The protein WASF3, which is elevated in ME/CFS, blocks respiratory complex IV in mitochondria and shifts energy metabolism in the hippocampus toward glycolysis – a 'hypometabolic' state. Mice with elevated WASF3 showed learning deficits and reduced ATPIF1 levels, while WASF3-deficient mice preserved cognitive function even under stress. These findings provide a concrete molecular mechanism for cognitive impairment in ME/CFS.

This study provides, for the first time, a clear molecular mechanism for 'brain fog' in ME/CFS and directly links mitochondrial dysfunction to cognitive symptoms. WASF3 could become a new target for diagnostics and therapy.

This systematic review of 22 studies compared persistent symptoms after SARS-CoV-2 with those following other respiratory viruses. Increased risks after COVID-19 were observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations. However, most other outcomes occurred at similar rates after other viral infections.

The study scientifically confirms that post-viral syndromes like ME/CFS and PVFS are a broader phenomenon that also occurs after other infections. This supports the call for recognized diagnostics and treatment of these conditions regardless of the triggering pathogen and suggests shared mechanisms.

In a study with 20 Long COVID patients (with fatigue, brain fog, and PEM) and 20 controls, EEG revealed a reduced post-movement beta rebound (PMBR) during handgrips and a slower alpha central frequency at rest. These EEG markers correlated with cognitive symptoms and fatigue severity, suggesting impaired inhibitory control and reduced excitability in the sensorimotor cortex.

The study identifies potential objective EEG biomarkers for the typical Long COVID symptoms of fatigue and brain fog, which are also central complaints in ME/CFS. Objective biomarkers are urgently needed for diagnosis and understanding of these conditions.

The study analyzed 155 participants in four groups and found persistent systemic inflammation and altered IgA/IgG levels in Long COVID patients. In the group with memory and reasoning problems, a positive correlation between TNF-α and Tau protein was observed. This suggests chronic inflammatory processes contribute to cognitive symptoms, even without strong evidence of direct neuronal damage.

Cognitive symptoms ('brain fog') and chronic inflammation are core symptoms in ME/CFS and Long COVID. The identified biomarkers could serve as objective diagnostic markers and provide clues for treatment approaches targeting neuroinflammation.

The study followed 29 patients with neurological Long COVID (headache, fatigue, sleep disturbance, cognitive complaints) over one year. GFAP (glial activation marker) remained elevated long-term, NfL rose acutely, and complement activation (C5b-9) remained persistently increased. Patients also showed a higher cumulative autoantibody burden, suggesting broad nonspecific immune activation as a driver of symptom persistence.

The findings provide potential objective biomarkers (GFAP, C5b-9) and a mechanistic explanation for the neurological complaints in Long COVID that strongly overlap with ME/CFS. The role of complement activation and autoantibodies could open new therapeutic avenues.

In a case-control study of 45 Long COVID patients and 45 controls, saliva was tested for herpesviruses (EBV, HSV, HCMV, HHV-6) and for cortisol, testosterone and oestradiol. No between-group differences in viral DNA or hormone levels were found, but within the Long COVID group higher HHV-6 DNA correlated significantly with greater symptom severity. The authors conclude that HHV-6 may contribute to Long COVID pathophysiology.

Reactivation of herpesviruses like HHV-6 is a central hypothesis in ME/CFS and Long COVID pathogenesis. This study provides an easily accessible (saliva-based) biomarker signal that correlates directly with disease severity and highlights potential targets for antiviral therapy.

In Stem Cell Educator (SCE) therapy, patient immune cells are extracted, 're-educated' in the lab with multipotent cord blood stem cells, and then returned. In a study with 25 Long COVID patients, fatigue and brain fog disappeared in 21 patients, and inflammatory markers such as IL-1β and CXCL16 decreased. The therapy was well tolerated with only mild side effects.

This therapy directly targets the chronic immune dysregulation suspected in Long COVID and ME/CFS. The high response rate and measurable reduction of inflammatory markers make this approach a promising candidate for larger trials, including in ME/CFS patients.

