Tag: 2025

Pacing with a heart rate monitor for people with myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a feasibility study

Abstract:

Background: People living with ME/CFS and LC frequently live with post-exertional malaise (PEM), which is associated with impairments in aerobic metabolism. They often use pacing with a heart rate monitor (HRM) to minimize time spent above the anaerobic threshold; however, there is limited research on the feasibility and efficacy.

Objective: To establish the acceptability, adherence, outcomes, and adverse events associated with pacing with an HRM for a future definitive study.

Methods: After informed consent and baseline measurements (including 10 min stand test, 5 questionnaires, accelerometry, heart rate variability, and lactate), participants were randomized into a control or intervention group using simple randomization and sealed envelopes. The intervention group used a heart rate monitor with weekly online HRM pacing advice (how to use the HRM, problem solving), and the control group received weekly online pacing advice (how to pace, problem solving). Follow-up measures were repeated, and semi-structured interviews were conducted at two and six months post-enrolment.

Results: 47 participants were recruited; however, recruiting people with LC was difficult due to wanting to use/already using HR monitoring. The interviews identified that the procedure was acceptable, and the majority of the participants completed the outcome measures. There were some changes from baseline to follow-up in all the outcome measures except the 10-minute stand test and accelerometry. There were no serious adverse events. Follow-up interviews identified 89% continued using HRM at 8 weeks and 66% after 6 months.

Conclusions: Studies of HRM are feasible and acceptable for ME/CFS and LC, although recruitment strategies should be reviewed for LC.

Clinical Trial registration number: ISRCTN10554129.

Source: Clague-Baker, N., Davenport, T. E., Wickens, B., Leeming, H., Dickinson, K., McBurney, E., … Hilliard, N. (2025). Pacing with a heart rate monitor for people with myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a feasibility study. Fatigue: Biomedicine, Health & Behavior, 1–23. https://doi.org/10.1080/21641846.2025.2565103 https://www.tandfonline.com/doi/full/10.1080/21641846.2025.2565103#abstract (Full text)

Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition characterized by fatigue, cognitive impairment, and reduced physical function. Oxaloacetate (OAA), a metabolic compound with potential mitochondrial and neuroprotective effects, has shown promise in reducing fatigue symptoms in ME/CFS. However, the interrelationships between fatigue, cognitive performance, and physical activity and their responsiveness to treatment remain poorly understood in ME/CFS.

Methods: This 90-day randomized, double-blind, controlled trial evaluated the effects of 2,000 mg/day OAA or a control of 2,000 mg rice flour in 82 adults with ME/CFS. Self-reported fatigue (Chalder Fatigue Questionnaire), cognitive function (DANA Brain Vital), and upright activity time (UP Time) were assessed at baseline and three follow-up visits. Linear mixed-effects models examined associations between fatigue severity and cognitive/physical function, with treatment group interactions. Responder status at the last visit (Visit 4) was classified based on ≥15% fatigue reduction and/or ≥10% cognitive improvement.

Results: The OAA group showed greater cognitive improvement over time, with a significant between-group difference at Visit 3, 60 days into the trial, (p = 0.034) and trends at other visits. Higher fatigue was significantly associated with reduced cognitive gains in the OAA group (β = −0.34, p < 0.0001), but not in controls. UP Time increased modestly in the OAA group, reaching significance at Visit 2, day 30 (p = 0.044), though fatigue was not a strong predictor of UP Time in either group. At Visit 4, day 90, Global and Fatigue Only Responders were more frequent in the OAA group, while Cognitive Only Responders were more frequent in controls, though group differences did not reach statistical significance (p = 0.10).

Conclusion: OAA supplementation was associated with improved cognitive performance and small improvement in UP Time in ME/CFS participants receiving OAA. Fatigue–cognition coupling was particularly strong in OAA-treated participants, suggesting a potentially targetable phenotype. These findings underscore the importance of multidimensional outcome measures in ME/CFS clinical trials and support the need for more research and trials of metabolic interventions in ME/CFS.

