Tag: long covid fatigue

Long COVID: Plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms

Abstract:

It is well known the potential of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection to induce post-acute sequelae, a condition called Long COVID. This syndrome includes several symptoms, but the central nervous system (CNS) main one is neurocognitive dysfunction. Recently it has been demonstrated the relevance of plasma levels of neurofilament light chain (pNfL), as a biomarker of early involvement of the CNS in COVID-19.

The aim of this study was to investigate the relationship between pNfL in patients with post-acute neurocognitive symptoms and the potential of NfL as a prognostic biomarker in these cases. A group of 63 long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the long COVID assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays. Levels of pNfL were significantly higher in long COVID patients with neurocognitive symptoms when compared to HC (p = 0.0031).

Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive lost and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively). Previous reports suggested that pNfL levels are related with higher risk of severity and predict lethality of COVID-19.

Our findings demonstrate that SARS-CoV-2 infection seems to have a long-term impact on the brain, even in patients who presented mild acute disease. NfL measurements might be useful to identify CNS involvement in long COVID associated with neurocognitive symptoms and to identify who will need continuous monitoring and treatment support.

Source: Gutman E, Salvio A, Fernandes R, et al. Long COVID: Plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms. Research Square; 2023. DOI: 10.21203/rs.3.rs-2921879/v1. https://www.researchsquare.com/article/rs-2921879/v1 (Full text)

Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19

Abstract:

A growing number of patients with SARS-CoV-2 infections experience long-lasting symptoms. Even patients who suffered from a mild acute infection show a variety of persisting and debilitating neurocognitive, respiratory, or cardiac symptoms (Long-Covid syndrome), consequently leading to limitations in everyday life. Because data on health-related quality of life (HRQoL) is scarce, we aimed to characterize the impact of Long-Covid symptoms after a mild or moderate acute infection on HRQoL.

In this observational study, outpatients seeking counseling in the interdisciplinary Post-Covid consultation of the University Hospital Zurich with symptoms persisting for more than 4 weeks were included. Patients who received an alternative diagnosis or suffered from a severe acute Covid-19 infection were excluded. St. George’s Respiratory Questionnaire (SGRQ), Euroquol-5D-5L (EQ-5D-5L), and the Short form 36 (SF-36) were distributed to assess HRQoL. 112 patients were included, 86 (76.8%) were female, median (IQR) age was 43 (32.0, 52.5) years with 126 (91, 180) days of symptoms.

Patients suffered frequently from fatigue (81%), concentration difficulties (60%), and dyspnea (60%). Patients mostly stated impairment in performing usual activities and having pain/discomfort or anxiety out of the EQ-5D-5L. EQ index value and SGRQ activity score component were significantly lower in females. SF-36 scores showed remarkably lower scores in the physical health domain compared to the Swiss general population before and during the COVID-19 pandemic.

Long-Covid syndrome has a substantial impact on HRQoL. Long-term surveillance of patients must provide clarity on the duration of impairments in physical and mental health.

Trial registration: The study is registered on www.ClinicalTrials.gov , NCT04793269.

Source: Malesevic S, Sievi NA, Baumgartner P, Roser K, Sommer G, Schmidt D, Vallelian F, Jelcic I, Clarenbach CF, Kohler M. Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19. Sci Rep. 2023 May 12;13(1):7717. doi: 10.1038/s41598-023-34678-8. PMID: 37173355; PMCID: PMC10175927. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175927/ (Full text)

Co-production of a feasibility trial of pacing interventions for Long COVID

Abstract:

Background: The high incidence of COVID-19 globally has led to a large prevalence of Long COVID but there is a lack of evidence-based treatments. There is a need to evaluate existing treatments for symptoms associated with Long COVID. However, there is first a need to evaluate the feasibility of undertaking randomised controlled trials of interventions for the condition. We aimed to co-produce a feasibility study of non-pharmacological interventions to support people with Long COVID.

Methods: A consensus workshop on research prioritisation was conducted with patients and other stakeholders. This was followed by the co-production of the feasibility trial with a group of patient partners, which included the design of the study, the selection of interventions, and the production of dissemination strategies.

