Tag: 2022

LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION): protocol for a mixed-methods study in the UK

Abstract:

Introduction: Long COVID, a new condition whose origins and natural history are not yet fully established, currently affects 1.5 million people in the UK. Most do not have access to specialist long COVID services. We seek to optimise long COVID care both within and outside specialist clinics, including improving access, reducing inequalities, helping self-management and providing guidance and decision support for primary care. We aim to establish a ‘gold standard’ of care by systematically analysing current practices, iteratively improving pathways and systems of care.

Methods and analysis: This mixed-methods, multisite study is informed by the principles of applied health services research, quality improvement, co-design, outcome measurement and learning health systems. It was developed in close partnership with patients (whose stated priorities are prompt clinical assessment; evidence-based advice and treatment and help with returning to work and other roles) and with front-line clinicians. Workstreams and tasks to optimise assessment, treatment and monitoring are based in three contrasting settings: workstream 1 (qualitative research, up to 100 participants), specialist management in 10 long COVID clinics across the UK, via a quality improvement collaborative, experience-based co-design and targeted efforts to reduce inequalities of access, return to work and peer support; workstream 2 (quantitative research, up to 5000 participants), patient self-management at home, technology-supported monitoring and validation of condition-specific outcome measures and workstream 3 (quantitative research, up to 5000 participants), generalist management in primary care, harnessing electronic record data to study population phenotypes and develop evidence-based decision support, referral pathways and analysis of costs. Study governance includes an active patient advisory group.

Ethics and dissemination: LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS study is sponsored by the University of Leeds and approved by Yorkshire & The Humber-Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Participants will provide informed consent. Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers.

Source: Sivan M, Greenhalgh T, Darbyshire JL, Mir G, O’Connor RJ, Dawes H, Greenwood D, O’Connor D, Horton M, Petrou S, de Lusignan S, Curcin V, Mayer E, Casson A, Milne R, Rayner C, Smith N, Parkin A, Preston N, Delaney B; LOCOMOTION consortium. LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION): protocol for a mixed-methods study in the UK. BMJ Open. 2022 May 17;12(5):e063505. doi: 10.1136/bmjopen-2022-063505. PMID: 35580970; PMCID: PMC9114312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114312/ (Full text)

Long COVID – One Year On

Abstract:

Long COVID is now a recognized complication of acute COVID-19 infection. As the COVID-19 pandemic moves into its third year, the prevalence of Long COVID continues to increase. Many individuals report symptoms lasting longer than a year, and a subset of this group is unable to work. This article will provide an update on Long COVID, with a particular focus on distinguishing it from other clinical entities. It will review several proposed disease mechanisms and will attempt to anticipate the impact on disability insurance.

Source: Timothy Meagher; Long COVID – One Year On. J Insur Med 2022; doi: https://doi.org/10.17849/insm-49-3-1-6.1 (Full text available as PDF file)

Serum NGF and BDNF in Long-COVID-19 Adolescents: A Pilot Study

Abstract:

COVID-19 (COronaVIrus Disease 19) is an infectious disease also known as an acute respiratory syndrome caused by the SARS-CoV-2. Although in children and adolescents SARS-CoV-2 infection produces mostly mild or moderate symptoms, in a certain percentage of recovered young people a condition of malaise, defined as long-COVID-19, remains. To date, the risk factors for the development of long-COVID-19 are not completely elucidated. Neurotrophins such as NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) are known to regulate not only neuronal growth, survival and plasticity, but also to influence cardiovascular, immune, and endocrine systems in physiological and/or pathological conditions; to date only a few papers have discussed their potential role in COVID-19.