Source: Vernon Suzanne D. , Rond Candace , Sun Yifei , Roundy Shad , Bell Jennifer , Rond Bella , Kaufman David L. , Cash Alan B. , Yellman Brayden , Bateman Lucinda. Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in Neurology, Volume 16 – 2025. DOI=10.3389/fneur.2025.1691147 ISSN=1664-2295 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1691147/full (Full text)

Wearable technology in the management of complex chronic illness: preliminary survey results on self-reported outcomes

Abstract:

Introduction: Complex chronic illnesses like Long Covid (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are marked by fluctuating symptoms, often exacerbated by physical, cognitive, or emotional exertion in a phenomenon known as post-exertional malaise (PEM). Home monitoring technologies offer potential benefits by enabling individuals to track symptoms and biometrics, aiding in disease self-management. However, the general effectiveness of such tools is still unknown.

Methods: A random sample of users of the Visible mobile application (Visible Plus; requires both the armband and paid subscription), aged 18 or older and with self-identified complex chronic illnesses such as LC or ME/CFS, were invited to complete an online survey regarding the impact of the app on their chronic disease self-management. Descriptive statistics related to the responses were analyzed and reported.

Results: The survey was distributed to 2,636 people, with 1,301 participants responding (49.3% response rate). The average age was 46 years. 82% of respondents were female, 8% were male, 8% were non-binary, and 2% preferred not to say or preferred to self-describe. Participants self-identified as having ME/CFS only (n = 534, 42%), LC only (n = 396, 31%), ME/CFS and LC (n = 236, 18%), or another illness (n = 122, 10%). Of the n = 2,636 randomly selected subscribers, the mostly commonly listed “other illnesses” were Postural Orthostatic Tachycardia Syndrome (POTS, 6%), fibromyalgia (5.2%), Ehlers Danlos Syndrome (EDS; 1.7%) and Mast Cell Activation Syndrome (MCAS, 1.2%). Of those with at least 30 days of data, 77% reported seeing an improvements associated with app use, corresponding to 23% of all invited users, 85% (corresponding to 29% of all invited users) reported feeling somewhat (53%) or significantly (32%), and 94% (corresponding to 33% of all invited users) reported a better understanding of their energy budget.

Discussion: Home-monitoring based mobile applications are feasible and acceptable for a motivated subgroup of people with energy-limiting complex chronic illnesses, and are associated with self-reported benefits in energy management and participation in daily activities. The findings of this study should be interpreted as descriptive and hypothesis-generating and do not represent clinically significant effects, underscoring the need for randomized controlled trials to formally evaluate efficacy. Future studies should incorporate a comparison group to better differentiate intervention effects from improvements gained through lived experience.

Source: Sawyer Abbey , Preston Rory , Leeming Harry , Martin-Fuller Luke , Proal Amy , Putrino David. Wearable technology in the management of complex chronic illness: preliminary survey results on self-reported outcomes. Frontiers in Digital Health, Volume 7 – 2025. DOI=10.3389/fdgth.2025.1662255. ISSN=2673-253X https://www.frontiersin.org/journals/digital-health/articles/10.3389/fdgth.2025.1662255/full (Full text)

Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrom

Abstract:

Introduction: Epstein-Barr virus (EBV) infection is a well-established trigger and risk factor for both myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID syndrome (PCS). In previous studies, we identified elevated IgG responses to arginine-rich (poly-R) sequences within the EBV nuclear antigens EBNA4 and EBNA6 in post-infectious ME/CFS (piME/CFS). Building on these findings, this exploratory study examines IgG reactivity to poly-R-containing EBV-derived peptides and homologous human peptides in women with PCS and ME/CFS.

