Tag: 2023

A qualitative study to explore children’s experience of having long-Covid

There is currently uncertainty and limited research surrounding long-COVID in the paediatric population. Reports are conflicting regarding the prevalence, duration, and impact of long COVID on children. Despite the limited evidence, it is becoming increasingly apparent that numerous children are experiencing long-term physical and psychological effects of COVID19 many months after the initial infection. This thesis aimed to investigate the lived experience of children with long-COVID.
Part one of this portfolio presents a systematic review of the experiences of parents who provide care for a child with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The findings of the review indicate a paucity of research on parents’ experiences. However, it is apparent that caring for a child with ME/CFS is an all-encompassing, relentless undertaking, which can detrimentally impact parents’ well-being, everyday life, and relationships.
Given both ME/CFS and long-COVID are both post-viral illnesses, sharing similar symptoms, with low-level immune system activation. It may be conjectured that the existing knowledge on children with ME/CFS could benefit both children suffering from long-COVID and help inform parents on how best to care for their children.
Part two of this portfolio presents an empirical paper exploring the lived-experience of young people with long-COVID. Reflexive thematic analysis found three key themes, specifically, the perceived barriers to coping with long-COVID, ongoing associated emotional distress, and a desire for an integrated approach to long-COVID care.
Source: Carolyn Noorderhaven. A qualitative study to explore children’s experience of having long-Covid. Doctoral thesis: University of Surrey, School of Psychology. https://openresearch.surrey.ac.uk/esploro/outputs/doctoral/A-qualitative-study-to-explore-childrens/99813065702346?institution=44SUR_INST (Full text available as PDF file)

A National Evaluation of Outcomes in Long COVID Services using Digital PROM Data from the ELAROS Platform

Summary:

Key findings of this service evaluation study:
• Patient characteristics: A sample of 5,318 patients from 14 participating NHS LC sites were analysed. The sample had a female:male ratio of 2.1:1. The average age was 48.4 yrs, with 87% (of those whose ethnicity was recorded) of white ethnicity and 9% of Black or Asian ethnicity.
• Comorbidities: This sample of patients had a low prevalence of co-morbidities (7%) with a clear onset of new LC symptoms after their COVID-19 infection supporting the onset of a new condition in this cohort of previously healthy individuals.
• Duration of LC: The average duration of LC in this sample was 384 days (>12 months) at first assessment in an LC site, with symptoms still ongoing at presentation, with more than 90% of the sample being non-hospitalised patients.
• Digital platform: A total of 17,471 PROMs (C19-YRS and EQ-5D-5L) were completed by this sample of patients with at least 1,532 participants completing multiple assessments on the same PROM on the digital PROM platform. The completion of PROMs around the 3-month mark was low for both measures (11.7% for C19-YRS and 14.6% for EQ-5D-5L). The ones who completed PROMs both around the 3-month mark and the 6-month mark were 4.3% for C19-YRS and 5% for EQ-5D-5L. This limits the generalisability of the findings in this evaluation to all the LC population, but the findings remain valid for this cohort of individuals.
• New-onset disability: 3,395 patients who completed at least one C19-YRS questionnaire at first assessment showed significant new-onset symptom burden, functional disability, and deterioration of overall health since the COVID-19 infection.
• Comparison between LC and other chronic conditions: The cross-sectional EQ-5D-5L Index value of 3,438 patients suggests the burden and disability in LC are worse than that reported in the literature for Diabetes Mellitus, COPD, Heart Failure, and Multiple Sclerosis.
• 3-month follow-up: Among those who completed an initial C19-YRS assessment and another at 3 months, there was a statistically significant improvement in symptom burden, functional disability and overall health. Patients at 3 months however still had significant LC symptom
burden and disability compared to their pre-COVID-19 health status, i.e., their condition had improved, but they were far off from a complete recovery. Among those who completed EQ-5D- National Evaluation of Long COVID Service Outcomes using ELAROS Data (09 Oct 23) Page 3 of 31
5L, at first assessment and at 3 months, their EQ-5D-5L Index score did not show any statistically significant improvement, but the EQ-5D-5L VAS showed a statistically significant improvement.
• 6-month follow-up: Among those who completed measures at the first assessment, 3 months, and 6 months, C19-YRS and EQ-5D-5L VAS showed statistically significant improvement whereas EQ-5D-5L Index Value showed statistically significant deterioration. Patients at 6 months still had
significant LC symptom burden and disability compared to their pre-COVID-19 health status, i.e., their condition had improved but had not fully recovered. The follow-up changes in scores support the efficacy of interventions provided by LC services and suggest that continued specialist input is needed to manage these patients with persistent symptoms.
• C19-YRS (condition-specific measure) vs EQ-5D-5L (generic measure): The 3-month month follow-up changes in scores and responsiveness of PROMs highlight that C19-YRS is a more sensitive measure than EQ-5D-5L in this cohort of individuals with LC. This is in keeping with the literature recommending the use of condition-specific measures in addition to EQ-5D-5L.
• Vocational problems: 62% of this sample had their work role affected with them having to either be on sick leave, reduce hours, change roles, or quit roles. Only 21% were able to maintain their previous roles held prior to their COVID-19 infection. This is suggestive of considerable productivity loss and financial implications to the country.
• Fluctuating condition: In patients who completed multiple assessments, it was evident that LC is a fluctuant condition with no necessary linear trend of improvement or deterioration between the domains of symptom burden, functional disability, and overall health. This highlights the need to understand the triggers for the condition and invest in self-management and ongoing support from community healthcare services.
• Long-Term Condition: In most patients in this sample, LC has evidently become a Long-Term Condition (LTC) with fluctuations in their condition causing disability and significant deterioration of their overall health status seen even after 18 months of LC with no complete resolution or full recovery. There needs to be a national investment in managing this new LTC along with other LTCs.