In the present pilot study, we aimed to identify NGF and BDNF changes in the serum of a small cohort of male and female adolescents that contracted the infection during the second wave of the pandemic (between September and October 2020), notably in the absence of available vaccines. Blood withdrawal was carried out when the recruited adolescents tested negative for the SARS-CoV-2 (“post-infected COVID-19”), 30 to 35 days after the last molecular test. According to their COVID-19 related outcomes, the recruited individuals were divided into three groups: asymptomatics, acute symptomatics and symptomatics that over time developed long-COVID-19 symptoms (“future long-COVID-19”). As a control group, we analyzed the serum of age-matched healthy controls that did not contract the infection. Inflammatory biomarkers (TNF-α, TGF-β), MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were also analyzed with the free oxygen radicals’ presence as an oxidative stress index.

We showed that NGF serum content was lower in post-infected-COVID-19 individuals when compared to healthy controls; BDNF levels were found to be higher compared to healthy individuals only in post-infected-COVID-19 symptomatic and future long-COVID-19 girls, leaving the BDNF levels unchanged in asymptomatic individuals if compared to controls. Oxidative stress and inflammatory biomarkers were unchanged in male and female adolescents, except for TGF-β that, similarly to BDNF, was higher in post-infected-COVID-19 symptomatic and future long-COVID-19 girls. We predicted that NGF and/or BDNF could be used as early biomarkers of COVID-19 morbidity in adolescents.

Source: Petrella C, Nenna R, Petrarca L, Tarani F, Paparella R, Mancino E, Di Mattia G, Conti MG, Matera L, Bonci E, Ceci FM, Ferraguti G, Gabanella F, Barbato C, Di Certo MG, Cavalcanti L, Minni A, Midulla F, Tarani L, Fiore M. Serum NGF and BDNF in Long-COVID-19 Adolescents: A Pilot Study. Diagnostics (Basel). 2022 May 7;12(5):1162. doi: 10.3390/diagnostics12051162. PMID: 35626317. https://www.mdpi.com/2075-4418/12/5/1162/htm (Full text)

Neuropsychological measures of “Long COVID-19 Fog” in older subjects

Abstract:

Covid-19 is known to impact older people more severely and to cause a number of persistent symptoms during the recovery phase, including cognitive and neurological ones. We investigated the cognitive and neurological features of 100 elderly patients with confirmed diagnosis of Covid-19 evaluated in the post-acute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and other 8 neuropsychological tests. Overall, a total of 33 subjects were found to perform at a level considered to be pathological; more specifically, 33%, 23% and 20% failed on Trial Making, Digit Span Backwards and Frontal Evaluation Battery tests respectively.

Source: Alessandra Lauria, Angelo Carfì, Francesca Benvenuto, Giulia Bramato, Francesca Ciciarello, Sara Rocchi, Elisabetta Rota, Andrea Salerno, Leonardo Stella, Marcello Tritto, Antonella Di Paola, Cristina Pais, Matteo Tosato, Delfina Janiri, Gabriele Sani, Francesco Cosimo Pagano, Massimo Fantoni, Roberto Bernabei, Francesco Landi, Alessandra Bizzarro. Neuropsychological measures of “Long COVID-19 Fog” in older subjects. Clinics in Geriatric Medicine, 2022. ISSN 0749-0690, https://doi.org/10.1016/j.cger.2022.05.003. (Full text available as PDF file)

Exploring invisibility and epistemic injustice in Long Covid-A citizen science qualitative analysis of patient stories from an online Covid community

Abstract:

Background: In 2020, the long-lasting effects of the Covid-19 virus were not included in public messages of risks to public health. Long Covid emerged as a novel and enigmatic illness with a serious and life-changing impact. Long Covid is poorly explained by objective medical tests, leading to widespread disbelief and stigma associated with the condition. The aim of this organic research is to explore the physical and epistemic challenges of living with Long Covid.

Methods: Unlike any previous pandemic in history, online Covid communities and ‘citizen science’ have played a leading role in advancing our understanding of Long Covid. As patient-led research of this grassroots Covid community, a team approach to thematic analysis was undertaken of 66 patient stories submitted online to covid19-recovery.org at the beginning of the Covid-19 pandemic between April and September 2020.

Results: The overriding theme of the analysis highlights the complexities and challenges of living with Long Covid. Our distinct themes were identified: the life-changing impact of the condition, the importance of validation and how, for many, seeking alternatives was felt to be their only option.