Methods: IgG reactivity to poly-R containing peptides derived from EBNA4 and EBNA6, and homologous human 15-mer peptides and the corresponding full-length proteins, was assessed using a cytometric bead array (CBA) and a multiplex dot-blot assay. Serum samples were analyzed from 45 female PCS patients diagnosed according to WHO criteria, including 26 who also met the Canadian Consensus criteria for ME/CFS (pcME/CFS), 36 female patients with non-COVID post-infectious ME/CFS (piME/CFS), and 34 female healthy controls (HC).

Results: Autoantibodies targeting poly-R peptide sequences of the neuronal antigen SRRM3, the ion channel SLC24A3, TGF-β signaling regulator TSPLY2, and the angiogenesis-related protein TSPYL5, as well as full-length α-adrenergic receptor (ADRA) proteins, were more frequently detected in patient groups. Several of these autoantibodies showed positive correlations with core symptoms, including autonomic dysfunction, fatigue, cognitive impairment, and pain.

Conclusion: This exploratory study identify autoantibodies directed against EBV mimicking arginine-rich sequences in human proteins, suggesting a potential role for molecular mimicry in the pathogenesis of PCS and ME/CFS.

Source: Hoheisel Friederike , Fleischer Kathrin Maria , Rubarth Kerstin , Sepúlveda Nuno , Bauer Sandra , Konietschke Frank , Kedor Peters Claudia , Stein Annika Elisa , Wittke Kirsten , Seifert Martina , Bellmann-Strobl Judith , Mautner Josef , Behrends Uta , Scheibenbogen Carmen , Sotzny Franziska. Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in Immunology, Volume 16 – 2025. DOI=10.3389/fimmu.2025.1650948 ISSN=1664-3224 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1650948/full (Full text)

Impacts of long COVID on disability, function and quality of life for adults living in Australia

Abstract:

Background: To describe the impact of long COVID on disability, function and quality of life among adults living in Australia.

Method: People aged >18years with a history of COVID-19 infection confirmed by polymerase chain reaction or rapid antigen test were eligible for this cross-sectional survey. The World Health Organization Disability Assessment Schedule 2.0 measured disability and function, and the 36-Item Short Form Health Survey assessed quality of life.

Results: Participants (n =121) reported significant functional impairment and reduced quality of life compared with established population norms for these outcome measures. Most (n =104, 86%) reported clinically significant disability and participation limitations in daily activities. Mean World Health Organization Disability Assessment Schedule 2.0 scores indicated higher levels of disability than 98% of the general population. The 36-Item Short Form Health Survey scores indicated lower quality of life across all domains, but particularly in relation to vitality and social functioning. Regression analysis found significant associations between the World Health Organization Disability Assessment Schedule 2.0 and 36-Item Short Form Health Survey scores, and vaccine dose number, comorbidities and self-rated recovery.

Conclusion: Long COVID is associated with significantly reduced function and quality of life, which are distinct outcomes requiring targeted assessment and intervention. The overall impact may be exacerbated in people with pre-existing comorbidities who are more susceptible to long COVID in the first place. The findings underscore the need for targeted rehabilitation and support services for people living in Australia with long COVID, and further longitudinal research to explore the long-term impact on disability and quality of life, and inform policy and healthcare service delivery.

Source: Hitch D, Botha T, Tesfay F, Holton S, Said CM, Hensher M, Richards K, Angeles MR, Bennett CM, Pepin G, Rasmussen B, Nicola-Richmond K. Impacts of long COVID on disability, function and quality of life for adults living in Australia. Aust J Prim Health. 2025 Aug;31:PY25033. doi: 10.1071/PY25033. PMID: 40977216. https://www.publish.csiro.au/py/Fulltext/PY25033 (Full text)

Telehealth as a care solution for homebound people: systematic review and meta-analysis of healthcare utilization, quality of life, and well-being outcomes

Abstract:

Homebound individuals residing in community settings with severe health conditions and disabilities could arguably benefit from telehealth interventions. However, the effectiveness of telehealth compared to in-person care remains underexplored, considering the diversity of these groups. This systematic review and meta-analysis aimed to evaluate the effectiveness of telehealth in reducing healthcare utilization and improving health-related quality of life (HRQOL) and well-being in homebound populations.