Source: Dr Manoj Sivan, et al.  A National Evaluation of Outcomes in Long COVID Services using Digital PROM Data from the ELAROS Platform. National Evaluation of Long COVID Service Outcomes using ELAROS Data (09 Oct 23) https://locomotion.leeds.ac.uk/wp-content/uploads/sites/74/2023/10/National-Evaluation-of-LC-Service-Outcomes-using-ELAROS-Data-09-10-23.pdf (Full text)

A prospective randomized, double-blind placebo-controlled study to evaluate the effectiveness of neuroprotective therapy using functional brain MRI in patients with post-covid chronic fatigue syndrome

Abstract:

Background and purpose: to assess executive network using resting-state fMRI and patterns of brain activation using task fMRI with a cognitive paradigm, against the background of taking the drug in comparison with placebo in patients with post-COVID asthenic syndrome.

Methods: The study employed a prospective, randomized, double-blind, placebo-controlled trial approach to assess the efficacy of utilizing functional MRI of the brain as a neuroprotective therapy for treating patients with chronic fatigue syndrome following COVID-19. The study included 30 patients matched by sex and age with post-COVID asthenic syndrome. All patients were examined with MFI-20, MoCA, FAS-10 scales, MRI using a Siemens MAGNETOM Prisma 3 T scanner before and after a course of therapy with coordination complex with succinate acid anion (CCSA) or placebo (15 patients each) using resting state fMRI and with cognitive paradigm.

Results: The changes obtained as a result of the treatment of post-Covid asthenic syndrome demonstrated clinical superiority in the reduction of asthenic symptoms for the group of patients treated with CCSA (MFI-20 scores: -20·0 points in the CCSA group compared to -12 points in the placebo group, p = 0·043). The data obtained also correlate with the analysis of task fMRI and resting state fMRI may indicate an increase in the functional cognitive status after a course of therapy with CCSA. Clinically, this correlates with a statistically significant improvement in the MoCA score (2 points in the CCSA group compared to 1 point in the placebo group, p < 0·05).

Conclusions: The study demonstrates the potential effectiveness of CCSA therapy in relation to a wide range of symptoms (chronic fatigue syndrome/ asthenic syndrome and cognitive impairment) in patients with post-COVID syndrome. The first time demonstrated the effectiveness of neuroprotective therapy after post-COVID asthenic syndrome with the use of high-tech neuroimaging techniques.

Source: Tanashyan M, Morozova S, Raskurazhev A, Kuznetsova P. A prospective randomized, double-blind placebo-controlled study to evaluate the effectiveness of neuroprotective therapy using functional brain MRI in patients with post-covid chronic fatigue syndrome. Biomed Pharmacother. 2023 Oct 18;168:115723. doi: 10.1016/j.biopha.2023.115723. Epub ahead of print. PMID: 37862966. https://www.sciencedirect.com/science/article/pii/S0753332223015214 (Full study)

Cytometry profiling of ex vivo recall responses to Coxiella burnetii in previously naturally exposed individuals reveals long-term changes in both adaptive and innate immune cellular compartments

Abstract:

Introduction: Q fever, caused by the intracellular bacterium Coxiella burnetii, is considered an occupational and biodefense hazard and can result in debilitating long-term complications. While natural infection and vaccination induce humoral and cellular immune responses, the exact nature of cellular immune responses to C. burnetii is incompletely understood. The current study seeks to investigate more deeply the nature of long-term cellular recall responses in naturally exposed individuals by both cytokine release assessment and cytometry profiling.