Results: The consensus workshop was attended by 23 stakeholders, including six patients. The consensus from the workshop was to develop a clinical trial platform that focused on testing different pacing interventions and resources. For the co-production of the feasibility trial, patient partners selected three pacing resources to evaluate (video, mobile application, and book) and co-designed feasibility study processes, study materials and undertook usability testing of the digital trial platform.

Conclusion: In conclusion, this paper reports the principles and process used to co-produce a feasibility study of pacing interventions for Long COVID. Co-production was effective and influenced important aspects of the study.

Source: Turner GM, McMullan C, Aiyegbusi OL, Hughes SE, Walker A, Jeyes F, Adler Y, Chong A, Buckland L, Stanton D, Davies EH, Haroon S, Calvert M. Co-production of a feasibility trial of pacing interventions for Long COVID. Res Involv Engagem. 2023 Mar 30;9(1):18. doi: 10.1186/s40900-023-00429-2. PMID: 36997975; PMCID: PMC10061378. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061378/ (Full text)

Physical activity levels respiratory and peripheral muscle strength and pulmonary function in young post-COVID-19 patients : A cross-sectional study

Abstract:

Objective: Coronavirus disease 2019 (COVID-19) causes permanent problems, even mild severity. The long-term consequences of COVID-19 are still unknown. This study aimed to investigate physical activity levels, respiratory and peripheral muscle strength, and pulmonary function in the long term in young adult COVID-19 patients who recovered from mild disease.

Methods: This cross-sectional study was carried out at least 6 months after the COVID-19 diagnosis, 54 patients with COVID-19 (median age: 20 years) and 46 controls (median age: 21 years) were compared. Functional status (post-COVID-19 functional status scale), respiratory (maximum inspiratory and expiratory pressures (MIP, MEP)) and peripheral muscle strength (dynamometer), pulmonary function (Spirometry), dyspnea and fatigue (modified Borg scale), and physical activity levels (International Physical Activity Questionnaire) were evaluated.

Clinicaltrial number: NCT05381714.

Results: Patients with COVID-19 measured and percent predicted MIP and MEP were statistically decreased compared with the controls (p < 0.05). Shoulder abductors muscle strength (p < 0.001) and the number of individuals with low physical activity levels were significantly higher in patients compared with controls (p = 0.048). Pulmonary function, quadriceps muscle strength, exertional dyspnea, and fatigue scores were similar in groups (p > 0.05).

Conclusion: Respiratory and peripheral muscle strength and physical activity levels are adversely affected in patients with COVID-19, even though the patients were mildly affected in the long term. Also, symptoms such as dyspnea and fatigue may persist. Therefore, these parameters should be evaluated in the long term, even in young adults who are mildly affected by COVID-19.

Source: Güneş M, Yana M, Güçlü MB. Physical activity levels respiratory and peripheral muscle strength and pulmonary function in young post-COVID-19 patients : A cross-sectional study. Wien Klin Wochenschr. 2023 May;135(9-10):251-259. doi: 10.1007/s00508-023-02204-5. Epub 2023 Apr 28. PMID: 37115337; PMCID: PMC10141881. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141881/ (Full text)

Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study

Abstract:

To describe the prevalence of long COVID in children infected for the first time (n=332) or reinfected (n=243) with Omicron variant SARS-CoV-2, compared with test-negative children (n=311). 12-16% infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first-positive and reinfection (pchi-square=0.17).

Source: Pinto Pereira SM, Mensah A, Nugawela MD, Stephenson T, Ladhani SN, Dalrymple E, Dudley J, McOwat K, Simmons R, Heyman I, Segal T, Semple MG, Xu L, Shafran R; CLoCk Consortium. Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study. J Pediatr. 2023 May 10:113463. doi: 10.1016/j.jpeds.2023.113463. Epub ahead of print. PMID: 37172813; PMCID: PMC10171900. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171900/ (Full text)

Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study

Abstract:

Fatigue is one of the most frequent and disabling symptoms of the post-COVID syndrome. In this study, we aimed to assess the effects of transcranial direct current stimulation on fatigue severity in a group of patients with post-COVID syndrome and chronic fatigue.

