Science4ME News BotScience for ME: News in Brief
30 Mar - 5 Apr 2026
🧵 of highlighted #MECFS and #LongCovid research papers being discussed this week on the Science for ME forum.
@mecfs
https://www.s4me.info/threads/news-in-brief-march-2026.49238/post-685296
Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME/CFS — Bragée et al
"pathway analysis […] identified an enrichment of neutrophil degranulation and platelet-related signatures in POTS, and complement cascade and coagulation-related pathways corresponding with severity of ME/CFS"
Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME/CFS - Scientific Reports
This study evaluated the cerebrospinal fluid (CSF) proteomes from 31 patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We quantified 902 proteins, each expressed in at least eleven samples, and systematically categorized clinical factors relevant to ME/CFS symptoms—including autonomic dysfunction, neuroinflammation and metabolic disturbances. Differentially expressed protein and pathway analyses evaluated protein features associated with both postural orthostatic tachycardia syndrome (POTS) status and disease severity among the patients, while ratio-based analysis further explored associations with severity ratings. Data are available via ProteomeXchange with identifier PXD076216. Neutrophil degranulation and platelet activation were enriched in patients with POTS, and several pathways, such as the complement cascade, coagulation-related pathways and IGFBP‑mediated insulin-like growth factor transport, were enriched in severe cases. Ratio-based analysis identified four biologically interpretable severity-associated protein ratios related to cellular stress, extracellular remodelling and immune–neuronal interaction. Together, these findings provide insight into the biological processes associated with clinical heterogeneity in ME/CFS and generate hypotheses for future validation in larger independent cohorts.
DHCR7 Mutation Carriers and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: No Associations According to DecodeME Data — Antoniy Elias Sverdrup et al
Pathophysiological, Translational, and Diagnostic Aspects of ME/CFS: A Focus on Skeletal Muscle Involvement — Giorgio Fanò-Illic et al
"Over the years, our group contributed to demonstrating that muscle alterations in ME/CFS are not secondary to deconditioning but represent primary biochemical and structural abnormalities."
Human Endogenous Retroviruses and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Insights into Their Role in Disease Pathogenesis, Immune Dysregulation, and as Potential Biomarkers and Therapeutic Targets — Krishani Dinali Perera et al
Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Long COVID — Julia Barr et al
"Among those with ME/CFS (n = 11), four had a consistent PoTS profile across assessments, with others alternating between PoTS and OH (n = 4) or PoTS and borderline readings (n = 3). In LC (n = 5), three showed alternating among PoTS, OH, and borderline profiles"
Persistent Fatigue in Long-COVID is Not Associated with Peripheral Inflammatory or Cellular Stress Biomarkers: A Cross-Sectional Controlled Study — Omdal et al
https://www.sciencedirect.com/science/article/pii/S2666354626000591
Association of structural brain changes with cognitive deficits and fatigue in patients with post COVID-19 condition — Schwichtenberg et al
"Imaging analyses identified reduced volumes and reduced complexity of the thalamus correlating with higher levels of fatigue and implicating the thalamus as key brain region involved in fatigue pathophysiology."
Personalized Exercise Training Modulates Red Blood Cell Rheology and Morphology in Long COVID — Anna-Lena Krüger et al
"15 [of 170] completed all phases and formed a predefined finisher subgroup" "Finishers exhibited significantly lower aggregation index values and longer aggregation half-times at initial compared with the total cohort" "Finishers also exhibited a more favorable functional status at the baseline"
Intravenous immunoglobulin treatment for long COVID: a case report of clinical and immunological findings — Marta Camici et al
"Intravenous immunoglobulin administration was associated with rapid clinical improvement, including resolution of fatigue and cognitive symptoms and recovery of functional status, alongside immunological changes consistent with restoration of immune homoeostasis."
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00063-0/abstract
The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID — Gilmar Reis et al
"Fluvoxamine showed sustained benefit across all time points, with effect estimates ranging from 0.06 to 0.10" "metformin did not show a consistent or sustained therapeutic effect on fatigue"
Long COVID disability burden in US adults — Bonuck et al
"Long COVID received 14% of its disability commensurate funding: $106 million vs. $739.8 million. ME/CFS is the most under-funded condition, receiving <1% of its YLD proportionate funding." "Apart from clinical research, addressing Long COVID’s disability burden will require its full recognition as a disability (not just qualification), alongside public health awareness and provider education."
Long COVID disability burden in US adults - Communications Medicine
Bonuck et al. quantified the disability burden of Long COVID in U.S. adults using years lived with disability and compared its NIH funding to that of 68 other conditions by sex predominance. Long COVID receives far less funding than warranted by its burden, with female predominant conditions consistently underfunded, implying that both disability impact and sex disparities should play a greater role in research funding decisions.
Digital physiological biomarkers predict within-person symptom changes in complex chronic illness — Aitken et al
"Leveraging a natural intensive longitudinal data design from mobile health technologies, this study highlighted the potential of daily biometric monitoring to predict symptom fluctuations in individuals with complex chronic conditions."
Digital physiological biomarkers predict within-person symptom changes in complex chronic illness - npj Digital Medicine
Altered heart‑rate variability (HRV) and resting heart rate (HR) are common in many complex chronic conditions. Mobile and wearable technologies now provide real-time, valid measurements of HRV and HR, advancing symptom monitoring and management. The current study integrates a 60-s morning PPG assessment with evening symptom severity reports, yielding a high-density mobile health dataset (n = 4244) with an average of 125 biometric observations per participant. We examined whether within-person fluctuations in HR, HRV, and respiratory rate predicted daily changes in crash, fatigue, and brain fog symptoms and secondarily evaluated model predictive performance. Model fit and variance explained were highest in models that included morning biometrics in addition to prior-day symptom reports and covariates. Within-person increases in HR and decreases in HRV in the morning were associated with worsening symptom reports in the evening. Walk-forward cross-validation showed a statistically significant improvement in model performance when morning biometrics were added to prior-day symptom reports (AUC = 0.82–0.85 vs. 0.73–0.83). These findings represent the prospective utility of mobile health tools for precision monitoring and prediction of real-time symptom exacerbations in complex chronic illness.
