What's new
New projects, trials due to report, and this year's studies, gathered from across the site.
Projects started (35) · Trials due to report (37) · Trial results published in 2026 (75) · Atlas findings with 2026 studies (99)
Projects started in the last six months
- Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post-Acute Sequelae of SARS-CoV-2 (PD1-PASC I)2026-11-02 · long COVID · National Institute of Neurological Disorders and Stroke (NINDS), USA
- Low-dose Naltrexone (LDN) for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Dose-Finding2026-11-01 · ME/CFS · University of Alabama at Birmingham, USA
- Fatigue in Long COVID Managed With Conservative Care: An International, Randomized Controlled Trial (FALCON Trial)2026-11 · long COVID · McMaster University
- SARS-CoV-2 and Herpesvirus Inhibition for Ending Long COVID Dysfunction (SHIELD)2026-10-20 · long COVID · Icahn School of Medicine at Mount Sinai, USA
- Multicentre study of the effectiveness of multimodal coaching interventions and the feasibility of point-of-care test device for improving the quality of life, functional capacity, and self-management in patients with myalgic encephalomyelitis/chronic fatigue syndrome2026-10-15 · ME/CFS · Canada; France
- Prospective, Randomized, Double-blind, Placebo-controlled Phase 2a Trial of Low-dose Aripiprazole in Patients With Neuropsychiatric Impairment in Post-acute Infectious Syndrome (PAIS) Including Post-COVID-19 Condition (PCC)2026-10-01 · long COVID · Christiana Franke, Germany
- Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study2026-10 · both · Oxford Brookes University, UK
- A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of VYD2311 for the Treatment of Adults With Long-COVID or Post-Vaccination Syndrome (FLINTLOCK)2026-10 · long COVID · Invivyd, Inc.
- The Central Role of mTOR in ME/CFS Pathogenesis.2026-09-25 · ME/CFS · Simmaron Research Inc, USA
- Spatial Metabolomic Mapping of Long COVID Tissues Using MALDI Mass Spectrometry Imaging2026-09-20 · long COVID ·
- The Impact of Transcranial Direct Current Stimulation on Quality of Life, Brain Fog, and Fatigue in Patients With Long COVID: Study Protocol of the NEUROSTIM-LC Study2026-09-15 · long COVID · University of Las Palmas de Gran Canaria
- Neuro-PASC (Brain Fog and Fatigue) is Caused by a Dysbiotic Gut Microbiome2026-09-11 · long COVID · University Of Texas Med Br Galveston, USA
- Observational Study With CICR-NAM as a Food for Special Medicinal Purposes in Post-COVID Syndrome (PCS)2026-09-06 · long COVID · University Hospital Schleswig-Holstein
- Dapagliflozin for Long COVID Syndrome2026-09-01 · long COVID · Ottawa Heart Institute Research Corporation, Canada
- Randomized Controlled Trial of Moderate Dose Hydrogen Water as a Treatment for ME/CFS2026-08-15 · ME/CFS · Fred Friedberg, USA
- Micro-choice-based Intervention for Multicausal Fatigue: Proof of Concept Study2026-08-13 · long COVID · University Hospital, Basel, Switzerland, Switzerland
- Identifying Biological Signatures for Long COVID Development in Saliva2026-08-01 · long COVID · Univ Of North Carolina Chapel Hill, USA
- A Pilot Study of Whole Body Hyperthermia for Long Covid or Post-Acute Sequelae of COVID-19 (PASC)2026-08-01 · long COVID · Massachusetts General Hospital, USA
- Early antiviral treatment to prevent viral persistence and inflammation as drivers of Long COVID: a proof-of-concept mechanistic trial2026-07-21 · long COVID · University Of California, San Francisco, USA
- Hyperbaric Oxygen Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - A Prospective, Randomized, Double-Blind, Sham-Controlled Study2026-07-19 · ME/CFS · Assaf-Harofeh Medical Center, Israel
- Randomized Controlled Trial to Assess the Efficacy of a Supervised Computerized Active Program (SuperCAP) to Improve Cognition and Daily Functioning in People With Post-COVID-19 Condition2026-07-15 · long COVID · Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia, Spain
