This narrative review examines whether exercise lactate could serve as a biomarker for Long COVID. In a clinical observation of 22 patients, mean arterial lactate rose from 1.23 mmol/L at rest to 7.11 mmol/L at peak exercise. The authors emphasize that lactate alone lacks specificity but may be informative as part of a standardized metabolic exercise phenotype together with oxygen uptake and ventilatory thresholds.

Elevated exercise lactate points to mitochondrial dysfunction and impaired energy production, central mechanisms in ME/CFS and Long COVID. An objective exertion biomarker could significantly advance diagnosis and understanding of PEM.

This retrospective cohort study of 5740 children showed that 21-24% experienced persistent symptoms 4-6 weeks after viral respiratory infections (SARS-CoV-2, RSV, influenza). Symptom profiles differed markedly: SARS-CoV-2 predominantly caused neurocognitive and systemic complaints in school-aged children, RSV respiratory and feeding difficulties in infants, and influenza sustained systemic symptoms.

The study demonstrates that post-acute morbidity is not limited to SARS-CoV-2 but also occurs after RSV and influenza, supporting the concept of post-viral fatigue syndromes and highlighting parallels to ME/CFS.

Using single-cell RNA sequencing and flow cytometry, researchers showed that EBV reactivation occurs in B cells before MS relapses, evidenced by elevated LMP-1 transcripts and expansion of atypical CD11c+ B cells displaying EBV gp350 surface protein. Pre-relapse signatures overlapped with MS risk genes and EBNA-2-bound enhancers, suggesting shared regulatory mechanisms between genetic predisposition and viral reactivation.

EBV reactivation is also a central suspected mechanism in ME/CFS. This study provides detailed evidence of how EBV reactivation reprograms the peripheral immune system - a model potentially transferable to ME/CFS symptom flares (post-exertional malaise). The role of atypical B cells and the link between genetic predisposition and viral reactivation are also relevant to ME/CFS.

The review discusses how the SARS-CoV-2 receptor ACE2 is influenced by disturbances in lipid metabolism, potentially driving systemic inflammation and blood-brain barrier damage. The authors link these mechanisms to Long COVID and potentially neurodegenerative processes as seen in Alzheimer's and Parkinson's. Therapeutic strategies including soluble ACE2 and lipid-focused interventions are also discussed.

ACE2 dysregulation, chronic neuroinflammation and endothelial dysfunction are central hypotheses in Long COVID and ME/CFS. The paper addresses potential therapies such as soluble ACE2 which could also be relevant for post-viral conditions.

The review summarizes evidence that high consumption of ultra-processed foods with phosphate additives impairs skeletal muscle energetics. Using 31P-MR spectroscopy, reduced ATP synthesis and greater phosphocreatine depletion during exercise were observed. At the cellular level, elevated phosphate promotes oxidative stress, autophagy, and mitochondrial dysfunction.

The described mechanisms - impaired ATP synthesis, mitochondrial dysfunction, and oxidative stress in muscle - overlap with key disease mechanisms in ME/CFS and may represent a modifiable environmental factor influencing exercise intolerance.

The mouse study shows that olfactory tuft cells regulate baseline inflammation and immune response to influenza infection in the nasal mucosa. Loss of gustatory signaling pathways led to increased inflammation, elevated cytokine production (IL-4, IL-13, IFN-γ), and altered stem cell activation. Findings suggest therapeutic targets for long COVID-related olfactory disorders.

Smell disorders are a common long COVID symptom. The study identifies a mechanism of how viral infections can cause persistent inflammation in the olfactory epithelium and suggests concrete therapeutic approaches.

The study examined older adults with neurologic Long COVID (Neuro-PASC) and found reduced monocyte counts with elevated mitochondrial superoxide, along with disrupted coupling of the ATP synthase pathway with cognitive performance. A 13-gene anchor identified this phenotype and showed that normal coordination between myeloid and lymphoid cells (monocytes and T-cells) is lost in Neuro-PASC. This suggests systemic mitochondrial dysfunction of the immune system as a potential driver of cognitive symptoms.

The study provides biological evidence for cognitive dysfunction (brain fog) in Long COVID and links multiple ME/CFS-relevant mechanisms: mitochondrial dysfunction, oxidative stress, and immune dysregulation. The 13-gene anchor could serve as a potential biomarker.

The study compared gut microbiota of 11 long COVID patients with 11 healthy controls, finding lower diversity, more pro-inflammatory bacteria (e.g. Streptococcus salivarius) and fewer anti-inflammatory bacteria (e.g. Faecalibacterium). Fecal transplants into mice caused lung and intestinal inflammation as well as anxiety-like behavior. Mice also showed worse outcomes during Klebsiella pneumoniae infections, suggesting a causal role of the microbiome.

The study provides causal evidence that altered gut microbiota in persistent long COVID can itself trigger symptoms. Since microbiome dysbiosis is also known in ME/CFS, this opens potential therapeutic avenues such as targeted microbiome modulation.

This review describes how extracellular vesicles (EVs) released after SARS-CoV-2 infection can transport viral proteins like the spike glycoprotein in their native conformation, driving chronic signaling and systemic inflammation. Modern techniques such as cryo-electron tomography now enable detailed structural characterization of these vesicles. EVs are evaluated as promising biomarkers and potential therapeutic platforms for Long COVID.

Viral persistence is a central hypothesis in Long COVID and ME/CFS. EVs may explain how viral antigens remain in the body after acute infection, causing chronic neuroinflammation and vascular injury – potential targets for diagnostics and therapy.

The study analyzed B cells from COVID-19 patients and identified DN2 cells (CD11c+ atypical memory B cells) as the main source of autoantibodies. These cells show increased TLR7 signaling, oxidative stress, and are regulated by transcription factors T-bet and XBP1. Genetic analyses showed DN2 cells have the strongest association with autoimmune risk variants.

Autoantibodies are increasingly discussed as a key mechanism in Long COVID and ME/CFS (e.g., against adrenergic receptors). This study identifies the cellular source of these autoantibodies and could open new therapeutic approaches (e.g., targeted depletion of DN2 cells or TLR7 blockade).

In a human cell model of the blood-brain barrier, inactivated SARS-CoV-2 or spike protein led to loss of barrier integrity. Additionally, inflammatory cytokines and adhesion molecules were upregulated. This suggests that the host's immune response — not direct viral infection — may be a key driver of neurological COVID symptoms.

The findings could explain 'brain fog' and other neurological symptoms in Long COVID and ME/CFS. A leaky blood-brain barrier enables neuroinflammation, a core mechanism of these conditions, and offers a potential target for diagnostics and therapy.

In this largest study of its kind (49 ME/CFS patients, 50 controls), significantly higher concentrations of extracellular vesicles (EVs) were found in ME/CFS patient plasma. Of 424 analyzed proteins, 11 showed different levels, with tissue origin pointing mainly to erythroid cells, hepatocytes and plasma B cells. Differences did not survive multiple testing correction, but the higher EV concentration itself is a notable finding.

Extracellular vesicles could serve as minimally invasive biomarkers for ME/CFS and provide clues about affected tissues (erythrocytes, liver, B cells). This supports the biological basis of the disease and could lead to diagnostic tests.