We conducted a double-blind, parallel-group, sham-controlled study to evaluate the short-term effects of anodal transcranial direct current stimulation (2 mA, 20 min/day) on the left dorsolateral prefrontal cortex. The modified fatigue impact scale score was used as the primary endpoint. Secondary endpoints included cognition (Stroop test), depressive symptoms (Beck depression inventory) and quality of life (EuroQol-5D).

Patients received eight sessions of transcranial direct current stimulation and were evaluated at baseline, immediately after the last session, and one month later. Forty-seven patients were enrolled (23 in the active treatment group and 24 in the sham treatment group); the mean age was 45.66 ± 9.49 years, and 37 (78.72%) were women. The mean progression time since the acute infection was 20.68 ± 6.34 months.

Active transcranial direct current stimulation was associated with a statistically significant improvement in physical fatigue at the end of treatment and 1 month as compared with sham stimulation. No significant effect was detected for cognitive fatigue.

In terms of secondary outcomes, active transcranial direct current stimulation was associated with an improvement in depressive symptoms at the end of treatment. The treatment had no effects on the quality of life. All the adverse events reported were mild and transient, with no differences between the active stimulation and sham stimulation groups.

In conclusion, our results suggest that transcranial direct current stimulation on the dorsolateral prefrontal cortex may improve physical fatigue. Further studies are needed to confirm these findings and optimize stimulation protocols.

Source: Oliver-Mas S, Delgado-Alonso C, Delgado-Álvarez A, Díez-Cirarda M, Cuevas C, Fernández-Romero L, Matias-Guiu A, Valles-Salgado M, Gil-Martínez L, Gil-Moreno MJ, Yus M, Matias-Guiu J, Matias-Guiu JA. Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study. Brain Commun. 2023 Apr 10;5(2):fcad117. doi: 10.1093/braincomms/fcad117. PMID: 37091591; PMCID: PMC10116605. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116605/ (Full text)

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study

Summary:

Background: ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID.

Methods: Patients with fatigue dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by 31P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849.

Findings: Between December 15th 2021, and May 23th 2022, 60 participants were screened and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] −4.30, 95% confidence interval (95% CI) −7.14, −1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious, or led to treatment discontinuation.

Interpretation: Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there was a significant improvement in fatigue-based symptoms among patients living with Long COVID following a four week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID.

Source: Lucy E.M. Finnigan, Mark Philip Cassar, Margaret James Koziel, Joel Pradines, Hanan Lamlum, Karim Azer, et al. Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study. The Lancet, Published: April 14, 2023 DOI: https://doi.org/10.1016/j.eclinm.2023.101946 (Full text)

Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms

Abstract:

Acute infections with SARS-CoV-2 variants of concerns (VOCs) differ in clinical presentation. Discrepancies in their long-term sequelae, commonly referred to as long COVID, however, remain to be explored. We retrospectively analyzed data of 287 patients presented at the post-COVID care of the Pulmonology Department, Semmelweis University, Budapest, Hungary, and infected with SARS-CoV-2 during a period of 3 major epidemic waves in Hungary (February-July 2021, VOC: B.1.1.7, Alpha, N = 135; August-December 2021, VOC: B.1.617.2, Delta, N = 89; and January-June 2022, VOC: B.1.1.529, Omicron; N = 63), > 4 weeks after acute COVID-19.

Overall, the ratio of long COVID symptomatic (LC) and asymptomatic (NS) patients was 2:1. Self-reported questionnaires on fatigue (Fatigue Severity Scale, FSS), sleepiness (Epworth Sleepiness Scale, ESS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) showed higher scores for LC (4.79 ± 0.12, 7.45 ± 0.33 and 7.46 ± 0.27, respectively) than NS patients (2.85 ± 0.16, 5.23 ± 0.32 and 4.26 ± 0.29, respectively; p < 0.05 for all vs. LC). By comparing data of the three waves, mean FSS and PSQI scores of LC patients, but not ESS scores, exceeded the normal range in all, with no significant inter-wave differences.

