Tag: covid-19

Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina

Abstract:

Objective: Long COVID is a condition characterised by persistent symptoms after a SARS-CoV-2 infection, with neurological manifestations being particularly frequent. Existing research suggests that long COVID patients not only report cognitive symptoms but also exhibit measurable cognitive impairment. Neuroimaging studies have identified structural alterations in brain regions linked to cognitive functions. However, most of these studies have focused on patients within months of their initial infection. This study aims to explore the longer-term cognitive effects and brain structural changes in long COVID patients, approximately two years post-infection, in a cohort from San Martín, Buenos Aires, Argentina.

Methods: We conducted a cross-sectional study involving 137 participants: 109 with long COVID symptoms and 28 healthy controls. The participants underwent an initial clinical assessment, completed a structured questionnaire and standardised scales, underwent a cognitive assessment, and had a brain MRI scan. Structural MRI images were processed via FreeSurfer and FSL to obtain volumetric measures for subcortical and cortical regions, along with regional cortical thickness. Differences between groups for these variables were analysed using ANCOVA, with permutation tests applied to correct for multiple comparisons.

Results: Long COVID patients reported persistent cognitive symptoms such as memory problems and brain fog, with higher levels of fatigue and reduced quality of life compared to controls. Despite subjective cognitive complaints, cognitive tests did not reveal significant differences between groups, except for the TMT-A (p = 0.05). MRI analysis revealed decreased volume in the cerebellum (p = 0.03), lingual gyrus (p = 0.04), and inferior parietal regions (p = 0.03), and reduced cortical thickness in several areas, including the left and right postcentral gyri (p = 0.02, p = 0.03) and precuneus (p = 0.01, p = 0.02).

Conclusions: This study highlights the enduring impact of long COVID on quality of life and physical activity, with specific brain structural changes identified two years post-infection. Although cognitive tests did not show clear impairment, the observed brain atrophy and significant reduction in quality of life emphasize the need for comprehensive interventions and further longitudinal studies to understand the long-term effects of long COVID on cognition and brain health.

Source: Cataldo SA, Micciulli A, Margulis L, Cibeyra M, Defeo S, Horovitz SG, Martino A, Melano R, Mena M, Parisi F, Santoro D, Sarmiento F, Belzunce MA. Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina. BMC Neurol. 2024 Nov 18;24(1):450. doi: 10.1186/s12883-024-03959-8. PMID: 39558250; PMCID: PMC11572126. https://pmc.ncbi.nlm.nih.gov/articles/PMC11572126/ (Full text)

On the Prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after a SARS-CoV-2 infection

Introduction:

There is an increasing body of evidence connecting the post-acute SARS-CoV-2 condition (PASC, commonly known as long COVID) to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating disease of unknown cause characterized by persistent and unexplained fatigue, post-exertional malaise (PEM), among other symptoms. This connection implies that, in the clinic, some PASC cases comply with the official case definitions of ME/CFS. As such, there is a necessity to quantify the burden of ME/CFS among the PASC population in order to delineate effective healthcare interventions for the benefit of these patients who are often neglected or, in some extreme cases, stigmatized by medical staff and society.
To answer this urgent research question, Dehlia and Guthridge performed a systematic review and meta-analysis of recent data on PASC adults and reported an ME/CFS prevalence estimate of 51% (95% CI, 42%-60%); this systematic review and meta-analysis will be referred to as PASC-ME/CFS study. In the present Letter to Editor, we aimed to discuss the reliability of this estimate using the research protocol from the European Network on ME/CFS (EUROMENE) for systematic reviews and meta-analysis on the epidemiology burden of ME/CFS in Europe.

