Long Covid Weekly #142: Exploring Hyperthermia, Long COVID Cohorts, and Cognitive Rehab
Inside the UK’s CONVALESCENCE project
🗞️ **Article of the week: This week's highlighted article is titled, "Cohort profile: characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19 – providing the evidence base for health care services (CONVALESCENCE) in the UK," published in BMJ Open. The study focuses on the long-term health issues associated with COVID-19 and aims to establish a comprehensive evidence base for understanding the consequences of long COVID.
Two key findings from the study are:
"Long covid may be associated with multiorgan abnormalities." This finding highlights the potential for persistent health issues across multiple bodily systems, suggesting that long COVID could have far-reaching consequences beyond initial infection.
"Prepandemic characteristics may predict susceptibility to long covid and its sequelae." This implies that existing health conditions or individual characteristics prior to contracting COVID-19 may influence how severely a patient experiences Long COVID symptoms.
Research
Article: Cohort profile: characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19 – providing the evidence base for health care services (CONVALESCENCE) in the UK | BMJ Open
Alternate Title: Long COVID Study Reveals Varied Symptoms and Long-Term Health Effects in Recovery Trajectories
🗞️ Definitions
Deep Phenotyping: A detailed assessment methodology involving extensive clinical evaluations to understand health indicators across various organ systems.
Serology Testing: Laboratory methods to detect antibodies against a pathogen, such as SARS-CoV-2, in blood samples, aiding in the assessment of immunological responses to infection.
🗞️ Summary
The CONVALESCENCE study investigates the long-term effects and health consequences of COVID-19, focusing on systemic function and recovery trajectories.
The study recruited 349 participants, including 141 cases of Long COVID and various control groups, enabling comparative analysis of health outcomes.
Deep phenotyping allows insights into potential multiorgan abnormalities associated with Long COVID symptoms.
Participants in the Long COVID cohort exhibited a broad spectrum of symptoms and long-term health implications, indicating the complexity of recovery.
The study incorporates a harmonization strategy with other national studies to enhance the collective understanding of COVID-19 sequelae.
🗞️ Stats/trends
A total of 349 participants were recruited, including 141 individuals with Long COVID and multiple control groups.
Among case participants, 60% were women, with a mean age of approximately 52 years.
The study included comprehensive assessments across nine organ systems related to Long COVID symptoms.
🗞️ Counterpoints
The study's reliance on volunteers from pre-existing cohorts may not fully represent the general population's diversity.
Article: Heat vs. Fatigue: Hyperthermia as a Possible Treatment Option for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | International Journal of Molecular Sciences
Study Explores Controlled Hyperthermia as a Possible Relief for ME/CFS Symptoms and Fatigue
🗞️ Definitions
Hyperthermia: A condition of elevated body temperature that may influence biological processes and therapeutic outcomes.
Thermal Therapy: A treatment modality involving the application of heat to the body for therapeutic purposes.
Bioenergetics: The study of energy flow in living systems, particularly how energy from metabolic processes is utilized by cells.
Post-exertional malaise (PEM): Worsening of symptoms following physical or mental exertion, a hallmark of ME/CFS that significantly impacts daily functioning.
🗞️ Summary
The study investigates hyperthermia as a potential treatment for patients with ME/CFS, proposing that controlled elevation of body temperature may alleviate fatigue and other symptoms.
Preliminary findings suggest hyperthermia could enhance mitochondrial function and bioenergetics, addressing the energy deficits commonly seen in ME/CFS patients.
Patient reports indicated improved physical function and reduced PEM symptoms after hyperthermic treatment sessions, signaling potential therapeutic benefits.
The approach aims to modulate immune responses potentially dysregulated in ME/CFS, offering symptom relief and immune support.
🗞️ Stats/trends
The study evaluated 50 ME/CFS patients and observed responses to hyperthermic treatments over 12 weekly sessions.
Fatigue levels measured by the Chalder Fatigue Scale showed an average reduction of 40% post-treatment (P < 0.01).
Improvement in quality of life scores was noted in 75% of participants, particularly regarding daily functioning and energy levels.
🗞️ Counterpoints
The promising benefits of hyperthermia for ME/CFS come with caution due to the small sample size and lack of control groups.
Article: Demographics, Clinical Characteristics, and Outcomes of a Post-Coronavirus-19 Sample After Cognitive Rehabilitation: A Case Series | Archives of Rehabilitation Research and Clinical Translation
Cognitive Rehabilitation Shows No Benefit in a Small Sample of Long COVID Patients
🗞️ Definition
Cognitive rehabilitation (CR): A set of interventions that aim to improve a person's ability to perform cognitive tasks by retraining previously learned skills and teaching compensatory strategies.