Conclusions: Long Covid does not easily fit into the dominant evidence-based practice and the biomedical model of health, which rely on objective indicators of the disease process. Patient testimonies are vital to understanding and treating Long Covid, yet patients are frequently disbelieved, and their testimonies are not taken seriously leading to stigma and epistemic injustice, which introduces a lack of trust into the therapeutic relationship.

Patient contribution: The research was undertaken in partnership with our consumer representative(s) and all findings and subsequent recommendations have been coproduced.

Source: Ireson J, Taylor A, Richardson E, Greenfield B, Jones G. Exploring invisibility and epistemic injustice in Long Covid-A citizen science qualitative analysis of patient stories from an online Covid community. Health Expect. 2022 May 12. doi: 10.1111/hex.13518. Epub ahead of print. PMID: 35557480. https://onlinelibrary.wiley.com/doi/10.1111/hex.13518 (Full text)

A call to action to enhance understanding of long COVID in long-term care home residents

Letter to the editor:

The COVID-19 pandemic has highlighted significant vulnerabilities in the long-term care (LTC) sector, with widespread outbreaks and high rates of mortality in LTC homes (including nursing homes and assisted living facilities). In Canada, where our team is based, 81% of all COVID-19 deaths in the first wave of the pandemic were among LTC residents.1 By the end of 2020, there had been ~44,000 COVID-19 cases and 9200 related deaths among residents in Canadian LTC homes.2 Although most LTC residents survived acute COVID-19 infection, this does not mean they escaped the lasting impacts of long COVID. There are few studies investigating COVID-19 survivorship, including long COVID prevalence, management, and outcomes among LTC residents.

There has been increasing recognition and research on post-acute sequelae of COVID-19 (PASC), commonly known as long COVID. PASC is a complex and poorly defined syndrome with several possible mechanisms (e.g., viral persistence, immune dysregulation, autoimmunity).3 It involves diverse, persistent, and sometimes disabling symptoms lasting for weeks to months following acute COVID-19 infection (e.g., fatigue, shortness of breath, malaise, cough, pain, brain fog).4

Long COVID research is challenged by several factors. First, there is a lack of a globally standardized clinical case definition for long COVID. Some definitions,4 but not all, recognize several phases of long COVID, such as ongoing symptomatic COVID-19 (4 to 12 weeks) and post COVID-19 syndrome (≥12 weeks).5 Variations across definitions can inadvertently exclude groups with possible atypical presentation and different clusters of symptoms, such as in older adult and pediatric populations. Second, there lacks consensus on the onset and duration of long COVID symptoms and phases, as well as on the symptoms associated with long COVID. In fact, some studies identify more than 200 different symptoms.6 This hampers health professionals’ ability to diagnose and treat persons experiencing long-term sequelae of COVID-19, which also hinders clinical research on long COVID in particular.

Another shortcoming of long COVID research has been the exclusion of older adults – especially the oldest old (80+ years), those with multiple complex comorbidities, frailty, disability, dementia, and impaired immune function, which are characteristic of LTC residents. Challenges in studying this population include distinguishing between long COVID as a clinical entity separate from anticipated decline when recovering from acute illness, and intersecting mechanisms of advanced aging, pre-existing conditions, and long COVID. One of the few studies7 in older adults found that COVID-19 survivors (65+ years) had a higher risk of new or persistent clinical sequelae compared to non-infected older adults. Furthermore, older adult COVID-19 survivors only had increased risk differences of select sequelae (i.e., respiratory failure, dementia, and post-viral fatigue) compared to a group of older adults with viral lower respiratory tract illness.

