Category: Overlapping Illnesses

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)

An Unexpected Journey: The Lived Experiences of Patients with Long-Term Cognitive Sequelae After Recovering from COVID-19

Abstract:

This current study explored the lived experiences of patients with long-term cognitive sequelae after recovering from COVID-19. A qualitative design with in-depth interviews and an analysis inspired by Ricoeur’s interpretation theory was utilised. Contracting COVID-19 and suffering long-term sequelae presented as a life-altering event with significant consequences for one’s social, psychological and vocational being in the world in the months following the infection.

Patients living with long-term cognitive sequelae after COVID-19 were in an unknown life situation characterised by feelings of anxiety, uncertainty and concerns about the future, significantly disrupting their life trajectory and forcing them to change their ways of life. While awaiting studies on treatment, symptom management and recovery after persistent sequelae of COVID-19, clinicians and researchers may find inspiration in experiences of other health conditions with similar phenomenology, such as ME/chronic fatigue syndrome and chronic headaches.

Source: Loft MI, Foged EM, Koreska M. An Unexpected Journey: The Lived Experiences of Patients with Long-Term Cognitive Sequelae After Recovering from COVID-19. Qual Health Res. 2022 May 21:10497323221099467. doi: 10.1177/10497323221099467. Epub ahead of print. PMID: 35603563. https://pubmed.ncbi.nlm.nih.gov/35603563/

Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis

Abstract:

Post-COVID syndrome (PCS) or Long-COVID is an increasingly recognised complication of acute SARS-CoV-2 infection, characterised by persistent fatigue, reduced exercise tolerance chest pain, shortness of breath and cognitive slowing. Acute COVID-19 is strongly linked with increased risk of thrombosis; a prothrombotic state, quantified by elevated Von Willebrand Factor (VWF) Antigen (Ag):ADAMTS13 ratio, and is associated with severity of acute COVID-19 infection. We investigated if patients with PCS also had evidence of a pro-thrombotic state associating with symptom severity.

In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk including VWF(Ag):ADAMTS13 ratio, was investigated. An elevated VWF(Ag):ADAMTS13 ratio (≥1.5) was raised in nearly one-third of the cohort and four times more likely in patients with impaired exercise capacity as evidenced by desaturation ≥3% and/or rise in lactate level more than 1 from baseline on 1-minute sit to stand test and/or 6-minute walk test (p<0.0001). 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag):ADAMTS13 ratio ≥1.5 (p<0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in some patients with PCS.

These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and highlight a potential role for antithrombotic therapy in the management of these patients.

Source: Prasannan N, Heightman M, Hillman T, Wall E, Bell R, Kessler A, Neave L, Doyle AJ, Devaraj A, Singh D, Dehbi HM, Scully M. Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis. Blood Adv. 2022 May 11:bloodadvances.2021006944. doi: 10.1182/bloodadvances.2021006944. Epub ahead of print. PMID: 35543533; PMCID: PMC9098525. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098525/ (Full text)

Hyperbaric Oxygen for Treatment of Long COVID Syndrome (HOT-LoCO); Protocol for a Randomised, Placebo-Controlled, Double-Blind, Phase II Clinical Trial

Abstract:

Introduction: Long COVID, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, post-exertional malaise, and cognitive dysfunction. There is currently no effective treatment, and the underlying mechanisms are unknown although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in Long COVID. This randomised placebo-controlled clinical trial will explore HBOT as a potential treatment for Long COVID.

The primary objective is to evaluate if HBOT improves health related quality of life (HRQoL) for patients with Long COVID compared to placebo/sham. The main secondary objectives are to evaluate whether HBOT improves endothelial function, objective physical performance, and short term HRQoL.

Methods and Analysis: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to Long COVID, with low HRQoL. Clinical data, HRQoL-questionnaires, blood samples, objective tests and activity meter data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over six weeks. Assessments for safety and efficacy will be performed at six, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND-36) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent Data Safety Monitoring Board.

Ethics and Dissemination: The trial is approved by The Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative, and inconclusive results will be published in peer-reviewed scientific journals with open access.