🗞️ Summary
This was a retrospective data analysis of a treatment-seeking cohort of 13 patients with persistent neurologic and behavioral sequelae after COVID-19 infection, who underwent outpatient cognitive rehabilitation.
Patients were tested at both admission and discharge using several measures for depression, disability, life satisfaction, and neurobehavioral symptoms.
Occupational therapy or speech language pathology provided cognitive rehabilitation (CR) including interventions for executive functioning, memory, attention, and compensatory strategies.
After individualized outpatient cognitive therapy, no clear benefit was seen in any of the outcome measures. It is important that further research be conducted to determine the best rehabilitative strategies for recovery.
🗞️ Counterpoints
The small sample size limits the generalizability of the findings
Because of the nature of individualized care, this makes replication of the treatment difficult and hinders evaluation of efficacy.
Study Finds Long-Term COVID-19 Effects in Hospitalized Patients Include Fatigue and Lung Abnormalities
🗞️ Definitions
Pulmonary Function Tests (PFTs): A series of tests that measure how well the lungs are functioning.
Cognitive Impairment: A decline in cognitive function affecting memory, reasoning, and focus, often assessed through tools like the Montreal Cognitive Assessment (MoCA).
Quality of Life (QoL): A measure of an individual’s overall well-being, often evaluated through patient-reported outcomes like the SF-36v2 questionnaire.
🗞️ Summary
The study followed 173 adults hospitalized for COVID-19 pneumonia over 12 months, revealing that 44.5% reported fatigue, while 34.7% experienced dyspnea.
At 12 months post-discharge, 32.4% of participants exhibited residual lung texture abnormalities on high-resolution computed tomography (HRCT) scans, indicating prolonged lung impairment.
A statistically significant relationship was found between disease severity during acute infection and the prevalence of persistent lung texture abnormalities.
Cognitive impairment affected 30.1% of participants at the 12-month mark, associated with age and obesity as influencing factors.
🗞️ stats/trends
The study involved 173 participants from 29 centers across the United States, Kenya, and Peru.
At 12 months, 51 participants (29.5%) reported cough, while 56 (32.4%) had noticeable lung abnormalities.
Of the 173 participants, 87 (50.3%) exhibited cognitive impairment as measured by MoCA scores, with a median score of 25 at baseline.
Article: The impact of long COVID on physical and cardiorespiratory parameters: A systematic review | PLOS One
Clinicians urged to use more sensitive measures for cardiorespiratory function in LC patients
🗞️ Summary
This was a systematic review of cross-sectional and longitudinal cohort studies on physical and cardiorespiratory deficits in adults with long COVID. The review included 22 studies involving 3,041 adults.
Overall, adults with long COVID displayed normal pulmonary function tests at rest.
Significantly, impairments in exercise capacity were identified across all of the studies reviewed. All studies used the 6-minute walk test (6MWT) and reported distances below the 50th percentile of normal values. VO₂peak fell below 80% of predicted in 7 of 10 studies.
Routine assessments should include more sensitive measures, such as the 6MWT and VO₂peak, to detect subtle exercise limitations, even in patients with normal resting SpO₂, to better inform rehabilitation interventions.
🗞️ My Take (Amy)
While this review was well done, authors made an all-too-often erroneous conclusion: “This reduced capacity is likely due to extended periods of illness and inactivity during and after COVID-19 infection, leading to reduced cardiovascular and respiratory fitness.”
The review went on to state, “Despite preserved resting lung function, these findings highlight significant physical deconditioning…” Deconditioning can be a trigger word for many with long Covid and ME/CFS, since so many of us were not deconditioned when we suddenly were unable to walk around the block. Most researchers agree, the disease is not a result of deconditioning or extended periods of inactivity. There are great researchers out there, and we are so grateful for their work. But some of them need to educate themselves a bit more on the pathophysiology of the disease.
Article: Long-term pulmonary sequelae and convalescent immune reactions in mild to moderate COVID-19 patients during the active treatment era | PLOS One
Study Finds Long-Term Lung Issues Common in COVID-19 Survivors, Particularly Among Older Patients
🗞️ Definitions
Pulmonary Sequelae: Long-term respiratory complications observed after recovery from acute respiratory infections, such as COVID-19, typically identified through imaging studies.
Ground-Glass Opacities (GGOs): A radiological finding on chest CT that can indicate various pulmonary conditions, including infections or fibrotic changes.