In a study of 34 youth, Long COVID patients showed lower cumulative hair cortisol levels and reduced parasympathetic activity (heart rate variability) compared to those with depressive disorders. Within the Long COVID group, fatigue was linked to attenuated parasympathetic function and lower cortisol. This suggests distinct psychobiological signatures of Long COVID despite symptom overlap with depression.

The study provides objective biological markers that distinguish Long COVID from depression — important as patients are often misdiagnosed as mentally ill. Autonomic dysfunction and HPA axis alterations are also central mechanisms in ME/CFS.

Researchers tested 13 receptor-binding autoantibodies (including against G-protein coupled receptors) in people with and without post-COVID fatigue. No significant differences in antibody concentrations were found between groups, nor in relation to fatigue severity. The authors stress that functional antibody assays and longitudinal studies are still needed.

Autoantibodies against GPCRs (e.g. beta-adrenergic, muscarinic receptors) have long been considered potential biomarkers and disease drivers in ME/CFS and Long COVID. This negative study challenges the diagnostic utility of simple antibody binding assays and urges caution regarding commercial tests, while calling for functional assays to clarify the issue.

This systematic review included 59 cohort studies with at least 12 weeks of follow-up after COVID-19 infection. Fatigue persisted in about 29% of individuals and dyspnea in 16%. Interestingly, healthcare workers showed lower prevalence rates for several symptoms compared to the general population.

The high prevalence of persistent fatigue after COVID-19 highlights the substantial health burden of Long COVID and PVFS/ME-CFS-like conditions and underscores the need for further research on mechanisms and treatments.

The review summarizes evidence for autonomic dysfunction in fibromyalgia, including reduced HRV, altered sympathovagal regulation, orthostatic intolerance and POTS. It discusses links with small fiber neuropathy and central autonomic networks, and emerging treatments such as HRV biofeedback, non-invasive vagal modulation and vestibular rehabilitation. The authors advocate phenotype-based, personalized management.

Fibromyalgia shares key features with ME/CFS such as autonomic dysfunction, POTS, small fiber neuropathy and central sensitization. The described diagnostic and treatment approaches (HRV biofeedback, vagal stimulation, phenotyping) are directly transferable to ME/CFS.

A study of 137 Long COVID patients over 3-24 months found sST2 blood levels were normal and did not differ between patients with or without fatigue, dyspnea, or lung function impairment. There was also no correlation with other vascular damage markers (VEGF-A, VWF, CECs, D-dimers). This suggests other, IL-33/sST2-independent mechanisms drive chronic vascular injury in Long COVID.

The study rules out a promising biomarker for Long COVID and directs research toward alternative mechanisms of persistent vascular damage that may be relevant to fatigue and exertion intolerance.

In a 12-month study of 74 colorectal cancer survivors, diurnal cortisol was measured repeatedly and correlated with fatigue. Higher relative amplitude and steeper diurnal decline were associated with less fatigue. The authors suggest HPA axis dysregulation may contribute to chronic fatigue.

HPA axis dysregulation and flattened cortisol rhythms are also discussed in ME/CFS; findings support the hypothesis that circadian disruption contributes to fatigue.

The study examined deceased COVID-19 patients, long COVID sufferers with symptoms lasting 1-5 years, and a mouse model. In all cases, a markedly increased density of ACE2+ microvasculature was found with persistent spike protein presence and collagen deposition (fibrosis). Results point to a spike-induced chronic restrictive microangiopathy as a potential cause of many long COVID symptoms.

This is a pivotal study for explaining long COVID: it provides direct evidence of viral spike protein persistence over years, endothelial damage, and restricted tissue perfusion - all mechanisms also discussed in ME/CFS. Potential therapeutic approaches could target spike protein removal or microangiopathy treatment.