- A Multi-Center, Individually-Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Superiority Trial to Evaluate the Efficacy of the Combination of Maraviroc and Atorvastatin for the Treatment of Subjects With Long COVID2026-07-15 · long COVID · HealthBio, Inc., USA
- Randomized adaptive assessment of post COVID syndrome treatments (RAPID): Evaluating the Efficacy of Bupropion for the Treatment of Post-COVID-19 Syndrome-associated Fatigue (ELAPSE)2026-07-15 · long COVID · Goethe University Frankfurt, Germany
- A Pilot Randomized Controlled Trial of Homeopathic Treatment for Long COVID2026-07-15 · long COVID · St. Mary's University, Twickenham, UK
- Identification of molecular-neuropathological signatures in AD, FTLD and Long COVID2026-07-01 · long COVID · University Of California Los Angeles, USA
- DISCOVER-ME: Biological evidence and mechanism-based disease classification for the improved diagnosis, prognosis and treatment of ME/CFS (DISCOVER-ME)2026-07-01 · ME/CFS · Medizinische Universitaet Wien, Austria
- Brain Training for Chronic, Post-viral, Brain Fog: Study A2026-06-23 · both · University of Alabama at Birmingham, USA
- The Role of Photobiomodulation in Patients With Chronic Fatigue Syndrome2026-06-15 · ME/CFS · University of Lahore, Pakistan
- sElective Serotonin reuPtake inhibitoRs In posT-covid: ESPRIT2026-06-04 · long COVID · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Netherlands
- Urinary Extracellular Vesicle Profiling to Identify Borrelia-Associated Neuroimmune Subtypes in Long COVID2026-06-03 · long COVID ·
- Infection-Triggered Neurodegeneration in Long COVID: Retinal Biomarkers and Organoid Models for Mechanism and Therapy2026-06-03 · long COVID ·
- REenergizeME: Oxygen Therapy (OT) as a Novel Treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)2026-06-01 · ME/CFS · University of Aarhus, Denmark
- Phase II, Proof of Concept, Open-Label, Randomized-Controlled Trial Evaluating the Efficacy and Safety of PARAGON Novel Metabolic Regulator Formula (PNMR) in the Management of Long COVID2026-05-20 · long COVID · ParagonClinicals Inc., Canada
- A Randomized Controlled Trial for Cervicothoracic Sympathetic Chain Block Against Placebo Saline Injection Evaluation for Post COVID Condition: the CeASE RCT2026-05-19 · long COVID · University Health Network, Toronto, Canada
- Stratification of ME/CFS by mycotoxin exposure2026-05-08 · ME/CFS · Nova Southeastern University, USA
Trials due to finish in the next six months
Results to watch for. Dates are the registered primary completion and often slip.
- tenofovir/emtricitabine long COVID · n=90 · RCT-placebo · due 2026-11
- COCO-Long'Run long COVID · n=200 · RCT-usual-care · due 2026-11
- CBT/psychological therapy long COVID · n=100 · RCT-usual-care · due 2026-11
- REVERSE-LC long COVID · n=550 · RCT-placebo · due 2026-11
- anticoagulant/antiplatelet both · n=120 · open-label · due 2026-12
- exercise/rehabilitation + vagus nerve stimulation long COVID · n=30 · RCT-active · due 2026-12
- CBT/psychological therapy + cognitive rehabilitation long COVID · n=10 · single-arm · due 2026-12
- exercise/rehabilitation long COVID · n=45 · crossover · due 2026-12
- percutaneous electrical nerve-field stimulation, PENFS; percutaneous electrical nerve-field stimulation, PENFS (sham device) long COVID · n=125 · RCT-placebo · due 2026-12
- LOCITT long COVID · n=1000 · RCT-placebo · due 2026-12
- (deu)pirfenidone + JAK inhibitor long COVID · n=348 · RCT-placebo · due 2026-12
- COVID-19 long COVID · n=104 · RCT-placebo · due 2026-12
- IMPACT-LC long COVID · n=252 · RCT-placebo · due 2026-12
- photobiomodulation ME/CFS · n=40 · RCT-placebo · due 2026-12
- immunoglobulin (IVIG/SCIG) long COVID · n=45 · RCT-placebo · due 2026-12
- exercise/rehabilitation both · n=147 · RCT-usual-care · due 2026-12
- vagus nerve stimulation both · n=50 · RCT-active · due 2026-12
- exercise/rehabilitation long COVID · n=50 · RCT-usual-care · due 2026-12
- cognitive rehabilitation long COVID · n=374 · RCT-active · due 2026-12
- rapamycin (sirolimus) long COVID · n=80 · RCT-placebo · due 2026-12
- ACUCM-LC long COVID · n=10 · single-arm · due 2026-12
- ME/CFS both · n=50 · crossover · due 2027-01