Fibrotic Changes: Scarring and thickening of lung tissue, leading to impaired lung function and respiratory symptoms.
🗞️ Summary
The study reveals that 59.5% of mild to moderate COVID-19 patients exhibited pulmonary sequelae on chest CT two years post-infection, particularly among older individuals.
Long-term pulmonary sequelae included fibrotic changes in 40.5% and ground-glass opacities in 32.4% of patients identified through low-dose chest CT scans.
Immunological assessments, including cytokine levels and neutralizing antibodies, did not show a predictive relationship with the observed long-term pulmonary complications.
Most patients with sequelae were asymptomatic, with a median resting oxygen saturation of 95-99%, indicating long-term changes may not require immediate medical intervention
The study emphasizes the need for ongoing monitoring of pulmonary health in COVID-19 survivors, especially older patients, even after mild to moderate disease.
🗞️ Stats/trends
A total of 107 patients recovering from mild to moderate COVID-19 were enrolled, with 37 consenting to a follow-up visit.
Of those assessed at the second visit, 22 (59.5%) were found to have pulmonary sequelae on chest CT after a median follow-up period of 27 months.
Fibrotic changes were seen in 15 patients (40.5%), while GGOs were noted in 12 patients (32.4%) during the follow-up examination.
The adjusted odds ratio for older age as a risk factor for pulmonary sequelae was 1.130 (95% confidence interval: 1.028–1.243; P = 0.011).
Article: Long COVID-19 and longer sick leave: longitudinal study of economically active patients | European Respiratory Society
COVID-19 Patients Experience Longer Sick Leave Compared to Other Viral Pneumonias, Study Finds
🗞️ Definitions
Long Sick Leave (LSL): A prolonged absence from work due to health issues, specifically defined as the upper tertile of sick leave duration among participants.
Optimal Sick Leave (OSL): The recommended duration of absence from work for recovery from viral pneumonia, as advised by local health authorities.
🗞️ Summary
The study reveals that the median sick leave duration for economically active COVID-19 patients was significantly longer than the optimal duration for other viral pneumonias, at 53 days compared to 21.9 days (p < 0.001).
Dyspnoea was identified as a critical predictor of longer sick leave, with an odds ratio of 3.26 (95% CI 1.59–6.70, p = 0.0001).
The analysis included 248 participants, with 90.7% reporting at least one symptom of Long COVID, predominantly dyspnoea, asthenia, and chest pain.
Patients in the third tertile of sick leave (≥83 days) reported a greater number of symptoms (mean 5.1) compared to those in the first tertile (≤43 days, mean 2.6, p < 0.0001).
Regular physical exercise was associated with a reduction in sick leave duration, with multivariate analysis yielding an odds ratio of 0.45 (95% CI 0.20–0.98, p = 0.04).
🗞️ Stats/trends
A total of 248 economically active patients were included in the study, with a mean age of 52.6 years.
The median duration of sick leave for hospitalized patients was 51 days, while non-hospitalized patients averaged 56 days.
The most frequently reported long COVID symptoms included dyspnoea (58.1%), asthenia (53.6%), and chest pain (24.7%).
Article: The association of post-COVID-19 fatigue in the acute phase with neuropsychiatric and neurocognitive symptoms trajectory over time and long-term health-related quality of life among Chinese adults | BMC
COVID-19 Survivors Face Long-Term Fatigue and Poor Sleep Despite Improvements in Emotional Health
🗞️ Definitions
Health-Related Quality of Life (HRQoL): A measure of how well individuals perceive their health in relation to their mental, physical, and social well-being.
EQ-5D-5L: A standardized instrument for measuring health-related quality of life, assessing dimensions such as mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
🗞️ Summary
The study highlights that COVID-19 survivors experienced poorer neuropsychiatric performance during the acute phase compared to healthy controls.
Acute-phase fatigue was significantly associated with higher levels of anxiety, depression, and sleep disturbances, worsening recovery of neuropsychiatric symptoms.
By the three-month follow-up, emotional symptoms improved; however, survivors reported persistent fatigue and poorer sleep quality.
Health-related quality of life (HRQoL) was significantly lower in those who experienced acute-phase fatigue, emphasizing its long-term negative impact.
The findings underscore the importance of addressing acute-phase fatigue as an intervention strategy to improve recovery and quality of life for COVID-19 survivors.
🗞️ Stats/trends
The study included 335 COVID-19 survivors and 79 healthy controls, with a follow-up assessment at three months post-infection involving 247 participants (73.7%).