Methods: Individuals exposed during the 2007-2010 Dutch Q fever outbreak were grouped in 2015, based on a C. burnetii-specific IFNγ release assay (IGRA), serological status, and self-reported clinical symptoms during initial infection, into asymptomatic IGRA-negative/seronegative controls, and three IGRA-positive groups (seronegative/asymptomatic; seropositive/asymptomatic and seropositive/symptomatic). Recall responses following in vitro re-stimulation with heat-inactivated C. burnetii in whole blood, were assessed in 2016/2017 by cytokine release assays (n=55) and flow cytometry (n=36), and in blood mononuclear cells by mass cytometry (n=36).

Results: Cytokine release analysis showed significantly elevated IL-2 responses in all seropositive individuals and elevated IL-1β responses in those recovered from symptomatic infection. Comparative flow cytometry analysis revealed significantly increased IFNγ, TNFα and IL-2 recall responses by CD4 T cells and higher IL-6 production by monocytes from symptomatic, IGRA-positive/seropositive individuals compared to controls. Mass cytometry profiling and unsupervised clustering analysis confirmed recall responses in seropositive individuals by two activated CD4 T cell subsets, one characterized by a strong Th1 cytokine profile (IFNγ+IL-2+TNFα+), and identified C. burnetii-specific activation of CD8 T cells in all IGRA-positive groups. Remarkably, increased C. burnetii-specific responses in IGRA-positive individuals were also observed in three innate cell subpopulations: one characterized by an IFNγ+IL-2+TNFα+ Th1 cytokine profile and lack of canonical marker expression, and two IL-1β-, IL-6- and IL-8-producing CD14+ monocyte subsets that could be the drivers of elevated secretion of innate cytokines in pre-exposed individuals.

Discussion: These data highlight that there are long-term increased responses to C. burnetii in both adaptive and innate cellular compartments, the latter being indicative of trained immunity. These findings warrant future studies into the protective role of these innate responses and may inform future Q fever vaccine design.

Source: Raju Paul S, Scholzen A, Reeves PM, Shepard R, Hess JM, Dzeng RK, Korek S, Garritsen A, Poznansky MC, Sluder AE. Cytometry profiling of ex vivo recall responses to Coxiella burnetii in previously naturally exposed individuals reveals long-term changes in both adaptive and innate immune cellular compartments. Front Immunol. 2023 Oct 11;14:1249581. doi: 10.3389/fimmu.2023.1249581. PMID: 37885896; PMCID: PMC10598782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598782/ (Full text)

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Abstract:

Background: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.

Methods: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections’ contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).

Results: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a “moderate association” by Cohen’s d test) compared to both healthy and diseased controls.

Conclusion: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Source: Hwang, JH., Lee, JS., Oh, HM. et al. Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis. J Transl Med 21, 763 (2023). https://doi.org/10.1186/s12967-023-04635-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04635-0 (Full text)

Long COVID-19 Symptoms Remedied by Anti-Viral Treatment in Neurosurgical Patients

Abstract:

The pandemic of COVID-19 is the largest in this century. Aside from the acute infection, some of the patients have been challenged with a complication that is known as long COVID-19. The symptoms of long COVID-19 are extensive and diverse. Long COVID-19 continues to plague many patients post-COVID-19 infection. No universal treatment has been found.

This study presents four patients who suffered from long COVID-19. Each patient presented with a different and diverse symptom of long COVID-19. Each of the patient’s symptoms resolved or greatly improved upon taking the anti-viral drug acyclovir. Acyclovir has been in use since 1981 and is generally considered safe. A novel theory as to the pathophysiology of long COVID-19 symptoms and the result of a new treatment is presented. The purpose of this study is to provide a foundation for much bigger studies and useful resources for further testing to halt long COVID-19.

