Tag: covid-19

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)

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)

Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome

Abstract:

Background: Long COVID (coronavirus disease 2019) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor κ B (NF-κB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production.

Objective: The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition.

Methods: Extensive research was conducted in medical literature data bases by applying terms such as “long COVID” associated with “persistence of the SARS-CoV-2 virus” “spike protein’ “COVID-19” and “biologic therapies.”

Results and Conclusions: In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome.

Source: Buonsenso D, Piazza M, Boner AL, Bellanti JA. Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome. Allergy Asthma Proc. 2022 May 1;43(3):187-193. doi: 10.2500/aap.2022.43.220018. PMID: 35524358. https://pubmed.ncbi.nlm.nih.gov/35524358/ https://www.ingentaconnect.com/content/ocean/aap/2022/00000043/00000003/art00003;jsessionid=pp9ea7gev7kv.x-ic-live-01#  (Full text available as download)

Long COVID: aiming for a consensus

The spectrum of signs and symptoms that can newly occur and persist for months to years after SARS-CoV-2 infection was initially named long COVID. This term was collectively created by the patient community in the spring of 2020, and was later followed by other terms, such as post-COVID-19 condition, post-acute sequelae of SARS-CoV-2 infection, and post-COVID syndrome. This condition can affect different organs and body systems, with a wide range of signs and symptoms reported. Given the magnitude of the sequelae of SARS-CoV-2 infection, it is essential to agree upon the nomenclature and definition to assess its incidence, subtypes, and severity. This process cannot be left to agencies, health-care providers, or researchers alone, but requires extensive consultation, notably including the people affected.

In early 2021, WHO established technical working groups to provide a clinical case definition for this condition and amplified the calls of patient groups for recognition, research, and rehabilitation. A rapidly increasing number of studies started to investigate the incidence and prevalence, features, and risk factors of the prolonged sequelae of SARS-CoV-2 infection, the underlying mechanisms, and case management approaches.

There are concerns about differences in terminology, with some public health experts and policy makers avoiding the term long COVID. The use of different terms can raise worries, especially among those with lived experience of the condition who originally coined the term long COVID. Many issues have been raised by patient-researchers and other adopters of the term. One issue is epistemic injustice in medicine, including the poor recognition of patient-led expertise. Patient perspectives emphasise the tradition in medical history that those who first identify and describe a condition, name it. In the case of long COVID, it was people with lived experience of it who brought it to the world’s attention and described it via a wide range of methods. The first publication on prolonged symptoms of COVID-19 was authored by patient-researchers with long COVID, later known as the Patient-Led Research Collaborative. Another issue is that the severity, features, and urgency of long COVID—as highlighted by patients—are not fully addressed within the framework of other terms and definitions. Long COVID remains the patient-preferred term.

Read the rest of this article HERE.

Source: Munblit D, O’Hara ME, Akrami A, Perego E, Olliaro P, Needham DM. Long COVID: aiming for a consensus [published online ahead of print, 2022 May 4]. Lancet Respir Med. 2022;S2213-2600(22)00135-7. doi:10.1016/S2213-2600(22)00135-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067938/ (Full text)

Caring for the carers: understanding long covid in our diverse healthcare workforce

In the United Kingdom (UK), there have been over 21.4 million confirmed cases of covid-19 as of April 2022.1 Evidence has emerged that some patients are experiencing long term symptoms and complications that extend beyond the acute infection phase, which is now widely known as long covid.23 According to the most recent UK Government’s Office for National Statistics data (April 2021), approximately 1.7 million individuals in the UK reported experiencing covid-19 symptoms for longer than four weeks.4 Of these, 690% had covid-19 for the first time at least 12 weeks previously, and 45% had covid-19 at least a year ago.4

As the covid-19 pandemic has progressed, there has been increasing evidence that healthcare workers, especially those from ethnic minority backgrounds, may be at particularly high risk of poor physical and mental health outcomes.5 This is likely to be attributed to the many challenges that healthcare workers face while working in these circumstances, including the high work demand, shortage of staff, lack of personal protective equipment (PPE), rapid changes in protocols and guidance, and long working hours, as well as their increased risk of covid-19 infection and severe disease.56 As a result, healthcare workers may also be more likely than the general population to be affected by long covid, with a disproportionate burden among ethnic minorities.

Read the rest of this article HERE.

Source: Amani Al-Oraibi, Katherine Woolf, Laura B Nellums, Carolyn Tarrant, Habib Naqvi, Manish Pareek. Caring for the carers: understanding long covid in our diverse healthcare workforce. BMJ 2022;377:o1152 https://www.bmj.com/content/377/bmj.o1152.full (Full text)