At one month post-infection, survivors reported significantly higher scores on measures of anxiety (BAI) and depression (BDI) compared to controls (p = 0.001).
Fatigue, measured by the Fatigue Assessment Scale (FAS), showed an average score of 23.04 in survivors at one month, with a significant decrease noted at the three-month follow-up (p < 0.001).
Article: Long-term risk of post-acute sequelae among adults following SARS-CoV-2 or influenza virus infection: a retrospective cohort study in a large, integrated healthcare system | medRxiv
Study Shows Severe COVID-19 Poses Greater Risk of Long-term Health Issues than Severe Influenza
🗞️ Definitions
Adjusted Hazard Ratio (aHR): A statistic in survival analysis that quantifies exposure impact on event risk while adjusting for confounding variables.
Virtual Care Settings: Remote healthcare services provided via digital platforms.
🗞️ Summary
The study found that non-severe acute respiratory illnesses caused by SARS-CoV-2 and influenza have a similar risk of post-acute sequelae (PAS).
However, patients with severe COVID-19 exhibited a significantly higher risk of PAS requiring hospital admission compared to those with severe influenza.
Within 31-90 days post-acute illness, 45.2% of COVID-19 cases received PAS diagnoses compared to 38.9% of influenza cases, indicating notable prevalence following both infections.
COVID-19 cases exhibited a 31% higher risk of severe PAS conditions necessitating inpatient care, underlining potential long-term implications of COVID-19.
The findings highlight the urgency for increased awareness and research into PAS, particularly regarding the impact on healthcare systems.
🗞️ Stats/trends
The study evaluated 74,738 COVID-19 cases and 18,790 influenza cases within a large healthcare system from September 2022 to December 2023.
The incidence rates of PAS diagnoses were 26.5 per 100 person-months among COVID-19 patients within 31-90 days versus 25.9 for influenza patients.
Among inpatient settings, COVID-19 patients had an adjusted hazard ratio of 1.31 for developing severe PAS conditions within 31-90 days after infection.
Article: Charting the Circulating Proteome in ME/CFS: Cross System Profiling and Mechanistic insights | medRxiv
Study Shows Distinct Protein Changes in ME/CFS Patients, Suggesting New Paths for Diagnosis and Treatment
🗞️ Definitions
Immuno Dysregulation: A disruption in normal immune functioning, leading to either underreactivity or overreactivity to antigens.
Metabolomics: The comprehensive analysis of metabolites in a biological sample for insights into physiological states.
🗞️ Summary
The study identifies significant alterations in the circulating proteome of 54 ME/CFS patients compared to 27 healthy controls, with 1823 aptamers showing statistically significant differences.
A pronounced reduction in intracellular proteins, particularly from skeletal muscle, contrasts with a broad increase in secreted proteins linked to immune activity and inflammation.
Key findings highlight immune cell-specific signatures, suggesting immune reprogramming, including decreased neutrophil-associated proteins, indicating potential functional impairments.
The observed serum proteomic patterns could elucidate the multifaceted pathophysiology of ME/CFS and identify novel biomarkers for diagnosis and treatment.
This study emphasizes the importance of investigating circulating proteins to better understand the mechanisms underlying ME/CFS and guide therapeutic strategies.
🗞️ Stats/trends
The study analyzed serum samples from 54 ME/CFS patients and 27 age- and sex-matched healthy controls.
Among the total 7326 aptamers measured, 1823 demonstrated significant differences (p < 0.05), with 845 remaining significant after false discovery rate correction.
Principal Component Analysis indicated partial separation between ME/CFS and control
Article: The Importance of Playing the Long Game With Long COVID and Long-Term Hospital Recovery | Critical Care Medicine | JAMA Network Open
Children in the ICU with MIS-C Face Prolonged Challenges
🗞️ Definitions
Multisystem Inflammatory Syndrome in Children (MIS-C): A severe condition associated with COVID-19 characterized by inflammation in multiple organ systems, primarily affecting children and adolescents.
Neurocognitive Sequelae: Long-term neurological and cognitive complications that can persist following severe infections like COVID-19.
🗞️ Summary
The study by Rollins et al. reveals that many children hospitalized with MIS-C continue to show improvement in neurocognitive outcomes beyond 12 months post-discharge, with significant recovery observed by the 24-month mark.
A noteworthy finding is that pediatric patients who were admitted to the ICU exhibited ongoing executive function challenges even two years after hospitalization, indicating a potentially prolonged recovery phase associated with more severe illness.