Source: Sepúlveda N, Westermeier F. On the Prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after a SARS-CoV-2 infection. J Infect. 2024 Nov 16:106353. doi: 10.1016/j.jinf.2024.106353. Epub ahead of print. PMID: 39557089. Sepúlveda N, Westermeier F. On the Prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after a SARS-CoV-2 infection. J Infect. 2024 Nov 16:106353. doi: 10.1016/j.jinf.2024.106353. Epub ahead of print. PMID: 39557089. https://www.journalofinfection.com/article/S0163-4453(24)00288-3/fulltext (Full text)

Initiating Long Covid RECOVERy

Introduction:

The coronavirus disease 2019 (COVID-19) pandemic paralyzed the United States, rendering thousands critically ill and ultimately killing more than 1 million Americans. Many survivors, particularly those with adult respiratory distress syndrome, required prolonged rehabilitation. Many more people, including those who did not require hospitalization for their acute illness, presented with a host of other persistent, disabling symptoms. The latter condition was termed “Long Covid” and turned out to be the most prevalent postacute sequelae of the COVID-19 pandemic.

The symptom complex that characterizes Long Covid resembles that seen in other infection-associated chronic conditions, notably overlapping with those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms include fatigue, unrefreshing sleep, neurocognitive dysfunction characterized by impaired executive function, exercise intolerance, fluctuating heart rate and sense of dizziness particularly in the upright position, and postexertional malaise, a signature symptom of ME/CFS. The drivers of these conditions remain unknown, and no treatments have proven effective. Data suggest that many individuals with Long Covid may return to health months or years after onset, but debilitating symptoms and unknown long-term outcomes remain in too many people. Of greatest concern is that, for some individuals, Long Covid may last a lifetime.

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Source: Marrazzo J, Gibbons GH, Koroshetz W. Initiating Long Covid RECOVERy. Sci Transl Med. 2024 Nov 13;16(773):eadr9971. doi: 10.1126/scitranslmed.adr9971. Epub 2024 Nov 13. PMID: 39536123. https://www.science.org/doi/10.1126/scitranslmed.adr9971 (Full text)

Trajectories of functional limitations, health-related quality of life and societal costs in individuals with long COVID: a population-based longitudinal cohort study

Abstract:

Objectives: To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.

Design: A population-based longitudinal cohort study using real-time user data.

Setting: 35 specialised long COVID clinics in the UK.

Participants: 4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.

Main outcome measures: Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.

Results: The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was -0.86 (95% CI -1.32, -0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.

Conclusions: Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.

Source: Wang J, Goodfellow H, Walker S, Blandford A, Pfeffer P, Hurst JR, Sunkersing D, Bradbury K, Robson C, Henley W, Gomes M. Trajectories of functional limitations, health-related quality of life and societal costs in individuals with long COVID: a population-based longitudinal cohort study. BMJ Open. 2024 Nov 13;14(11):e088538. doi: 10.1136/bmjopen-2024-088538. PMID: 39537389. https://bmjopen.bmj.com/content/14/11/e088538 (Full text)

Overlapping conditions in Long COVID at a multisite academic center

Abstract:

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.

Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.

Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).

Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.

Source: Grach SL, Dudenkov DV, Pollack B, Fairweather D, Aakre CA, Munipalli B, Croghan IT, Mueller MR, Overgaard JD, Bruno KA, Collins NM, Li Z, Hurt RT, Tal MC, Ganesh R, Knight DTR. Overlapping conditions in Long COVID at a multisite academic center. Front Neurol. 2024 Oct 25;15:1482917. doi: 10.3389/fneur.2024.1482917. PMID: 39524912; PMCID: PMC11543549. https://pmc.ncbi.nlm.nih.gov/articles/PMC11543549/ (Full text)

Web-based telemedicine approach for treatment of post-COVID-19 in Thuringia (WATCH)

Abstract:

Objective: After infection with SARS-CoV-2, a substantial proportion of patients develop long-lasting sequelae. These sequelae include fatigue (potentially as severe as that seen in ME/CFS cases), cognitive dysfunction, and psychiatric symptoms. Because the pathophysiology of these sequelae remains unclear, existing therapeutic concepts address the symptoms through pacing strategies, cognitive training, and psychological therapy.

Methods: Here, we present a protocol for a digital multimodal structured intervention addressing common symptoms through three intervention modules: BRAIN, BODY, and SOUL. This intervention includes an assessment conducted via a mobile “post-COVID-19 bus” near the patient’s home, as well as the use of wearable devices and mobile applications to support pacing strategies and collection of data, including ecological momentary assessment.