- transcranial stimulation/neurofeedback long COVID · n=102 · RCT-placebo · due 2027-01
- AFTERMATH long COVID · n=520 · RCT-usual-care · due 2027-01
- CBT/psychological therapy ME/CFS · n=100 · RCT-usual-care · due 2027-01
- Cryotherapy both · n=40 · single-arm · due 2027-01
- BOOST long COVID · n=80 · single-arm · due 2027-01
- HydroCoVital A long COVID · n=50 · RCT-active · due 2027-01
- HydroCoVitalB long COVID · n=30 · RCT-usual-care · due 2027-01
- STAR-CO long COVID · n=40 · RCT-placebo · due 2027-02
- SON4PEM long COVID · n=80 · RCT-placebo · due 2027-02
- exercise/rehabilitation ME/CFS · n=75 · RCT-active · due 2027-02
- N-803 (IL-15 superagonist) long COVID · n=40 · single-arm · due 2027-03
- CBT/psychological therapy long COVID · n=400 · RCT-usual-care · due 2027-04
- NAC ME/CFS ME/CFS · n=95 · RCT-placebo · due 2027-04
- COVMENT long COVID · n=140 · RCT-placebo · due 2027-04
- vagus nerve stimulation long COVID · n=120 · crossover · due 2027-05
Trial results published in 2026
- Insights from a double-blind, randomized, direct-to-participant intervention trial for Long COVIDinjectable repurposed drug (decentralised trial) · long COVID · result: not-assessable
- Nirmatrelvir-ritonavir targeting viral persistence in post-COVID-19 condition (long COVID) in the USA (RECOVER-VITAL): a randomised, double-blind, placebo-controlled, phase 2 trial.RECOVER-VITAL · long COVID · result: null
- The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID : An Adaptive Randomized Trial.REVIVE · both · result: mixed
- Neither Metformin nor Ursodeoxycholic Acid Effectively Treats Postacute Sequelae of COVID-19 : A Randomized Clinical Trial.metformin / ursodeoxycholic acid · long COVID · result: null
- Evaluation of Interventions for Cognitive Symptoms in Long COVID: A Randomized Clinical Trial.cognitive rehabilitation + transcranial stimulation/neurofeedback · long COVID · result: null
- [Compound Ciwujia Granules for chronic fatigue syndrome with syndrome of deficiency of both heart and spleen: a multicenter, randomized, double-blind, double-dummy, positive drug-controlled trial].herbal/TCM · ME/CFS · result: positive
- Temelimab versus placebo in patients with post-COVID condition.temelimab · long COVID · result: null
- Evaluation of an integrated multidisciplinary care model for myalgic encephalomyelitis/chronic fatigue syndrome: A prospective, open-label, non-randomized controlled intervention study.integrated multidisciplinary care · ME/CFS · result: null
- Low Dose Naltrexone for Post-COVID Fatigue Syndrome: A Randomized Controlled Triallow-dose naltrexone · both · result: null
- Tele-rehabilitation for individuals with long COVID: a randomised clinical trial.virtual rehabilitation (exercise) · long COVID · result: mixed
- Symptom-based rehabilitation in people with post-COVID-19 condition (RELOAD study): a randomised controlled trial.RELOAD · long COVID · result: positive
- Testing the Feasibility of a Self-Help Intervention That Includes Lymphatic Drainage to Reduce Fatigue-Related Symptoms Among Patients with Long COVID in General Practice: Experiences from Our Randomized Controlled Trial (RCT).self-help lymphatic drainage · long COVID · result: feasibility-only
- Treatment effects of multimodal inpatient psychotherapy for post-COVID patients: First results from a non-randomized, controlled study.multimodal inpatient psychotherapy · long COVID · result: mixed
- Effectiveness of an Exercise-Based Telerehabilitation on Cardiorespiratory Fitness, Gait Speed, and Symptoms in Individuals with Long COVID: A Randomized Controlled TrialKNEESUP smart knee assistive device + KNEESUP care APP; Healthy consulation · long COVID · result: positive
- Impact of Pulmonary Rehabilitation on Physical, Mental Health and Quality of Life in Children with Post-COVID-19 Condition: A 12-Month Quasi-Experimental Study.multidisciplinary rehabilitation · long COVID · result: positive
- Effect of Percutaneous Auricular Nerve Stimulation on Fatigue in Adults with Post-COVID Fatigue (PAuSing-pCF): Results of a Randomised, Sham-Controlled Trialauricular vagus nerve stimulation · long COVID · result: null
