.7% vs. 1.9%, 2.36), fatigue (36.9% vs. 26.1%, 1.76), weakness in legs (12.8% vs. 7.8%, 1.93), myalgia/joint pain (21.9% vs. 15.1%, 1.53) and cough (30.8% vs. 24.8%, 1.34) and 3 out of 6 groups of incident diseases: liver/kidney (2.7% vs. 0.9%, 3.70), lung (3.2% vs. 1.1%, 3.50) and cardiovascular/metabolic (6.5% vs. 4.0%, 1.68) diseases. Those with an infection were significantly more likely to report poor subjective health (19.3% vs. 13.0%, 1.91), memory impairment (25.7% vs. 14.3%, 2.27), and worse mean scores on fatigue and physical function domains of PROMIS-29 than non-infected.

Conclusion: Even after more than one year, individuals with SARS-CoV-2 infection showed an increased risk of various health complaints, functional limitations, and worse subjective well-being, pointing toward profound health consequences of SARS-CoV-2 infection relevant for public health.

Source: Heidemann C, Sarganas G, Du Y, Gaertner B, Poethko-Müller C, Cohrdes C, Schmidt S, Schlaud M, Scheidt-Nave C. Long-term health consequences among individuals with SARS-CoV-2 infection compared to individuals without infection: results of the population-based cohort study CoMoLo Follow-up. BMC Public Health. 2023 Aug 21;23(1):1587. doi: 10.1186/s12889-023-16524-8. PMID: 37605232; PMCID: PMC10440884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440884/ (Full text)

Forming a consensus opinion to inform long COVID support mechanisms and interventions: a modified Delphi approach

Abstract:

Background: Current approaches to support patients living with post-COVID condition, also known as Long COVID, are highly disparate with limited success in managing or resolving a well-documented and long-standing symptom burden. With approximately 2.1 million people living with the condition in the UK alone and millions more worldwide, there is a desperate need to devise support strategies and interventions for patients.

Methods: A three-round Delphi consensus methodology was distributed internationally using an online survey and was completed by healthcare professionals (including clinicians, physiotherapists, and general practitioners), people with long COVID, and long COVID academic researchers (round 1 n = 273, round 2 n = 186, round 3 n = 138). Across the three rounds, respondents were located predominantly in the United Kingdom (UK), with 17.3-15.2% (round 1, n = 47; round 2 n = 32, round 2 n = 21) of respondents located elsewhere (United States of America (USA), Austria, Malta, United Arab Emirates (UAE), Finland, Norway, Malta, Netherlands, Iceland, Canada, Tunisie, Brazil, Hungary, Greece, France, Austrailia, South Africa, Serbia, and India). Respondents were given ∼5 weeks to complete the survey following enrolment, with round one taking place from 02/15/2022 to 03/28/22, round two; 05/09/2022 to 06/26/2022, and round 3; 07/14/2022 to 08/09/2022. A 5-point Likert scale of agreement was used and the opportunity to include free text responses was provided in the first round.

Findings: Fifty-five statements reached consensus (defined as >80% agree and strongly agree), across the domains of i) long COVID as a condition, ii) current support and care available for long COVID, iii) clinical assessments for long COVID, and iv) support mechanisms and rehabilitation interventions for long COVID, further sub-categorised by consideration, inclusion, and focus. Consensus reached proposes that long COVID requires specialised, comprehensive support mechanisms and that interventions should form a personalised care plan guided by the needs of the patients. Supportive approaches should focus on individual symptoms, including but not limited to fatigue, cognitive dysfunction, and dyspnoea, utilising pacing, fatigue management, and support returning to daily activities. The mental impact of living with long COVID, tolerance to physical activity, emotional distress and well-being, and research of pre-existing conditions with similar symptoms, such as myalgic encephalomyelitis, should also be considered when supporting people with long COVID.

Interpretation: We provide an outline that achieved consensus with stakeholders that could be used to inform the design and implementation of bespoke long COVID support mechanisms.

Source: Owen R, Ashton REM, Ferraro FV, Skipper L, Bewick T, Leighton P, Phillips BE, Faghy MA. Forming a consensus opinion to inform long COVID support mechanisms and interventions: a modified Delphi approach. EClinicalMedicine. 2023 Aug 9;62:102145. doi: 10.1016/j.eclinm.2023.102145. PMID: 37599906; PMCID: PMC10432807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432807/ (Full text)

The effect of long-haul COVID-19 toward domains of the health-related quality of life among recovered hospitalized patients

Abstract:

Background: People with long-haul COVID-19 could experience various health problems, from mild to severe. This research aimed to identify the effect of long-haul COVID-19, specifically on the Quality-of-Life domains experienced by COVID-19 patients who have been discharged.