Source: Beatty, R. M. (2023). Long COVID-19 Symptoms Remedied by Anti-Viral Treatment in Neurosurgical Patients. American Journal of Infectious Diseases, 19(3), 39-44. https://doi.org/10.3844/ajidsp.2023.39.44 https://thescipub.com/abstract/ajidsp.2023.39.44 (Full text available as PDF file)

Re: What happens inside a long covid clinic?

Dear Editor

As a patient with severe long covid and myalgic encephalomyelitis (M.E.), I was pleased to see the article ‘What happens in a long covid clinic?’ [1] raising awareness of the scale and impact of long covid and the importance of long covid clinics. According to a recent estimate by Altmann et al, 1 in 10 people who contract COVID-19 will be affected by long covid, whilst the oncoming impact of long covid on health systems, populations and economies will be “so large as to be unfathomable”.[2]

Around 2-14% of patients with long covid develop orthostatic tachycardia six to eight months after COVID infection and as many as 60% show some symptoms of POTS. [3] Yet there remain no agreed guidelines for POTS in long covid, making the early diagnosis and management of the condition in primary care challenging. NICE guidance on long covid only mentions POTS in passing with no information on management.[4] The approach outlined by Espinosa-Gonzalez and colleagues to diagnose and manage POTS in primary care could greatly improve function and health for people with POTS.[5]

While I commend the excellent NHS services highlighted in the feature [1], as a patient with severe long covid I would question how prevalent this integrated medically-led care model is across the country despite it being in the ‘The NHS plan for improving long covid services’.[6] Many patients I speak to in long covid support groups report long waits, only to then be offered basic wellbeing classes or rehabilitation without any active treatment for symptoms.

Access to clinics for the most severely affected is variable with not all services offering remote consultations or home visits. It is imperative that long covid clinics are medically led, inter-disciplinary and able to prescribe medications. Additionally, we need the same standard of care for patients with ME/CFS, who are still waiting for NICE guidance from 2021[7] to be implemented. A recent survey noted there remain significant gaps in provision for patients with ME/CFS.[8]

Previously young fit and healthy patients with severe long covid and ME are being left bed-bound without adequate diagnosis, support, care or treatment as there is no specialty or service that is set up to provide this. I went from climbing mountains and working on-call to unable to stand or feed myself in the space of 8 weeks with long covid – I am still severely affected a year later. Given the multi-system complexity of long covid and ME/CFS it is time for an interdisciplinary patient-centred service for post-viral illnesses that recognises the biological nature of the disease and the unique challenges patients with severe long covid and ME have with safely accessing services given their limited energy available, severe cognitive effects, physical immobility and range of complications across bodily systems.

The Department of Health and Social Care are currently seeking views on the interim delivery plan for ME/CFS care in an online consultation [9], which is relevant to both patient groups and professionals and could lay the groundwork for more comprehensive care of post-viral illnesses in the UK.

Yours sincerely,

Dr Alexis Gilbert BSc MBBS MPH FFPH

Source: MJ 2023;382:p1791 https://www.bmj.com/content/382/bmj.p1791/rr (Full text)

Long COVID: A Chronic Shortage of Blood. Pathophysiology and Treatment Proposal

Abstract:

My hypothesis is that the signs and symptoms of Long COVID can be explained by a shortage of blood in the body and a resulting deficient blood flow through nearly all organs. This shortage arises through damage to the blood-producing organs during the acute phase, while the breakdown of blood continues as normal, after an initial increase.

In order to ensure the perfusion of organs that are directly necessary for survival, the body takes the emergency measure of diverting blood from other organs and tissues. The perfusion of the blood-producing organs is also affected by this distribution measure, which hinders the smooth recovery of the total blood volume. The body is stuck in this vicious circle: a shortage of circulating blood hinders the recovery of blood production. This explains the long duration of Long COVID.

My proposed treatment of Long COVID focuses on the recovery of the correct volume of blood in the body of the right composition by the very careful administration of donor blood products under continuous expert supervision. A trial treatment can be performed in any hospital without much additional preparations, and has a lower associated risk for the patient than analysing the total blood. A diagnosis ex juvantibus, by therapeutic response, is therefore preferable, and will result in the healing process starting earlier.

Indications in blood laboratory values of a shortage of blood are a high serum ferritin due to internal breakdown of blood and values for haematocrit and albumin at reciprocal extremes of the reference ranges due to a stagnation of blood production.