- Digital rehabilitation using immersive Virtual Reality for Post-COVID fatigue: a double-blind randomized controlled trial.immersive VR + exercise/rehabilitation · long COVID · result: null
- Herbal medicine (Kyungok-go) for fatigue in Long COVID patients: A prospective multicenter pilot study.Kyungok-go (Korean herbal) · long COVID · result: positive
- Cognitive Rehabilitation and Functional Outcomes in Long COVID-Related Cognitive Impairment: A Randomized Clinical Trial.cognitive rehabilitation · long COVID · result: positive
- An open-label feasibility study of remdesivir in long COVID: results from the ERASE LC trial.ERASE-LC · long COVID · result: feasibility-only
- An open-label, clinical feasibility study of the efficacy of Remdesivir for Long-COVID.ERASE-LC · long COVID · result: feasibility-only
- Preliminary evaluation of a cognitive rehabilitation intervention for post-COVID-19 cognitive impairment: A pilot randomized controlled trial.cognitive rehabilitation · long COVID · result: mixed
- Resting-State Functional Connectivity and Cognitive Performance in Long COVID: A Randomized Controlled Trialcognitive rehabilitation · long COVID · result: mixed
- Creatine supplementation on fatigue related to post-COVID-19 condition-fatigue study: a randomized controlled trial.creatine · long COVID · result: positive
- Transcranial direct current stimulation-augmented cognitive training for post-COVID-19 cognition: A phase IIb randomized controlled trialtranscranial stimulation/neurofeedback + cognitive rehabilitation · long COVID · result: mixed
- Evaluation of a multidisciplinary neurological rehabilitation program for the post-COVID-19 condition.multidisciplinary neurological rehabilitation · long COVID · result: mixed
- Effects of Cacao Flavonoids in Long COVID-19 Patients with Chronic Fatigue: FLALOC, a Placebo-Controlled Randomized Clinical Trial.FLALOC · both · result: positive
- Transcutaneous Auricular Vagal Nerve Stimulation Against Fatigue Syndrome in Patients with Long COVID: Results of the Randomized, Placebo-Controlled Clinical Pilot Trial COVIVA.transcutaneous auricular VNS · long COVID · result: null
- Effect of L-Citrulline Supplementation on Endothelial Function and Body Composition in Post-COVID-19 Syndrome: A Randomized Clinical Trial.L-citrulline · long COVID · result: positive
- Immunoadsorption Versus Sham Treatment for Post-COVID Syndrome: A Randomised Sham-Controlled Crossover Trial.IAMPOCO · long COVID · result: null
Atlas findings with 2026 studies
- Replicated On average, people with ME/CFS have mildly lower free cortisol (salivary awakening and morning cortisol, 24-h urinary cortisol and hair cortisol) than healthy controls.Hormones
- Several studies Challenge tests show a blunted cortisol response to ACTH and exaggerated cortisol suppression after a glucocorticoid dose, consistent with enhanced negative feedback.Hormones
- Contested Lower cortisol in long COVID, reported in a 2023 Nature cohort, has not held up in later clinic and cohort studies that controlled for sampling time.Hormones
- Early Women with CFS report more endometriosis, heavy bleeding, pelvic pain, hysterectomy and earlier menopause than controls in US population-based case-control studies.Hormones
- Early ME/CFS genetic risk is enriched in brain tissues and the pituitary, but genetically predicted morning cortisol does not change risk.Hormones
- Replicated The genome-wide DecodeME signal replicates in independent cohorts: genetic correlation 0.65-0.73 with the Million Veteran Program CFS GWAS and 0.80-0.90 with UK Biobank CFS, plus concordant directions for sub-threshold SNPs in FinnGen.Genetics
- Several studies Genome-wide ME/CFS heritability is enriched in brain tissues and neurons (including glutamatergic synapse genes and subcortical/cerebellar neuron types), with no enrichment in blood immune cells.Genetics
- Early A 2026 UK Biobank GWAS with stricter, multi-source case definitions (1,268 cases) reports 7 loci that replicate in disjoint UK Biobank or All of Us cohorts (near BICD1, GRIN2A, CSMD1, RORA, CLYBL), though none replicate in all three.Genetics