Methods: Data collection was done online, using data from DKI Jakarta hospitalized patients confirmed with and recovered from SARS-CoV-2 infections. We selected patients who have a minimum of 28 days after being hospitalized for COVID-19 positive. The Logistic regression technique was used to analyze the data. The questionnaire used in this research contained questions regarding long-haul COVID-19 symptoms and domains of Quality of Life, which WHOQOL-BREF measured. Before collecting data, we tested the questionnaire with 30 recovered patients hospitalized outside DKI Jakarta.

Results: 172 recovered inpatients who filled out the questionnaire correctly and were aged 18 years and above were randomly selected. Almost one-third (30.2%) of the recovered inpatients had long-haul COVID-19, with 23.8% experiencing one long-haul symptom and 6.4% experiencing more than one symptom. This research also showed that the long-haul effects of COVID-19 affected almost all domains of Quality of Life except the environmental one. Age, gender, and marital status were covariates for the association between long-haul COVID-19 and The Quality of Life.

Conclusion: Continuing health services after the patient is discharged from the hospital is an important program for COVID-19 survivors because it can prevent a decline in the Quality of Life among patients due to the long-haul COVID-19.

Source: Trihandini I, Muhtar M, Karunia Sakti DA, Erlianti CP. The effect of long-haul COVID-19 toward domains of the health-related quality of life among recovered hospitalized patients. Front Public Health. 2023 Aug 3;11:1068127. doi: 10.3389/fpubh.2023.1068127. PMID: 37601220; PMCID: PMC10434763. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10434763/ (Full text)

Compounding for the Treatment of COVID-19 and Long COVID, Part 4: The Legacy of Chronic COVID

Abstract:

People infected by severe acute respiratory coronavirus 2 (SARS-CoV-2) risk the development of not only acute coronavirus- disease-2019 (COVID-19) – the signs and symptoms of which range from none to severe illness that requires intensive treatment – but also long COVID (i.e., chronic COVID), a cyclical, progressive, multiphasic illness characterized by myriad debilitating conditions that persist long term. In some patients, those sequelae result in psychiatric disorders that can lead to suicide or other forms of self-harm, incidences of which have increased exponentially since before the COVID pandemic. It has been suggested that long COVID develops in an estimated 10% to 35% of people diagnosed as having COVID-19.

Because the success of therapy for either form of COVID can be complicated by each patient’s pharmacogenomic profile, personal treatment preferences, medical needs, and/or dosing requirements, we have found that in some people so afflicted, manufactured medications are ineffective or intolerable, and that for those individuals, a customized compound often provides relief and promotes recovery. The primary focus of this article is long COVID. The pathogenesis of that disease is reviewed, therapies for the signs and symptoms it engenders are examined, and 2 compounded formulations effective in treating both acute and chronic COVID-19 are presented.

Source: Riepl M, Kaiser J. Compounding for the Treatment of COVID-19 and Long COVID, Part 4: The Legacy of Chronic COVID. Int J Pharm Compd. 2023 Jul-Aug;27(4):284-293. PMID: 37595172. https://pubmed.ncbi.nlm.nih.gov/37595172/

Predictors of Post-COVID-19 Functional Status Scale in hospitalized patients recovering from SARS-CoV-2 infection

Abstract:

Objective: The study aimed to investigate whether peripheral and inspiratory muscle strength and architecture, functional capacity, functional mobility, fatigue and health-related quality of life (HRQoL) are predictors of the PCFS scale score in patients with post-COVID-19 syndrome who were hospitalized.

Design: A cross-sectional study included 69 patients (53.3 ± 13.2 years, 36 men) with post-COVID-19 syndrome. The following outcomes were assessed: peripheral (dynamometry) and inspiratory (manovacuometry) muscle strength, muscle architecture (ultrasound), functional capacity (six-minute walk test), functional mobility (Timed Up and Go), fatigue (Functional Assessment of Chronic Illness Therapy), HRQoL (36-item Short Form Health Survey) and functional status (PCFS scale).

Results: Functional mobility (β = 0.573; P < 0.001), vastus intermedius echogenicity (β = -0.491; P = 0.001), length of stay (β = 0.349; P = 0.007) and female sex (β = 0.415; P = 0.003) influenced the PCFS scale.

Conclusion: Functional mobility, muscle quality of the vastus intermedius, length of stay and female sex influence the PCFS scale score in this population. It is noteworthy that functional mobility is an independent predictor of PCFS scale.