The study examined 40 adolescents (10-17 years) with ME/CFS: 89% missed school, 64% received homebound/homeschool instruction, and they missed an average of 10.8 school days per month. Core symptoms like PEM, unrefreshing sleep, fatigue and cognitive impairment were common. Compared to 595 adults, adolescents had shorter illness duration and better physical functioning but similar mental health scores.

The study documents the substantial burden on children and adolescents with ME/CFS and highlights the need for early diagnosis and appropriate educational support. It confirms that pediatric ME/CFS shares core symptoms with adult ME/CFS.

The 'Metabolic Debt Model' links four metabolic constraints—phosphocreatine buffering, astrocyte-neuron coupling, mitochondrial flexibility, and NAD+-dependent recovery—to network-level brain dysfunction. These cumulative bioenergetic burdens could explain clinical symptoms in ME/CFS and Long COVID. The model serves as a hypothesis-generating framework for future research.

The model directly addresses ME/CFS and Long COVID, offering an integrative explanation for core symptoms like post-exertional malaise and cognitive dysfunction. It could justify new therapeutic approaches (e.g., NAD+ supplementation, mitochondrial support) and guide biomarker research.

By combining transcriptomic analyses, single-cell sequencing and cell experiments, HMGCR and SGK1 were identified as core genes associated with cellular senescence and inflammation in ME/CFS. SGK1 was particularly elevated in monocytes and neutrophils of ME/CFS patients. In a cell model, SGK1 knockdown reduced typical aging markers (p16, p21, p53).

The study provides a new mechanistic approach to explain immune dysregulation in ME/CFS via premature senescence of myeloid cells. SGK1 could serve as a biomarker and potential therapeutic target – especially since SGK1 inhibitors are already under development.

The study analyzed blood samples from 160 participants and found that senescence-associated genes (SenMayo signature) were significantly upregulated in individuals who later developed Long COVID symptoms including fatigue, cognitive impairment, and exercise intolerance. The gene ETS2 was upregulated across all impairment phenotypes, while other genes showed phenotype-specific patterns. This suggests cellular senescence as a possible pathophysiological mechanism.

Cellular senescence could explain chronic inflammation, immune dysregulation and exercise intolerance in Long COVID and possibly ME/CFS. Senolytics (drugs targeting senescent cells) could represent a novel therapeutic approach and offer a drug repurposing opportunity.

In 153 individuals studied two years after SARS-CoV-2 infection, PEM, ME/CFS symptoms and sleep disturbance showed the strongest association with Long COVID. Cluster analyses revealed two clinically distinct subtypes among those with severe fatigue – one dominated by physical impairment and one by cognitive dysfunction. This heterogeneity may enable future targeted diagnosis and treatment.

The study confirms PEM and ME/CFS-like symptoms as core features of Long COVID even two years post-infection, and highlights the need for subtyping – an important step toward personalized treatment.

The JAMA review summarizes the diagnosis, symptoms, and treatment of POTS. In 30-40% of cases, symptoms begin within 3 months after infections such as SARS-CoV-2, EBV, or influenza. Treatment recommendations include non-pharmacological measures (salt, fluids, compression), individualized exercise, and medications such as beta-blockers, ivabradine, midodrine, fludrocortisone, and pyridostigmine.

POTS frequently occurs as a comorbidity in ME/CFS and Long COVID patients, reflecting autonomic dysfunction. The review provides current diagnostic criteria and treatment options directly relevant to affected patients.

This systematic review analyzed 42 observational studies on neurological alterations in Long COVID. Findings include impaired cortical excitability, abnormal brain oscillatory activity across multiple frequency bands, altered functional connectivity, and structural abnormalities. Some studies also reported imbalances in excitatory-inhibitory neurotransmission and biomarkers suggestive of neuroinflammation or axonal injury—these alterations correlated with persistent fatigue, cognitive dysfunction, and brain fog.

The findings on neuroinflammation and functional brain alterations in Long COVID are directly transferable to ME/CFS, as both conditions share fatigue and cognitive impairment (brain fog) as core symptoms. Objective brain alterations could serve as future diagnostic markers.