Adhering and expanding on a published protocol, we conducted comprehensive search across multiple databases: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, LILACS, and the Web of Science, with no restrictions on language or publication date, and experimental and quasiexperimental studies considered. Eleven independent reviewers were responsible for study selection, and three for data extraction. The methodological quality of the included studies was assessed using JBI checklists. A meta-analysis was then performed using Stata software, which reported standardized mean differences (SMDs) as the effect measure, with the quality of evidence evaluated using the GRADE approach. From an initial screening of 3289 articles, ten studies met our inclusion criteria, with eight suitable for meta-analysis. These studies encompassed data from 2245 participants.

Our findings revealed that telehealth interventions significantly reduced healthcare utilization (SMD: −0.49; 95% CI: −0.76 to −0.22; p < 0.01, GRADE: low certainty), significantly enhanced HRQOL (SMD: 0.18; 95% CI: 0.01 to 0.35; p = 0.04, GRADE: moderate certainty), and significantly improved well-being (SMD: −0.31; 95% CI: −0.47 to −0.15; p < 0.01, GRADE: moderate certainty) compared to in-person care. Thus, telehealth emerges as a viable alternative to conventional care, significantly reducing healthcare utilization and enhancing both HRQOL and well-being for homebound people.

These findings underscore the potential of telehealth to mitigate healthcare disparities and emphasize the need for accessible, equitable telehealth services codeveloped with end users and relevant stakeholders to save resources and maximize health outcomes for vulnerable populations in community settings.

Source: Pinero de Plaza, Maria Alejandra, Gulyani, Aarti, Bulto, Lemma N., Allande-Cussó, Regina, Pearson, Vincent, Lange, Belinda, Marin, Tania, Gebremichael, Lemlem, Brown, Shannon, Dafny, Hila, Sajeev, Shelda, Bulamu, Norma, Beleigoli, Alline, Nesbitt, Katie, McMillan, Penelope, Clark, Robyn, Tieu, Matthew, Kitson, Alison, Champion, Stephanie, Hines, Sonia, Hendriks, Jeroen M., Telehealth as a Care Solution for Homebound People: Systematic Review and Meta-Analysis of Healthcare Utilization, Quality of Life, and Well-Being Outcomes, Health & Social Care in the Community, 2025, 7224151, 32 pages, 2025. https://doi.org/10.1155/hsc/7224151 https://onlinelibrary.wiley.com/doi/full/10.1155/hsc/7224151 (Full text)

Systemic increase of AMPA receptors associated with cognitive impairment of Long COVID

Abstract:

Long COVID primarily presents with persistent cognitive impairment (Cog-LC), imposing a substantial and lasting global burden. Even after the pandemic, there remains a critical global need for diagnostic and therapeutic strategies targeting Cog-LC. Nevertheless, the underlying neural mechanisms remain poorly understood. Given the central role of synapses in brain function, investigation of synaptic molecular changes may provide vital insights into Cog-LC pathophysiology.

In this study, we used [11C]K-2 PET to characterize the density of AMPA receptors (AMPARs) on the post-synaptic cell surface, which are crucial synaptic components in brain signalling. Statistical parametrical mapping was used to spatially normalize and apply independent t-test for a voxel-based comparison.

We selected patients with Cog-LC (n = 30) based on Repeatable Battery for the Assessment of Neuropsychological Status assessed persistent cognitive impairment and healthy controls (n = 80) with no diagnosed neuropsychiatric disorders. The primary objective was to compare [11C]K-2 standardized uptake value ratio with white matter (SUVRWM) as a reference region between patients with Cog-LC and healthy controls, and to define the regional extent of differences. The secondary objective was to examine associations between [11C]K-2 SUVRWM and plasma concentrations of cytokines or chemokines.