Trial Registration NCT04842448. EudraCT: 2021-000764-30 Strengths and limitations of this trial Strengths -Randomised placebo-controlled, double-blind, parallel groups, clinical trial in compliance with ICH-GCP -Evaluation of safety and efficacy, including objective and explanatory endpoints -Independent Data Safety Monitoring Board (DSMB) Limitations -New syndrome with unknown mechanisms -Power calculation is based on similar syndromes -Selection bias as patients are enrolled from the same post-COVID clinic

Source: Anders Kjellberg, Lina Abdel-Halim, Adrian Hassler, Sara El Gharbi, Sarah Al-Ezerjawi, Emil Boström, Carl Johan Sundberg, John Pernow, Koshiar Medson, Jan Kowalski, Kenny A Rodriguez-Wallberg, Xiaowei Zheng, Sergiu Bogdan Catrina, Michael Runold, Marcus Ståhlberg, Judith Bruchfeld, Malin Nygren-Bonnier, Peter Lindholm. Hyperbaric Oxygen for Treatment of Long COVID Syndrome (HOT-LoCO); Protocol for a Randomised, Placebo-Controlled, Double-Blind, Phase II Clinical Trial. medRxiv 2022.05.20.22275312; doi: https://doi.org/10.1101/2022.05.20.22275312 https://www.medrxiv.org/content/10.1101/2022.05.20.22275312v1

Neurological and Psychiatric Symptoms of COVID-19: A Narrative Review

Abstract:

Recently dubbed Long COVID or Long-Haul COVID, those recovering from the initial COVID-19 infection may maintain clinical signs for longer than two or more weeks following the initial onset of the infection. The virus can gain entry into the CNS through axonal transport mediated through the olfactory nerve or hematogenous spread and can also cross the blood–brain barrier to access the temporal lobe and the brainstem. The neurologic and neuropsychiatric symptoms associated with COVID-19 patients are becoming a highly studied area due to the increased frequency of reported cases.
Multiple hospital case series and observational studies have found a headache to be a common symptom among patients who are symptomatic with the SARS-CoV-2 virus. The headache described by many of these patients is similar to new daily persistent headache (NDPH). NDPH potentially develops in response to pro-inflammatory cytokines during a persistent systemic or CNS inflammation, mostly due to the initial infection. The treatments investigated were high-dose steroids, tetracycline derivatives, onabotulinum toxin type A, and long-term multidrug regimens. Among the identified symptoms of post-COVID-19 viral illness, fatigue appears to be the most ubiquitous. High-dose vitamin C is currently a suggested therapy proposed for its antioxidant, anti-inflammatory, and immunomodulatory properties.
The mental health consequences of this diagnosis are being identified among large portions of COVID-19 survivors. Among these consequences, cases of major depressive disorder (MDD) and anxiety are being reported and closely examined. The aim of this narrative review is to highlight the neurological and psychiatric symptoms that have been associated with Long-Haul COVID and their possible treatments.
Source: Edinoff AN, Chappidi M, Alpaugh ES, Turbeville BC, Falgoust EP, Cornett EM, Murnane KS, Kaye AM, Kaye AD. Neurological and Psychiatric Symptoms of COVID-19: A Narrative Review. Psychiatry International. 2022; 3(2):158-168. https://doi.org/10.3390/psychiatryint3020013 https://www.mdpi.com/2673-5318/3/2/13/htm (Full text)

Intimate partner violence and women living with episodic disabilities: a scoping review protocol

Abstract:

Background: Violence towards women with disabilities is most commonly perpetrated by current or former intimate partners and more than half of disabled women experience intimate partner violence in their lifetime. Disabilities differ by presence, type, and complexity, yet are commonly researched collectively. A more nuanced understanding of the relationship between intimate partner violence and episodic disability is required to better support women living with these concurrent challenges. The objective of this scoping review is to investigate and synthesize the literature reporting on intimate partner violence for women living with an episodic disability to identify key concepts and knowledge gaps on this topic. Ultimately, this review aims to improve health services for this stigmatized group of women with episodic disabilities.

Methods: This scoping review will consider all studies that focus on women (18 years of age or older) who have experienced intimate partner violence and have an episodic disability. Episodic disabilities will include multiple sclerosis, chronic fatigue syndrome, fibromyalgia, lupus, or rheumatoid arthritis. The broad review question is what is known about intimate partner violence within the context of women living with an episodic disability? Databases to be searched include MEDLINE (OVID), CINAHL, Embase, PsychInfo, and Scopus with no limits on language or time frame. Joanna Briggs Institute methodology will guide this scoping review to address the review questions outlined in the protocol. For papers that meet the inclusion criteria, data will be extracted, and findings will be presented in tables and narrative form. A PRISMA table will be included to enhance the transparency of the process. A descriptive qualitative approach to analysis will be conducted following Braun and Clarke’s reflexive thematic analysis. The findings of the scoping review will be presented through a thematic narrative.

Discussion: Findings from this review will be used to identify important priorities for future research based on knowledge gaps and inform both health care practices and health and social interventions for women living with intimate partner violence and episodic disabilities.

Source: Campbell KA, Ford-Gilboe M, Stanley M, MacKinnon K. Intimate partner violence and women living with episodic disabilities: a scoping review protocol. Syst Rev. 2022 May 18;11(1):97. doi: 10.1186/s13643-022-01972-x. PMID: 35585642. https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-022-01972-x  (Full text)