Source: Molenaar, P.A. Long COVID: A Chronic Shortage of Blood. Pathophysiology and Treatment Proposal. Preprints 2023, 2023092109. https://doi.org/10.20944/preprints202309.2109.v1 https://www.preprints.org/manuscript/202309.2109/v1 (Full text available as PDF file)

Maximal Oxidative Capacity During Exercise is Associated with Muscle Power Output in Patients with Long coronavirus disease 2019 (COVID-19) Syndrome. A Moderation Analysis

Abstract:

Background & Aims: Long COVID syndrome (LCS) involves persistent symptoms experienced by many patients after recovering from coronavirus disease 2019 (COVID-19). We aimed to assess skeletal muscle energy metabolism, which is closely related to peak fat oxidation rates during exercise, in patients with LCS compared with healthy controls. We also examined whether muscle power output mediates the relationship between COVID-19 and skeletal muscle energy metabolism.

Methods: In this cross-sectional study, we enrolled 71 patients with LCS and 63 healthy controls. We assessed clinical characteristics such as body composition, physical activity, and muscle strength. We used cardiopulmonary exercise testing to evaluate substrate oxidation rates during graded exercise. We performed statistical analyses to compare group characteristics and peak fat oxidation differences based on power output.

Results: The two-way analysis of covariance (ANCOVA) results, adjusted for covariates, showed that the patients with LCS had lower absolute maximal fatty acid oxidation (MFO), relative MFO/fat-free mass (FFM), absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen uptake (VO2) at maximum fat oxidation (mL∙min−1) than the healthy controls (P < 0.05). Moderation analysis indicated that muscle power output significantly influenced the relationship between LCS and reduced peak fat oxidation (interaction β = −0.105 [95% confidence interval −0.174; −0.036]; P = 0.026). Therefore, when muscle power output was below 388 W, the effect of the LCS on MFO was significant (62% in our study sample P = 0.010). These findings suggest compromised mitochondrial bioenergetics and muscle function, represented by lower peak fat oxidation rates, in the patients with LCS compared with the healthy controls.

Conclusion: The patients with LCS had lower peak fat oxidation during exercise compared with the healthy controls, potentially indicating impairment in skeletal muscle function. The relationship between peak fat oxidation and LCS appears to be mediated predominantly by muscle power output. Additional research should continue investigating LCS pathogenesis and the functional role of mitochondria.

Source: Robinson Ramírez-Vélez, Sergio Oscoz-Ochandorena, Yesenia García-Alonso, Nora García-Alonso, Gaizka Legarra-Gorgoñon, Julio Oteiza, Ander Ernaga Lorea, Mikel Izquierdo, María Correa-Rodríguez. Maximal Oxidative Capacity During Exercise is Associated with Muscle Power Output in Patients with Long coronavirus disease 2019 (COVID-19) Syndrome. A Moderation Analysis. Clinical Nutrition ESPEN, 2023, ISSN 2405-4577, https://doi.org/10.1016/j.clnesp.2023.10.009. https://www.sciencedirect.com/science/article/pii/S2405457723021666 (Full text)

Brain fog in long COVID: A glutamatergic hypothesis with astrocyte dysfunction accounting for brain PET glucose hypometabolism

Abstract:

Brain [18F]FDG-PET scans have revealed a glucose hypometabolic pattern in patients with long COVID. This hypometabolism might reflect primary astrocyte dysfunction. Astrocytes play a key role in regulating energy metabolism to support neuronal and synaptic activity, especially activity involving glutamate as the main neurotransmitter.

Neuroinflammation is one of the purported mechanisms to explain brain damage caused by infection with SARS-CoV-2. Microglial activation can trigger reactive astrogliosis, contributing to neuroinflammatory changes. These changes can disturb glutamatergic homeostasis, ultimately leading to cognitive fatigue, which has been described in other clinical situations.

We hypothesize that glutamatergic dysregulation related to astrocyte dysfunction could be the substrate of brain PET hypometabolism in long COVID patients with brain fog. Based on these elements, we propose that therapeutics targeting astrocytic glutamate regulation could help mitigate long COVID neurological manifestations.

Source: Tatiana Horowitz, Luc Pellerin, Eduardo R. Zimmer, Eric Guedj. Brain fog in long COVID: A glutamatergic hypothesis with astrocyte dysfunction accounting for brain PET glucose hypometabolism. Medical Hypotheses, Volume 180, 2023, 111186, ISSN 0306-9877, https://doi.org/10.1016/j.mehy.2023.111186. https://www.sciencedirect.com/science/article/pii/S0306987723001822 (Full text)