As an exploratory objective, we tested whether [11C]K-2 PET data could distinguish Cog-LC from healthy controls using a partial least squares based classification algorithm. A voxel-based comparison (P < 0.05, T > 1.66, one-tailed, false discovery rate control) and a volume of interests analysis (P < 0.05, Bonferroni multiple comparison) demonstrated that increased index of AMPAR density in large parts of the brains of patients with Cog-LC compared with that in healthy controls.

A voxel-based correlation analysis also showed the brain regions where [11C]K-2 SUVRWM correlated positively with plasma TNFSF12 and negatively with plasma CCL2 concentrations.

A partial least squares model trained on the index of AMPAR density data demonstrated high diagnostic accuracy, achieving 100% sensitivity and 91.2% specificity. [11C]K-2 PET signal represents the index of AMPAR density on the post-synaptic neural cell surface, not on the glial cell surface.

A systemic increase in synaptic AMPARs across the brain may drive abnormal information processing in Cog-LC and, through excessive excitatory signalling, pose a risk of excitotoxic neuronal damage.

We derived the hypothesis that [11C]K-2 PET would be helpful in establishing a diagnostic framework for Cog-LC and that antagonists for cell surface AMPARs, such as perampanel, would be a potential therapeutic target. These hypotheses should be investigated in future large-scale clinical studies.

Source: Fujimoto Y, Abe H, Eiro T, Tsugawa S, Tanaka M, Hatano M, Nakajima W, Ichijo S, Arisawa T, Takada Y, Kimura K, Sano A, Hirahata K, Sasaki N, Kimura Y, Takahashi T. Systemic increase of AMPA receptors associated with cognitive impairment of long COVID. Brain Commun. 2025 Oct 1;7(5):fcaf337. doi: 10.1093/braincomms/fcaf337. PMID: 41036177; PMCID: PMC12483584. https://pmc.ncbi.nlm.nih.gov/articles/PMC12483584/ (Full text)

Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study

Abstract:

Importance: Post-acute sequelae of SARS-CoV-2 infection (PASC) remains a major public health challenge. While previous studies have focused on characterizing PASC and identifying its subphenotypes in children and adolescents following an initial SARS-CoV-2 infection, the risks of PASC with Omicron-variant reinfections remain unclear. Using a real-world data approach, this study investigates the risks of PASC following reinfections during the Omicron phase in the pediatric population.

Objective: To investigate the risks of PASC diagnosis and 24 PASC symptoms and conditions after reinfection of SARS-CoV-2 during Omicron period in the pediatric population.

Design setting and participants: This retrospective cohort study used data from the RECOVER consortium comprising 40 children’s hospitals and health institutions in U.S. between January 2022 and October 2023.

Exposures: A second SARS-CoV-2 infection, confirmed by a positive polymerase-chain-reaction (PCR) or antigen tests, or a diagnose of COVID-19, occurring at least 60 days after the initial infection, compared to the initial infection.

Main outcomes and measures: PASC was identified using two approaches: (1) the ICD-10-CM diagnosis code U09.9 and (2) a symptom-based definition including 24 physician-identified symptoms and conditions. Absolute risks of incident PASC were reported, and relative risks (RRs) were calculated by comparing the second infection episode with the first infection episode groups using a modified Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through exact matching and propensity scoring matching.