Source: Dos Santos TD, Alves Souza J, Cardoso DM, Berni VB, Pasqualoto AS, de Albuquerque IM. Predictors of Post-COVID-19 Functional Status Scale in hospitalized patients recovering from SARS-CoV-2 infection. Am J Phys Med Rehabil. 2023 Aug 18. doi: 10.1097/PHM.0000000000002325. Epub ahead of print. PMID: 37594212. https://pubmed.ncbi.nlm.nih.gov/37594212/

The Long Covid-19 Syndrome the Spike Protein and Stem Cells, the Underrated Role of Retrotransposons, a Working Hypothesis

Abstract

Coronavirus disease-2019 (COVID-19) was seen as a respiratory disease, however, an increasing number of reports indicated that the spike protein could also be the cause of the long-term post-infectious conditions known as Long-COVID characterized by a group of unresponsive idiopathic severe neuro, cardio-vascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Parkinson’s like-disease. Different lines of pieces of evidence confirmed that the spike protein that can be found on the surface of the SARS-CoV-2 virus latches onto angiotensin-converting enzyme 2 (ACE2) receptors located on target cells.
The RNA genome of coronaviruses, which, has a median length of 29 kb and is the longest among all RNA viruses, is comprised of six to ten open reading frames (ORFs) that are responsible for encoding both the replicase and structural proteins for the virus. Each of the components of the viral genome is packaged into a helical nucleocapsid that is surrounded by a lipid bilayer. The viral envelope of coronaviruses is typically made up of three proteins that include the membrane protein (M), the envelope protein (E), and the spike protein (S). The spike protein not only facilitates the virus entry into healthy cells, which is the first step in infection but also promote profound damage to different organs and tissues leading to severe impairments and long-term disabilities.
Here, we discussed the pervasive mechanism that spikes mRNA adopted to alter multipotent and pluripotent stem cell (SCs) genomes and the acquired disability of generating an infinite number of affected clonal cells. This stance is based on the molecular and evolutionary aspects obtained from retrotransposons-retrotransposition in mammalians and humans that documented the frequent integration of mRNA molecules into genomes and thus into DNA. Retrotransposition is the molecular process in which transcribed and spliced mRNAs are accidentally reverse-transcribed and inserted into new genomic positions to form a retrogene.
Sequence-specific traits of mRNA clearly showed long interspersed element-1 (LINE-1 or L1) to confirm the retrotransposition, considered the most abundant autonomously active retrotransposons in the human genome. In mammals, L1 retrotransposons drive retrotransposition and are composed of long terminal repeats (LTRs) and non-LTR retrotransposons (mainly long interspersed nuclear elements or LINEs); specifically, the LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons.
In response to retrotransposons transposition, stem cells (SCs) employ a number of silencing mechanisms, such as DNA methylation and histone modification. This manuscript theorizes the expression patterns, functions, and regulation of mRNA Spike protein imprinted by SCs retrotransposons which generate unlimited lines of affected cell progenies and tissues as the main condition of untreatable Spike-related inflammatory conditions.
Source: Balzanelli, M.G.; Distratis, P.; Lazzaro, R.; Dipalma, G.; Inchingolo, F.; Del Prete, R.; Hung Pham, V.; Aityan, S.K.; Nguyen, K.C.; Isacco Gargiulo, C. The Long Covid-19 Syndrome the Spike Protein and Stem Cells, the Underrated Role of Retrotransposons, a Working Hypothesis. Preprints 2023, 2023081130. https://doi.org/10.20944/preprints202308.1130.v1 https://www.preprints.org/manuscript/202308.1130/v1 (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)

Long Covid requires a global response centred on equity and dialogue

Abstract:

Long Covid, or Post-Covid Conditions, is a global health problem. Yet we know strikingly little about the different experiences of Long Covid patients cross-nationally. To address this shortcoming, we conducted an online survey of Long Covid patients active on social media in the U.S. (n = 334, October to December 2021) and Brazil (n = 144, January to April 2022). Our analysis of short answer responses indicates patient dissatisfaction with medical care provided for Long Covid in both the U.S. and Brazil. For Long Covid patients in Brazil, there were additional concerns raised about the lack of local expertise about their condition.

Based on these results, we urge policymakers to expand the education of medical professionals in order to raise awareness of Long Covid. Experts in the Global North should also be encouraged to engage in dialogue with patient groups and experts in the Global South, in order to better understand how local contexts shape the experience of Long Covid.

Source: Au L, Capotescu C, Curi A, Gonçalves Leonel da Silva R, Eyal G. Long Covid requires a global response centred on equity and dialogue. Glob Health Action. 2023 Dec 31;16(1):2244757. doi: 10.1080/16549716.2023.2244757. PMID: 37581581; PMCID: PMC10431739. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431739/ (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)