Emerging, although limited, research in LTC residents has investigated symptoms, clinical outcomes, and wellbeing of COVID-19 survivors.8–10 However, these studies lack consideration of long COVID in their design and interpretation, such as the etiology, symptoms, and follow-up periods consistent with the current evidence on long COVID. The only study8 to our knowledge on COVID-19 disease trajectories in LTC residents found widespread, prolonged symptoms regardless of symptom severity, but neglected to assess differences in the acute COVID-19 infection versus long COVID phases. COVID-19 survivors in LTC have been found to have poorer outcomes related to malnutrition, weight loss, and frailty compared to non-infected residents.9, 10 Studies have also attributed physical and cognitive decline and depressive symptoms among COVID-19 survivors to the isolation and loneliness due to protective measures in LTC.9

Research design and interpretation of long COVID outcomes for LTC residents require special consideration of their complex comorbidities and diverse physical, psychological, and social care needs (e.g., communication impairments that limit self-reporting of symptoms, long COVID symptoms being attributed to pre-existing conditions).5 There is also a need to explore the impact and possible further exacerbation of policies and practices that were enacted in LTC homes during the pandemic. Given the waves of COVID-19 and its variants, it is also important to consider the impacts of policies and practices at different junctures in time, such as visitation restrictions and pre-vaccinations and boosters for LTC residents.

We make a call to action to the research community to rapidly address the dearth of research about long COVID among residents in LTC homes. The knowledge gaps and challenges outlined above emphasize the need for research to inform guidelines for long COVID management in this unique care context. This must be addressed in a timely fashion considering the ongoing COVID-19 outbreaks in LTC homes and the immense challenges currently faced by the LTC sector.

Source: Sorensen JM, Crooks VA, Freeman S, Carroll S, Davison KM, MacPhee M, Berndt A, Walls J, Mithani A. A call to action to enhance understanding of long COVID in long-term care home residents. J Am Geriatr Soc. 2022 May 14. doi: 10.1111/jgs.17889. Epub ahead of print. PMID: 35567575. https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.17889 (Full text)

Predictors of Post-Acute Sequelae of COVID-19 Development and Rehabilitation: A Retrospective Study

Abstract:

Objective: Clinical and demographic factors associated with the development, severity, and rehabilitation utilization of patients with Post-Acute Sequelae of COVID-19 (PASC) are not well defined. We examined the frequency of PASC, and the factors associated with rehabilitation utilization in a large adult population with PASC.

Design: Retrospective study SETTING: Hospital health system PARTICIPANTS: All COVID-19 patients from March 10, 2020 to January 17, 2021 INTERVENTION: Not applicable.

Main outcome measure: Descriptive analyses were conducted across the entire cohort along with an adult subgroup analysis. A logistic regression was performed to assess factors associated with PASC development and rehabilitation utilization.

Results: In an analysis of 19,792 patients, the frequency of PASC was 42.8% in the adult population. Patients with PASC compared to those without had a higher utilization of rehabilitation services (8.6% vs 3.8%, p<0.001). Risk factors for rehabilitation utilization in patients with PASC included younger age (OR 0.99, 95% CI 0.98-1.00; p=0.01). In addition to several comorbidities and demographics factors, risk factors for rehabilitation utilization solely in the inpatient population included male sex (OR 1.24, 95% CI 1.02-1.50; p=0.03) with patients on angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers three months prior to COVID-19 infections having a decreased risk of needing rehabilitation (OR 0.80, 95% CI 0.64-0.99; p=0.04).

Conclusion: Patients with PASC had higher rehabilitation utilization. We identified several clinical and demographic factors associated with the development of PASC and rehabilitation utilization.

Source: Abdelwahab N, Ingraham NE, Nguyen N, Siegel L, Silverman G, Sahoo HS, Pakhomov S, Morse LR, Billings J, Usher MG, Melnik TE, Tignanelli CJ, Ikramuddin F. Predictors of Post-Acute Sequelae of COVID-19 Development and Rehabilitation: A Retrospective Study. Arch Phys Med Rehabil. 2022 May 12:S0003-9993(22)00397-5. doi: 10.1016/j.apmr.2022.04.009. Epub ahead of print. PMID: 35569640; PMCID: PMC9098397. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098397/ (Full text)

Respiratory muscle dysfunction in long-COVID patients

Abstract:

Purpose: Symptoms often persistent for more than 4 weeks after COVID-19-now commonly referred to as ‘Long COVID’. Independent of initial disease severity or pathological pulmonary functions tests, fatigue, exertional intolerance and dyspnea are among the most common COVID-19 sequelae. We hypothesized that respiratory muscle dysfunction might be prevalent in persistently symptomatic patients after COVID-19 with self-reported exercise intolerance.