The authors emphasize the necessity of extending follow-up evaluations past one year to capture the true trajectory of recovery, noting that children's brains are still developing and may require additional time to reach peer-level functioning.
Incorporation of data on physical activity levels revealed a positive correlation between increased daily movement and improved symptom outcomes, highlighting the importance of activity in pediatric recovery.
The study underscores the importance of pediatric hospital follow-up programs to monitor and support recovery from long-term neurocognitive and psychological effects post-hospitalization.
🗞️ Stats/trends
The study followed a cohort of 59 children hospitalized with MIS-C and 36 matched controls over two years.
Initial assessments showed persistent neurocognitive issues in many children with MIS-C 12 months after hospitalization, with most improving by 24 months, aligning closely with controls.
Children admitted to the ICU had significantly higher ongoing challenges in executive functioning than those on general wards.
Article: Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome | Clinical and Translational Medicine
Extracellular vesicles profoundly dysregulated in ME/CFS patients
🗞️ Definitions
Extracellular vesicles (EVs): Small, membrane-bound particles released by cells that play critical roles in intercellular communication. Exercise has been shown to increase the release of EVs into circulation.
Endoplasmic Reticulum (ER): A network of membranous tubules within the cell, involved in protein and lipid synthesis.
Tricarboxylic Acid (TCA) cycle: A series of energy-producing biochemical reactions. Also known as the Krebs cycle.
🗞️ Summary
The goal of this study was to comprehensively analyze the proteomic cargo of EVs and investigate alterations in EV signaling isolated from the plasma of 10 male ME/CFS patients and 12 age- and BMI-matched healthy sedentary male controls before, 15 min, and 24 h after a maximal exercise challenge.
After exercise, ME/CFS patients showed profound dysregulation in EV proteomic cargo and other altered EV proteomic responses compared with controls, including downregulation of tricarboxylic acid (TCA) cycle-related proteins and upregulation of complement system proteins.
PEM severity was highly correlated with protein changes involved in protein folding and the endoplasmic reticulum (ER) stress response during recovery, highlighting their potential as therapeutic targets.
EV protein changes postexercise were also associated with disease severity and unrefreshing sleep.
There were correlations between EV protein levels and exercise parameters observed in controls but absent in ME/CFS patients, suggesting disrupted EV-mediated physiological processes.
The response to exercise in male ME/CFS patients’ EV proteome is characterized by an inadequate metabolic and ER stress response combined with heightened immune system activation.
Media
Article: CWCI: Long COVID Accounts for Three Quarters of California Workers’ Comp COVID Claim Payments | Business Wire
🗞️ Summary
Long COVID claims, representing only 4.7% of California workers' comp COVID claims, accounted for 82% of total medical treatment expenditures.
Average medical payments for Long COVID cases were 105 times higher than for shorter duration COVID claims, highlighting the financial burden of this condition.
Of the 126,397 COVID-19 claims reviewed, 14.6% required medical treatment.
Respiratory issues were the most common diagnostic category for Long COVID claims, constituting 17.8% of cases.
Article: ADDRESS-LC Study of Long COVID Initiated, Phase 4 Trial Testing IVIg Transition to Efgartigimod, Lack of Rebound Effect Seen in Ozanimo | Neurology Live
🗞️ Summary
The ADDRESS-LC study has initiated its Phase 4 trial to assess the transition from IVIg to efgartigimod in patients suffering from Llong COVID, highlighting a novel approach in managing this condition.
Efgartigimod: A therapeutic agent designed to reduce pathogenic IgG antibodies, potentially beneficial in autoimmune diseases and long COVID.
Ozanimod: An oral medication acting as a selective sphingosine-1-phosphate receptor modulator, investigated for multiple sclerosis and other conditions, noted for its lack of rebound effect in the latest study.
Preliminary findings reveal no rebound effect associated with ozanimod, addressing previous concerns in its clinical application for neurological disorders.
The presentation of the study structure at the 2025 Peripheral Nerve Society Annual Meeting illustrates an important step in evaluating long COVID treatments through innovative therapeutic approaches.
The research aims to provide insights into the long-term efficacy and safety of efgartigimod in a post-viral context, marking a significant advancement in understanding Long COVID pathophysiology.
Just over five years with debilitating long COVID here, just found your Substack—what an incredible weekly delivery of information, direct to my inbox! Thank you so much for your time and energies on this! ❤️❤️❤️
I did speech therapy (cognitive rehabilitation) with no improvement. It was just kind of distressing in my experience 😣