Tag: long Covid

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

Abstract:

Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation of the pathobiological matrix is lacking. Several potential disease mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial and muscular disturbances, cardiovascular anomalies, and dysfunction of the peripheral and central nervous systems. Yet, it remains unclear whether and how these pathways may be related and orchestrated.

Here we explore the hypothesis that a common denominator of the pathobiological processes in ME/CFS may be central nervous system dysfunction due to impaired or pathologically reactive neuroglia (astrocytes, microglia and oligodendrocytes). We will test this hypothesis by reviewing, in reference to the current literature, the two most salient and widely accepted features of ME/CFS, and by investigating how these might be linked to dysfunctional neuroglia.

From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features – post exertional malaise and decreased cerebral blood flow – are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.

Source: Renz-Polster H, Tremblay ME, Bienzle D, Fischer JE. The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure. Front Cell Neurosci. 2022 May 9;16:888232. doi: 10.3389/fncel.2022.888232. PMID: 35614970; PMCID: PMC9124899. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124899/ (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)

Unexplained post-acute infection syndromes

Abstract:

SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine.

The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis.

In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.

Source: Choutka J, Jansari V, Hornig M, Iwasaki A. Unexplained post-acute infection syndromes. Nat Med. 2022 May;28(5):911-923. doi: 10.1038/s41591-022-01810-6. Epub 2022 May 18. PMID: 35585196. https://www.nature.com/articles/s41591-022-01810-6 (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.

Read the rest of this article HERE.

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)

Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

Abstract:

Background: Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.

Methods: A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.

Results: Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47-169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1-3 months and p 0.01 at 6-9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1-3 months follow up, but not at 6-9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments.

Conclusion: Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.

Source: Buonsenso D, Munblit D, Pazukhina E, Ricchiuto A, Sinatti D, Zona M, De Matteis A, D’Ilario F, Gentili C, Lanni R, Rongai T, Del Balzo P, Fonte MT, Valente M, Zampino G, De Rose C, Sigfrid L, Valentini P; FIMP-Roma. Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol. Front Pediatr. 2022 Apr 21;10:834875. doi: 10.3389/fped.2022.834875. PMID: 35529336; PMCID: PMC9070551.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070551/ (Full text)

Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study

Abstract:

Background: The long-COVID syndrome (LCS), defined by residual symptoms from acute COVID-19 for <60 days, affects about one-third of all COVID survivors and is an emerging public health challenge. Empirical data about the range of symptoms or the utility of acupuncture alone for the LCS are very limited.

Case: This observational case study of a 46-year-old male with LCS was conducted to preliminarily define the range of symptoms, a Traditional Chinese Medicine (TCM) diagnostic structure, and evaluate the potential utility of prescribed acupuncture for LCS.

Results: The primary TCM diagnostic patterns from this patient’s LCS presentation included Lung Qi and Yin Deficiency, Qi and Blood Stagnation, and Spleen Qi Deficiency with dampness. Acupuncture for this patient was associated with reduced symptoms and signs of LCS.

Conclusion: A preliminary TCM diagnostic structure for LCS was defined. Acupuncture appears to have been helpful for a patient with LCS. Further research is needed to demonstrate the efficacy of acupuncture and/or other TCM modalities for LCS.

Source: Michael Hollifield, Karen Cocozza, Teresa Calloway, Jennifer Lai, Brianna Caicedo, Kala Carrick, Ruth Alpert, and An-Fu Hsiao. Medical Acupuncture (ahead of print). http://doi.org/10.1089/acu.2021.0088 https://www.liebertpub.com/doi/full/10.1089/acu.2021.0088  (Full text)