Considering FSS ≥ 4 and PSQI > 5 cutoff values, LC patients commonly exhibited problematic fatigue (≥ 70%) and poor sleep quality (> 60%) in all three waves. Comparative analysis of PSQI component scores of LC patients identified no significant differences between the three waves.

Our findings highlight the importance of concerted efforts to manage both fatigue and sleep disturbances in long COVID patient care. This multifaceted approach should be followed in all cases infected with either VOCs of SARS-CoV-2.

Source: Percze AR, Nagy A, Polivka L, Barczi E, Czaller I, Kovats Z, Varga JT, Ballai JH, Muller V, Horvath G. Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms. Inflammopharmacology. 2023 Apr 5:1–7. doi: 10.1007/s10787-023-01190-4. Epub ahead of print. PMID: 37020055; PMCID: PMC10075170. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075170/ (Full text)

Long COVID symptoms, pathophysiology and possible mechanisms: Still, we are learning!

Abstract:
Long COVID is an unpredicted sequel of COVID-19 disease documented nearly in half cases globally. Long COVID is multisystem syndrome with nonspecific symptoms and organic signs of unidentified pathology occurs after COVID-19 disease. Long COVID symptoms has been documented in some cases irrespective of disease severity or hospitalization. Long COVID symptoms has significant impact on quality of life in those cases suffered from disease in recent past and lingering to almost two years since infection.
Importantly, not all cases of COVID-19 were shown long COVID symptoms. Most common long COVID symptoms (ten in number) as joint pain, fatigability, chest discomfort, shortness of breath, hair loss, chest pain, weight gain, anxiety/depression & memory impairment. Pathophysiology resulting into long COVID manifestations is still not completely validated.
Researchers have reported ‘immune dysregulation’ and ‘coagulation abnormalities’ are probable pathophysiological mechanism for long COVID. Some of the long COVID effects shown complete reversibility including post COVID lung fibrosis. Reboot system to restore immune dysregulation and recovery in long COVID is real concern. Long COVID symptoms cases are more health conscious and usually follows pattern of doctor shopping due to underestimation by family physicians either due to lack of suspicion or lack of knowledge regarding treatment protocol.
Source: Shital Patil, Sanika Narkar, Jayashree Dahiphale, Vipul Raka, Shubham Choudhari. and Gajanan Gondhali. Long COVID symptoms, pathophysiology and possible mechanisms: Still, we are learning! World Journal of Advanced Pharmaceutical and Medical Research, 2023, 04(01), 053–065. https://zealjournals.com/wjapmr/content/long-covid-symptoms-pathophysiology-and-possible-mechanisms-still-we-are-learning (Full text available as PDF file)

Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19 infection

Abstract:

Objective and design: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is a major symptom of the long-COVID syndrome. The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19 infection.

Subjects and methods: We tested this hypothesis by analysing pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19 positive and COVID-19 negative participants were categorized based on antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale.

Results: COVID-19 positive participants exhibited mild symptoms of infection. Chronic fatigue was a prevalent symptom among this population and was significantly higher in the COVID-19 positive participants than COVID-19 negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in COVID-19 positive and COVID-19 negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in COVID-19 negative, but not COVID-19 positive
individuals. Raised BMI was associated with chronic fatigue in COVID-19 positive participants.

Conclusions: We found evidence that pre-existing increased levels of IL-6 provide the ground for chronic fatigue symptoms but there was no specific link seen with mild COVID-19 status. Elevated BMI increased the risk of chronic fatigue in mild COVID-19 infection consistent with previous reports.

Source: B Freidin, M., Borsini, A., Pariante, C., & MK Williams, F. (2023). Long-COVID fatigue is not predicted by prepandemic plasma IL-6 levels in mild COVID-19 infection. Inflammation Research. https://kclpure.kcl.ac.uk/portal/files/201594849/Freidin_et_al._2023.pdf (Full text)