Results: We will focus on physical component subscore of the SF36 as Quality of Life parameter as the primary outcome parameter for WATCH to take into account the holistic approach that is necessary for care of post-COVID patients.

Conclusion: In the current project, we present a protocol for a holistic and multimodal structured therapeutic concept which is easily accessible, and scalable for post-COVID patients.

Source: Reuken PA, Besteher B, Bleidorn J, Brockmann D, Finke K, Freytag A, Lehmann-Pohl K, Lemhöfer C, Mikolajczyk R, Puta C, Scherag A, Wiedermann M, Zippel-Schultz B, Stallmach A. Web-based telemedicine approach for treatment of post-COVID-19 in Thuringia (WATCH). Digit Health. 2024 Oct 14;10:20552076241291748. doi: 10.1177/20552076241291748. PMID: 39493638; PMCID: PMC11528766. https://pmc.ncbi.nlm.nih.gov/articles/PMC11528766/ (Full text)

Two-Day Cardiopulmonary Exercise Testing in Long COVID Post-Exertional Malaise Diagnosis

Abstract:

Background: Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients.

Methods: 15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; BMI = 32.2(8.5) kg/m2] performed a pulmonary function test and two ramp-incremental CPETs separated by 24hr. CPET variables included gas exchange threshold (GET), V̇O2peak and WRpeak. Ratings of perceived dyspnoea and leg effort were recorded at peak exercise using the modified 0-10 Borg Scale. PEM (past six months) was assessed using the modified DePaul Symptom Questionnaire (mDSQ). One-sample t-tests were used to test significance of mean difference between days (p<0.05).

Results: mDSQ revealed PEM in 80% of patients. Lung function was normal. Responses to day 1 CPET were consistent with the presence of aerobic deconditioning in 40% of patients (V̇O2peak <80% predicted, in the absence of evidence of cardiovascular and pulmonary limitations). There were no differences between day-1 and day-2 CPET responses (all p>0.05).

Conclusion: Post exertional malaise symptoms in Long COVID patients, in the absence of differences in two-day CPET responses separated by 24hours, suggests that post-exertional malaise is not due to impaired recovery of exercise capacity between days.

Source: Gattoni C, Abbasi A, Ferguson C, Lanks CW, Decato TW, Rossiter HB, Casaburi R, Stringer WW. Two-Day Cardiopulmonary Exercise Testing in Long COVID Post-Exertional Malaise Diagnosis. Respir Physiol Neurobiol. 2024 Oct 25:104362. doi: 10.1016/j.resp.2024.104362. Epub ahead of print. PMID: 39490617. https://www.sciencedirect.com/science/article/pii/S1569904824001551 (Full text)

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 substrate 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 (V˙˙O2) at maximum fat oxidation (g 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: Ramírez-Vélez R, Oscoz-Ochandorena S, García-Alonso Y, García-Alonso N, Legarra-Gorgoñon G, Oteiza J, Lorea AE, Izquierdo M, Correa-Rodríguez M. Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation analysis. Clin Nutr ESPEN. 2023 Dec;58:253-262. doi: 10.1016/j.clnesp.2023.10.009. Epub 2023 Oct 14. PMID: 38057014. https://clinicalnutritionespen.com/article/S2405-4577(23)02166-6/fulltext (Full text)

Respiratory SARS-CoV-2 Infection Causes Skeletal Muscle Atrophy and Long-Lasting Energy Metabolism Suppression

Abstract:

Muscle fatigue represents the most prevalent symptom of long-term COVID, with elusive pathogenic mechanisms. We performed a longitudinal study to characterize histopathological and transcriptional changes in skeletal muscle in a hamster model of respiratory SARS-CoV-2 infection and compared them with influenza A virus (IAV) and mock infections.