Elevated blood viscosity is associated with dysautonomia in long COVID symptoms — Tamariz et al
"We found that [estimated] blood viscosity was associated with both subjective measures of ANS dysregulation, such as the COMPASS-31 and objective measures such as the presence of orthostatic hypotension or POTS."
https://www.sciencedirect.com/science/article/pii/S2666602226000649
Phenotypic overlap of mental health impairment in post-COVID condition and depressive disorders: Insights from the DigiHero cohort — Fasshauer et al
"PHQ-9-based core symptoms such as anhedonia and depressed mood are significantly less pronounced in PCC only as compared to Depression only individuals" "screening instruments should be adapted to capture transdiagnostic and cognitive-affective symptom dimensions relevant to PCC."
https://www.sciencedirect.com/science/article/pii/S0165032726005501
Transcutaneous Auricular Vagal Nerve Stimulation Against Fatigue Syndrome in Patients with Long COVID: Results of the Randomized, Placebo-Controlled Clinical Pilot Trial COVIVA — Gierthmuehlen et al
"Baseline fatigue and quality-of-life scores were markedly impaired compared with normative data."
https://link.springer.com/article/10.1007/s40120-026-00928-w
Transcutaneous Auricular Vagal Nerve Stimulation Against Fatigue Syndrome in Patients with Long COVID: Results of the Randomized, Placebo-Controlled Clinical Pilot Trial COVIVA - Neurology and Therapy
Introduction Fatigue is the most prevalent symptom in “long COVID”, affecting 6–7% of patients after COVID-19 infection. Its pathophysiology remains unclear, with viral persistence, immune dysregulation, and mitochondrial dysfunction among proposed mechanisms. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulatory approach, has been suggested as a potential treatment. Methods We conducted a randomized, sham-controlled, single-blinded pilot study to evaluate adherence and clinical effects of taVNS in long COVID-related fatigue. Forty-five patients were randomized 1:1:1 to sham stimulation, sub-threshold taVNS, or above-threshold taVNS for 4 weeks using the Conformité Européenne (CE)-certified tVNS-L device (25 Hz, 250 µs, 4 h/day). The primary co-endpoints were fatigue severity (MFI-20) and adherence, defined as mean daily stimulation duration. Secondary endpoints included depressive symptoms (BDI-II), health-related quality of life (SF-36), and post-COVID symptom burden (PCS). Results Of 45 enrolled patients (mean age 42.4 years; 73% female), 4 (8.9%) dropped out early. Mean stimulation time was 236 min/day, fulfilling the adherence criterion in > 80% of participants. Adverse events were mild, including skin irritation (6.7%) and vertigo (6.7%). Across all groups, questionnaire scores improved over time; however, no statistically significant differences were observed between the sham and active stimulation groups. Baseline fatigue and quality-of-life scores were markedly impaired compared with normative data. Conclusion taVNS was safe, feasible, and associated with high adherence in long COVID-related fatigue, but showed no superiority over sham stimulation. Larger multicenter trials with more homogeneous populations and objective biomarkers are required to determine whether taVNS confers therapeutic benefit in this condition. Trial Registration The trial was approved by the ethics committee (23/7798) and registered at the German Clinical Trials Register, identifier DRKS00031974.
Feasibility and preliminary effects of a yoga program developed for adults with post COVID-19 condition (Breathe Easy): Pilot randomized controlled trial — Welfordsson et al
"We conducted an open-label, two-group parallel, pilot randomized controlled trial" "there were no statistically significant within-group changes or between group differences in effects on physical or mental HR-QoL"
https://www.sciencedirect.com/science/article/pii/S0965229926000506
Exploring duplication in reviews of Long COVID: 2020–2023 — Raine and Khouja
"We identified significant similarity in the aims and key characteristics of 112 reviews focused on the frequency and/or risk of Long COVID, which were published in the first three years of the pandemic."
https://link.springer.com/article/10.1186/s13643-026-03174-1
Exploring duplication in reviews of Long COVID: 2020–2023 - Systematic Reviews
Background The unnecessary duplication of reviews is a recognised problem in the field of evidence synthesis. This paper reports findings from a study exploring potential duplication of effort in reviews on the frequency and/or risk of Long COVID that were published during the first 3 years of the COVID-19 pandemic. Methods We extracted and summarised the aims and key characteristics of 112 reviews identified from 5 published evidence summaries commissioned by the National Institute for Health and Care Research (NIHR) for the Department of Health and Social Care (DHSC), England, which covered the period from January 2020 to January 2023. Results There was significant similarity in the aims and characteristics of the 112 reviews. We identified 43 reviews reporting on any persistent symptoms/effects and 69 that focused on specific symptoms/effects; overlap in the conditions studied was common. The majority of reviews focused on individuals of any age (n = 62); where restrictions were applied (n = 50), all but six reviews focused on adults. Most reviews focused on both hospitalised and non-hospitalised patients (n = 97), and authors searched the same time periods. Half of authors reported publishing a protocol prospectively (n = 58), and only a minority received specific review funding (n = 39). Conclusions Our findings raise concerns about unnecessary duplication of effort and the extent to which all reviews we assessed will have added substantially to the Long COVID evidence base. Researchers should seek to minimise research redundancy and only conduct new reviews when a genuine knowledge gap exists.