Methods: In a small cross-sectional pilot study (n = 67) of mild-to-moderate (nonhospitalized) and moderate-to-critical convalescent (formerly hospitalized) patients presenting to our outpatient clinic approx. 5 months after acute infection, we measured neuroventilatory activity P0.1, inspiratory muscle strength (PImax) and total respiratory muscle strain (P0.1/PImax) in addition to standard pulmonary functions tests, capillary blood gas analysis, 6 min walking tests and functional questionnaires.

Results: Pathological P0.1/PImax was found in 88% of symptomatic patients. Mean PImax was reduced in hospitalized patients, but reduced PImax was also found in 65% of nonhospitalized patients. Mean P0.1 was pathologically increased in both groups. Increased P0.1 was associated with exercise-induced deoxygenation, impaired exercise tolerance, decreased activity and productivity and worse Post-COVID-19 functional status scale. Pathological changes in P0.1, PImax or P0.1/PImax were not associated with pre-existing conditions.

Conclusions: Our findings point towards respiratory muscle dysfunction as a novel aspect of COVID-19 sequelae. Thus, we strongly advocate for systematic respiratory muscle testing during the diagnostic workup of persistently symptomatic, convalescent COVID-19 patients.

Source: Hennigs JK, Huwe M, Hennigs A, Oqueka T, Simon M, Harbaum L, Körbelin J, Schmiedel S, Schulze Zur Wiesch J, Addo MM, Kluge S, Klose H. Respiratory muscle dysfunction in long-COVID patients. Infection. 2022 May 16:1–7. doi: 10.1007/s15010-022-01840-9. Epub ahead of print. PMID: 35570238; PMCID: PMC9108020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108020/ (Full text)

A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS

Dear Editors,

As case numbers of coronavirus disease 19 (COVID-19) increase, chronic symptoms, including those of autonomic dysfunction, are being reported with increasing frequency [], leading to the diagnosis of post-acute sequelae of COVID-19 (PASC), or Long-COVID. In addition, small fiber neuropathy (SFN) has been reported after viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) []. These associations have prompted our group to systematically perform autonomic testing and skin biopsies in a cohort of patients who have developed postural tachycardia syndrome (POTS) as a consequence of PASC (Long-COVID POTS). As part of this evaluation, all skin biopsy samples undergo immunohistochemical analysis of both intraepidermal nerve fiber density (IENFD) and phosphorylated α-synuclein (p-syn) [], the pathological form of α-synuclein associated with the neurodegenerative diseases of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF), as well as isolated REM sleep behavior disorder (iRBD), a prodromal manifestation of synucleinopathy for the majority of patients.

Read the rest of this article HERE. 

Source: Miglis MG, Seliger J, Shaik R, Gibbons CH. A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS. Clin Auton Res. 2022 May 16:1–4. doi: 10.1007/s10286-022-00867-0. Epub ahead of print. PMID: 35570247; PMCID: PMC9108014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108014/ (Full text)

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID

Abstract:

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods.
Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID “brain fog”, while this probability further enlarged if the Nrf2 A allele was also present.
The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.
Source: Ercegovac M, Asanin M, Savic-Radojevic A, Ranin J, Matic M, Djukic T, Coric V, Jerotic D, Todorovic N, Milosevic I, Stevanovic G, Simic T, Bukumiric Z, Pljesa-Ercegovac M. Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID. Antioxidants. 2022; 11(5):954. https://doi.org/10.3390/antiox11050954  https://www.mdpi.com/2076-3921/11/5/954/htm (Full text)