Histopathological and bulk RNA sequencing analyses of leg muscles derived from infected animals at days 3, 30, and 60 post-infection showed no direct viral invasion but myofiber atrophy in the SARS-CoV-2 group, which was accompanied by persistent downregulation of the genes related to myofibers, ribosomal proteins, fatty acid β-oxidation, tricarboxylic acid cycle, and mitochondrial oxidative phosphorylation complexes.

While both SARS-CoV-2 and IAV infections induced acute and transient type I and II interferon responses in muscle, only the SARS-CoV-2 infection upregulated TNF-α/NF-κB but not IL-6 signaling in muscle. Treatment of C2C12 myotubes, a skeletal muscle cell line, with combined IFN-γ and TNF-α but not with IFN-γ or TNF-α alone markedly impaired mitochondrial function.

We conclude that a respiratory SARS-CoV-2 infection can cause myofiber atrophy and persistent energy metabolism suppression without direct viral invasion. The effects may be induced by the combined systemic interferon and TNF-α responses at the acute phase and may contribute to post-COVID-19 persistent muscle fatigue.

Source: Homma ST, Wang X, Frere JJ, Gower AC, Zhou J, Lim JK, tenOever BR, Zhou L. Respiratory SARS-CoV-2 Infection Causes Skeletal Muscle Atrophy and Long-Lasting Energy Metabolism Suppression. Biomedicines. 2024 Jun 28;12(7):1443. doi: 10.3390/biomedicines12071443. PMID: 39062017; PMCID: PMC11275164. https://pmc.ncbi.nlm.nih.gov/articles/PMC11275164/ (Full text)

Persistent Fatigue, Weakness, and Aberrant Muscle Mitochondria in Survivors of Critical COVID-19

Abstract:

Objectives: Persistent skeletal muscle dysfunction in survivors of critical illness due to acute respiratory failure is common, but biological data elucidating underlying mechanisms are limited. The objective of this study was to elucidate the prevalence of skeletal muscle weakness and fatigue in survivors of critical illness due to COVID-19 and determine if cellular changes associate with persistent skeletal muscle dysfunction.

Design: A prospective observational study in two phases: 1) survivors of critical COVID-19 participating in physical outcome measures while attending an ICU Recovery Clinic at short-term follow-up and 2) a nested cohort of patients performed comprehensive muscle and physical function assessments with a muscle biopsy; data were compared with non-COVID controls.

Setting: ICU Recovery Clinic and clinical laboratory.

Patients/subjects: Survivors of critical COVID-19 and non-COVID controls.

Interventions: None.

Measurements and main results: One hundred twenty patients with a median of 56 years old (interquartile range [IQR], 42-65 yr old), 43% female, and 33% individuals of underrepresented race attended follow-up 44 ± 17 days after discharge. Patients had a median Acute Physiology and Chronic Health Evaluation-II score of 24.0 (IQR, 16-29) and 98 patients (82%) required mechanical ventilation with a median duration of 14 days (IQR, 9-21 d). At short-term follow-up significant physical dysfunction was observed with 93% of patients reporting generalized fatigue and performing mean 218 ± 151 meters on 6-minute walk test (45% ± 30% of predicted). Eleven patients from this group agreed to participate in long-term assessment and muscle biopsy occurring a mean 267 ± 98 days after discharge. Muscle tissue from COVID exhibited a greater abundance of M2-like macrophages and satellite cells and lower activity of mitochondrial complex II and complex IV compared with controls.

Conclusions: Our findings suggest that aberrant repair and altered mitochondrial activity in skeletal muscle associates with long-term impairments in patients surviving an ICU admission for COVID-19.

Source: Mayer KP, Ismaeel A, Kalema AG, Montgomery-Yates AA, Soper MK, Kern PA, Starck JD, Slone SA, Morris PE, Dupont-Versteegden EE, Kosmac K. Persistent Fatigue, Weakness, and Aberrant Muscle Mitochondria in Survivors of Critical COVID-19. Crit Care Explor. 2024 Oct 16;6(10):e1164. doi: 10.1097/CCE.0000000000001164. PMID: 39412208; PMCID: PMC11487221. https://pmc.ncbi.nlm.nih.gov/articles/PMC11487221/ (Full text)