Tag: covid-19

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.

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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)

Autonomic dysfunction in long-COVID syndrome: a neurophysiological and neurosonology study

Dear Sirs,

A significant proportion of patients infected from SARS-CoV-2 experience new, recurring, or ongoing symptoms usually 3 months after infection that may last for weeks or months and comprise the so-called Long-COVID Syndrome (LCS). Most frequent neurological symptoms include fatigue, memory/attention deficits, sleep disorders, myalgias and hyposmia []. The occurrence of LCS is not associated with the severity of foregoing acute COVID-19 nor have specific predisposing factors been identified so far. LCS shares common features with two other diseases, Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS): young women are predominantly affected, the etiology is unknown, although a previous viral infection is suspected, and both conditions have symptoms similar to those of LCS. Autonomic Nervous System (ANS) maladaptation has been proposed as a possible pathogenetic underlying mechanism. [, ]

Hence, a case–control study was conducted to investigate if ANS dysfunction may contribute to LCS. Consecutive, adult patients, with history of laboratory-confirmed COVID-19 without hospitalization, presenting with persistent LCS symptoms for > 3 months from COVID-19 onset, including fatigue, cognitive impairment (brain fog), orthostatic dizziness, palpitations, breathlessness or gastrointestinal symptoms, were evaluated at a referral center in Athens, Greece (“Attikon” University Hospital) between September 2021 and December 2021. LCS patients with cardiovascular complications or diabetes were excluded. Controls included colleagues, nursing staff and volunteers without history of SARS-COV-2 infection, cardiovascular diseases, diabetes and ANS disorders. Evaluation of ANS function was performed by Sympathetic Skin Response (SSR) to investigate the Sympathetic Nervous System (SNS), and the cross-sectional area (CSA) of the Vagus Nerve (VN) was assessed by ultrasound to investigate the Parasympathetic Nervous System (PNS) []. A detailed description of the methods is available in the online-only supplement. The study was approved by the Institutional Research Bioethics. Informed consent was obtained by all participants. Statistical analysis was performed using the Statistical Package for Social Science (SPSS Inc., version 24.0 for Windows; IBM, Armonk, NY, USA). Descriptive statistics are given as the mean and standard deviation, frequency, and percentage. Statistical comparisons between different groups were performed using the chi-square test (or exact test) for binary outcomes, and Student’s t test or Mann–Whitney U test for continuous variables as appropriate.

Read the full article HERE.

Source: Papadopoulou M, Bakola E, Papapostolou A, Stefanou MI, Gaga M, Zouvelou V, Michopoulos I, Tsivgoulis G. Autonomic dysfunction in long-COVID syndrome: a neurophysiological and neurosonology study. J Neurol. 2022 May 10:1–2. doi: 10.1007/s00415-022-11172-1. Epub ahead of print. PMID: 35536408; PMCID: PMC9086662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086662/ (Full text)

Exploring trajectory recovery curves of post-COVID cognitive symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study

Dear Sirs,

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, responsible of causing coronavirus disease 2019 (COVID-19), primary affects the respiratory system; however, neurological symptoms (e.g., ageusia, anosmia, headache) and also other severe complication are commonly experienced at the acute phase [, ]. Neurological symptoms presented at the acute COVID-19 phase such as headache [] or anosmia [] are likely present at a post-COVID phase; however, other neurological symptoms, e.g., cognitive disorders, are “de novo” developed in up to 22% of COVID-19 survivors []. A recent meta-analysis reported prevalence rates of 32%, 27% and 22% for post-COVID brain fog, memory loss, and attention/concentration problems the six months after respectively []. However, the presence of post-COVID cognitive symptoms are questioned by others [].

Interestingly, the recent definition of post-COVID includes cognitive dysfunction as one of the most common symptoms, after fatigue or dyspnoea []. The presence of post-COVID symptoms is overall associated with worse quality of life []. In fact, the presence of post-COVID cognitive symptoms represents a challenge for affected individuals since these symptoms affect daily life []. Although the presence of post-COVID cognitive symptoms is associated with nervous system changes [], it seems that these symptoms generally improve over time []. However, most studies investigating these symptoms have used cross-sectional designs. Therefore, understanding the longitudinal pattern of post-COVID cognitive symptoms may have significant implications in diagnosis, triaging, and management of post-COVID individuals.

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Source: Fernández-de-Las-Peñas C, Martín-Guerrero JD, Cancela-Cilleruelo I, Rodríguez-Jiménez J, Moro-López-Menchero P, Pellicer-Valero OJ. Exploring trajectory recovery curves of post-COVID cognitive symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study. J Neurol. 2022 May 10:1–5. doi: 10.1007/s00415-022-11176-x. Epub ahead of print. PMID: 35538169; PMCID: PMC9090121. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090121/ (Full text)