- Early MR of DecodeME suggests higher mitochondrial DNA copy number is protective and higher GlycA and mean platelet volume raise risk, while genetically predicted metabolite leads (IPA, kynurenine, ketones, carnitine, bile acids) and vitamin D, BMI and blood pressure are null or unreplicated.Genetics
- Contested Proprietary combinatorial SNP analyses (PrecisionLife) report thousands of multi-SNP signatures in UK Biobank and DecodeME, with top vs bottom decile of signature count giving OR 1.64.Genetics
- Contested TRPM3 ion channel dysfunction in NK cells and TRPM3 SNPs are reported repeatedly by one research group, but the SNP studies are tiny and no TRPM3 association appears in GWAS.Genetics
- Several studies Joint hypermobility and Ehlers-Danlos syndrome are over-represented in ME/CFS (Beighton ≥4 in 60% of children with CFS vs 24% of controls; 50% in a Swedish severe cohort; EDS about 100x expected in Finnish registries).Genetics
- Early The replicated deficit of aromatic lactates (indolelactate, phenyllactate, 4-hydroxyphenyllactate) in ME/CFS blood is not predicted by stool bacteria or bacterial genes, so it is probably host-side or due to absorption, not dysbiosis.Gut and microbiome
- Replicated IBS is about seven times more common in ME/CFS (pooled OR 7.20; prevalence about 37%), and IBS status drives much of the measured microbiome difference.Gut and microbiome
- Early ME/CFS genetic risk overlaps with IBS and is enriched in enteric neurons, but genetically predicted gut-derived metabolites (IPA, indolelactate, kynurenine, bile acids) do not change ME/CFS risk.Gut and microbiome
- Early Reduced TRPM3 ion-channel current and calcium influx in patients' NK cells has been reported repeatedly, including a two-site study (36 vs 42), but only ever by one research group.Immune system
- Refuted Elevated IgG against beta2-adrenergic and M3/M4 muscarinic receptors, reported in about 30% of patients by ELISA, is not reproduced by unbiased high-throughput antigen profiling.Immune system
- Refuted Removing autoantibodies by immunoadsorption helps in open-label cohorts but fails against sham control, and antibody removal does not predict who improves.Immune system
- Several studies IgG from long COVID patients transfers pain, fatigue-like behaviour and small-fibre nerve damage to mice in three independent 2026 studies; no equivalent published ME/CFS transfer experiment exists.Immune system
- Early Purified IgG from ME/CFS patients fragments mitochondria and shifts energetics in human endothelial cells, an effect absent with multiple-sclerosis and healthy IgG and lost on Fab/Fc cleavage.Immune system
- Several studies Long COVID immune profiling finds exhausted T cells, myeloid shifts, raised antibodies to non-SARS-CoV-2 viruses especially EBV, and low cortisol, giving a reference phenotype for post-infectious illness.Immune system
- Early Newly reported elevations of serum IL-11 and MMP-9 in female ME/CFS patients are unreplicated single-cohort findings.Immune system
- Early Plasma galectin-9 and artemin are elevated in long COVID and proposed as biomarkers, with links to cognitive symptoms; data mostly from one group.Immune system
- Replicated After infectious mononucleosis in adolescents, 13%, 7% and 4% met paediatric CFS criteria at 6, 12 and 24 months; all 13 cases still ill at 24 months were female.Infection and viruses
- Replicated In RECOVER-Adult, new ME/CFS (IOM criteria) developed at 2.66 per 100 person-years after SARS-CoV-2 infection vs 0.93 in uninfected participants (HR 4.93), and 4.5% of infected participants met criteria.Infection and viruses
- Early Charité studies report a deficient EBV-specific memory B- and T-cell response in CFS (absent or low EBNA-1/VCA antibody-secreting memory B cells in up to 76% of patients, fewer polyfunctional EBNA-1-specific T cells), while CMV responses were normal.Infection and viruses