Results: A total of 465,717 individuals under 21 years old (mean [SD] age 8.17 [6.58] years; 52% male) were included. Compared to the first infection, a second infection was associated with significantly increased risk of an overall PASC diagnosis (RR, 2.08; 95% confidence interval [CI], 1.68-2.59), and with many specific conditions including: myocarditis (RR, 3.60; 95% CI, 1.46-8.86); changes in taste and smell (RR, 2.83; 95% CI, 1.41-5.67); thrombophlebitis and thromboembolism (RR, 2.28; 95% CI, 1.71-3.04); heart disease (RR, 1.96; 95% CI, 1.69 to 2.28); acute kidney injury (RR, 1.90; 95% CI, 1.38 to 2.61); fluid and electrolyte (RR, 1.89; 95% CI, 1.62 to 2.20); generalized pain (RR, 1.70; 95% CI, 1.48 to ; arrhythmias (RR, 1.59; 95% CI, 1.45-1.74); abnormal liver enzyme (RR, 1.56; 95% CI, 1.24 to ; fatigue and malaise (RR, 1.50; 95% CI, 1.38 to 1.64); musculoskeletal pain (RR, 1.45; 95% CI, 1.37 to 1.54); abdominal pain (RR, 1.42; 95% CI, 1.34 to 1.50); postural orthostatic tachycardia syndromes (POTS)/dysautonomia (RR, 1.35; 95% CI, 1.20 to 1.51); cognitive functions (RR, 1.32; 95% CI, 1.15 to 1.50); and respiratory signs and symptoms (RR, 1.29; 95% CI, 1.25 to 1.33). The risks were consistent across various organ systems, including cardiovascular, respiratory, gastrointestinal, neurological, and musculoskeletal systems.

Conclusions and relevance: Children and adolescents face significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings suggest a cumulative risk of PASC and highlight the urgent need for targeted prevention strategies to reduce reinfections, which includes an increased emphasis on initial or re-vaccination of children.

Source: Zhang B, Wu Q, Jhaveri R, Zhou T, Becich MJ, Bisyuk Y, Blanceró F, Chrischilles EA, Chuang CH, Cowell LG, Fort D, Horowitz CR, Kim S, Ladino N, Liebovitz DM, Liu M, Mosa ASM, Schwenk HT, Suresh S, Taylor BW, Williams DA, Morris JS, Forrest CB, Chen Y. Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study. medRxiv [Preprint]. 2025 Mar 30:2025.03.28.25324858. doi: 10.1101/2025.03.28.25324858. PMID: 40196285; PMCID: PMC11974971. https://pmc.ncbi.nlm.nih.gov/articles/PMC11974971/ (Full text)

Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study

Summary:

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge. Although previous studies have focused on characterising PASC in children and adolescents after an initial infection, the risks of PASC after reinfection with the omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period.

Methods: This retrospective cohort study used data from 40 children’s hospitals and health institutions in the USA participating in the Researching COVID to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen tests, or a diagnosis of COVID-19 that occurred at least 60 days after the first infection. The primary endpoint was a clinician-documented diagnosis of PASC (U09.9). Secondary endpoints were 24 symptoms and conditions previously identified as being potentially related to PASC. We used the modified Poisson regression model to estimate the relative risk (RR) between the second and first infection episodes, adjusted for demographic, clinical, and health-care utilisation factors using exact and propensity-score matching.

Findings: We identified 407 300 (87·5%) of 465 717 eligible children and adolescents with a first infection episode and 58 417 (12·5%) with a second infection episode from Jan 1, 2022, to Oct 13, 2023, in the RECOVER database. 233 842 (50·2%) patients were male and 231 875 (49·8%) were female. The mean age was 8·17 years (SD 6·58). The incident rate of PASC diagnosis (U09.9) per million people per 6 months was 903·7 (95% CI 780·9–1026·5) in the first infection group and 1883·7 (1565·1–2202·3) in the second infection group. Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (U09.9) (RR 2·08 [1·68–2·59]) and a range of symptoms and conditions potentially related to PASC (RR range 1·15–3·60), including myocarditis, changes in taste and smell, thrombophlebitis and thromboembolism, heart disease, acute kidney injury, fluid and electrolyte disturbance, generalised pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, POTS or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory signs and symptoms, and cardiovascular signs and symptoms.

Interpretation: Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long COVID to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies.

Funding: National Institutes of Health.

Source: Zhang, Bingyu et al. Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study. The Lancet Infectious Diseases, Volume 0, Issue 0, Online first; September 30, 2025. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00476-1/fulltext (Full text)