- Early Genetic instruments for higher EBV DNA load in blood (Kamitaki 2026) are associated with ME/CFS risk in the Million Veteran Program (OR 1.59, p=0.012) but not significantly in DecodeME (OR 1.13, p=0.25).Infection and viruses
- Early Antibodies against herpesvirus dUTPases (EBV, HHV-6, VZV), proposed as a marker of lytic or abortive-lytic reactivation, are higher in ME/CFS in studies from one lab, including a 2026 longitudinal study (873 serum samples, 40 patients vs 16 controls) where levels tracked fatigue severity.Infection and viruses
- Contested Enteroviral VP1 protein was found in stomach biopsies from 82% of 165 CFS patients vs 20% of controls, with EV RNA in 37% vs 5%, but this has not been independently replicated with blinded methods.Infection and viruses
- Several studies SARS-CoV-2 spike, S1 or nucleocapsid antigen is detectable in plasma more often after COVID than in pre-pandemic samples (excess +11% at 3-6 months, +5.4% at 10-14 months), with more antigenemia after more severe acute illness.Infection and viruses
- Refuted Three randomised placebo-controlled trials of 15-25 days of nirmatrelvir-ritonavir in established long COVID (STOP-PASC n=155, PAX LC n=100, RECOVER-VITAL n=959; about 1,214 people in total) found no benefit on primary or secondary outcomes.Infection and viruses
- Early Treating acute COVID-19 with nirmatrelvir may reduce later long COVID: a small terminated Norwegian RCT found 26% vs 43% at 3 months (RR 0.60), echoing observational VA data, but larger prospective evidence is lacking.Infection and viruses
- Refuted Temelimab, an antibody against HERV-W envelope protein, did not reduce fatigue versus placebo in a 203-person RCT of HERV-W-positive post-COVID patients.Infection and viruses
- Early Unbiased blood virome/EV sequencing does not find more viruses in ME/CFS; a TTMV subgroup signal is unreplicated.Infection and viruses
- Replicated On a single maximal exercise test, ME/CFS patients have lower peak oxygen uptake (pooled about 5 ml/kg/min below controls) with a low peak heart rate (chronotropic incompetence).Muscle, exertion and energy
- Contested ME/CFS patients perform worse on a second maximal exercise test 24 h after the first, most clearly in workload and VO2 at the ventilatory threshold, but two independent groups (Lien 2019; Mancini and Natelson 2026) did not reproduce the VO2 effect.Muscle, exertion and energy
- Early ME/CFS muscle has a lower proportion of type I (oxidative) fibres, type I-specific atrophy, lower mitochondrial capacity and fewer capillaries per fibre, a pattern that 60 days of strict bed rest in healthy people did not reproduce.Muscle, exertion and energy
- Refuted The claim that ME/CFS serum changes healthy myoblast mitochondrial respiration failed a pre-registered replication of 67 patients vs 53 controls, though a small 3D engineered-muscle study reported weaker contraction with patient serum.Muscle, exertion and energy
- Several studies Repeated maximal handgrip testing shows lower strength, faster decline across repetitions and poorer recovery after 60 minutes in ME/CFS, correlating with severity and PEM.Muscle, exertion and energy
- Several studies Several designs (aerobic-capacity-matched controls, idiopathic-fatigue and MS comparison groups, and a 60-day bed-rest model) indicate that deconditioning alone does not explain the exercise and muscle abnormalities in ME/CFS.Muscle, exertion and energy
- Several studies People with long COVID have lower peak VO2 than recovered controls on average (about 5 ml/kg/min), with patterns pointing to deconditioning, chronotropic incompetence and impaired peripheral extraction rather than a cardiac or ventilatory limit.Muscle, exertion and energy
- Several studies Invasive CPET in long COVID with exercise intolerance repeatedly shows low systemic oxygen extraction with normal or high cardiac output, and in a subset reduced biventricular filling (preload failure), mirroring ME/CFS iCPET findings.Muscle, exertion and energy
- Several studies Muscle oxidative capacity measured by 31P-MRS (slower PCr recovery) or NIRS is reduced in long COVID, though the deficit does not consistently correlate with fatigue.Muscle, exertion and energy
- Contested Whether standardised exercise provokes measurable post-exertional symptom worsening in long COVID is contested: a crossover RCT found no greater 48-h fatigue than controls, while symptom-tracking studies find variable PESE peaking within 72 h in subsets.Muscle, exertion and energy
- Replicated Blood flow to the brain falls much more than normal during head-up tilt in ME/CFS (about 26% vs 7% in controls), including in patients whose heart rate and blood pressure stay normal.Nervous system and brain
- Replicated Many patients over-breathe when upright and lower their end-tidal CO2. This drives part of the fall in brain blood flow, and correcting it with phenylephrine restored blood flow and working memory in one small trial.Nervous system and brain
- Contested POTS occurs in a minority of ME/CFS patients, and published rates vary widely (about 6-43%) with the setting, the age group and the test protocol.Nervous system and brain
- Several studies On the 10-minute NASA lean test, a subgroup of recent-onset patients shows a rising heart rate with an abnormally narrow pulse pressure. Autonomic specialists say the test has not been validated against tilt or active stand.Nervous system and brain
- Contested Skin biopsies show reduced small-nerve-fibre density in about 31-53% of ME/CFS patients from specialist referral cohorts, but the controlled NIH study found no difference from healthy volunteers.Nervous system and brain
- Several studies Long COVID patients referred for neuropathy evaluation often have small-fibre neuropathy on skin biopsy, including loss of autonomic fibres to sweat glands and hair muscles.Nervous system and brain
- Contested Conventional structural MRI (grey matter volume, routine clinical reads) shows no consistent abnormality in ME/CFS. Reported regional volume differences rarely replicate across groups.Nervous system and brain
- Early Advanced diffusion MRI models report widespread white-matter differences in ME/CFS that conventional DTI misses, and the pattern may differ between post-infectious and gradual-onset cases.Nervous system and brain
- Several studies Brainstem differences (volume larger or smaller, altered signal or connectivity) are among the more often repeated imaging findings in ME/CFS, though the methods differ between studies.Nervous system and brain
- Early During a sustained grip task, ME/CFS patients fatigue earlier while their brain motor-network activity fails to ramp up as it does in controls (NIH; reduced temporoparietal-junction activation).Nervous system and brain
- Several studies Brain lactate measured by MR spectroscopy is raised in ME/CFS: ventricular CSF lactate in three cohorts from one group, and thalamic or regional lactate in two other groups. It is also raised in depression, so it is not specific.Nervous system and brain
- Contested In long COVID, one [11C]PBR28 PET study found widespread raised TSPO signal that correlated with vascular markers, and a [11C]PK11195 study found no group difference.Nervous system and brain
- Contested Resting (supine) cerebral blood flow by ASL or SPECT is reported as lower in some ME/CFS studies, but the results are inconsistent and often confounded by unmeasured orthostatic intolerance.Nervous system and brain
- Early In the NIH cohort, CSF levels of the catechol metabolites DOPA, DOPAC and DHPG were lower in post-infectious ME/CFS. Noradrenaline and dopamine did not differ.Nervous system and brain
- Contested CSF cytokine and proteome studies report differences (e.g. raised eotaxin/CCL11, distinct immunotypes), but no CSF protein signature has replicated, and ME/CFS and fibromyalgia CSF proteomes were indistinguishable.Nervous system and brain
- Early Uncontrolled clinic series report high rates of craniocervical 'obstruction', low-lying tonsils and signs of raised intracranial pressure in severe ME/CFS, and surgical case reports describe improvement. There are no controlled imaging studies or trials.Nervous system and brain
Open funding calls and deadlines are on the funding page.