Tag: 2026

Comprehensive review of myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, debilitating disease that is unexplained and is characterised by persistent unexplained fatigue, Post Exertional Malaise (PEM), cognitive impairment, unrefreshing sleep and multisystem impairment. Despite the high burden of symptoms and the worldwide prevalence, ME/CFS has been poorly understood, underdiagnosed and underfunded. This large-scale review summarises the available evidence regarding the epidemiology, diagnostic progress, main clinical characteristics, pathophysiological theories and therapeutic approaches for ME/CFS.

Despite problems with diagnostic consistency, the lack of validated biomarkers, and historical linkage to psychiatric illness, the recognition of this condition has been delayed and has led to patient marginalisation. The review highlights PEM as a cardinal symptom and reviews the weaknesses in earlier diagnostic criteria, as well as current changes in treatment guidelines, including the formal withdrawal of Graded Exercise Therapy, which has evidence of harm.

New pathophysiological evidence suggests mitochondrial dysfunction, immune dysregulation, autonomic imbalance, neuroinflammation, and alterations in gut microbiome. New diagnostic and therapeutic strategies, such as metabolomic and electrophysiological assays, mTOR inhibitors, and decentralised clinical trial designs, are being studied. This intersection with Long COVID offers a chance to rapidly advance studies of post-infectious chronic diseases. The paper also argues for stringent subtyping, uniform data collection, and ongoing patient participation in research as strategies to surmount challenges of heterogeneity.

Finally, it underscores the critical need for fair funding of research, so biomarker discovery and development of disease-modifying treatments can be achieved. The care of people with ME/CFS is not only a clinical obligation, but also a public health one.

Source: Jeyaraman, M., Jeyaraman, N., Ramasubramanian, S. et al. Comprehensive review of myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med (2026). https://doi.org/10.1186/s12967-026-08833-4 https://link.springer.com/article/10.1186/s12967-026-08833-4 (Full text)

Exploratory clinical and immunological changes following Tixagevimab/Cilgavimab administration in immunodeficient patients with SARS-CoV-2-associated ME/CFS and persistent circulating spike protein

Abstract:

Background: Persistent circulating SARS-CoV-2 spike protein has been proposed as a potential contributor to long-COVID pathophysiology. Whether administration of spike-targeting monoclonal antibodies is followed by changes in spike protein concentrations, autonomic receptor autoantibodies, or clinical outcomes remains uncertain.

Methods: In this prospective, non-randomized observational study, 21 participants were enrolled. Ten immunodeficient patients with long-COVID-associated ME/CFS and detectable circulating spike protein received Tixagevimab/Cilgavimab for SARS-CoV-2 pre-exposure prophylaxis. One patient subsequently withdrew consent, leaving nine patients for paired baseline and 30-day follow-up analyses. Eleven healthy individuals with previous SARS-CoV-2 infection but without long COVID provided descriptive reference data and were not considered an efficacy control group.

Results: β1-adrenergic receptor autoantibody concentrations decreased from 26.8 ± 18.2 to 21.2 ± 14.7 U/ml (unadjusted p = 0.003). No statistically significant changes were observed for β2-adrenergic or M3/M4-muscarinic receptor autoantibodies. Median spike protein concentrations changed from 63 pg/ml (IQR 9-127) to 26 pg/ml (IQR 10-120; p = 0.63), with individual decreases observed in five of nine patients. None of the assessed clinical outcomes changed significantly at group level. Changes in spike protein concentrations were not significantly correlated with changes in the assessed autonomic receptor autoantibodies.

Conclusion: Tixagevimab/Cilgavimab administration was followed by a nominally significant within-patient reduction in β1-adrenergic receptor autoantibody concentrations, but not by conclusive changes in circulating spike protein or clinical outcomes. These findings are preliminary and hypothesis-generating. The small sample size, non-randomized design, brief 30-day follow-up, inclusion of only immunodeficient patients, and absence of an untreated disease-matched control group preclude conclusions regarding therapeutic efficacy.

Source: Seidel M, Anft M, Wiemers L, Seibert FS, Bertram S, Rosiewicz K, Stervbo U, Westhoff TH, Babel N. Exploratory clinical and immunological changes following Tixagevimab/Cilgavimab administration in immunodeficient patients with SARS-CoV-2-associated ME/CFS and persistent circulating spike protein. Immunol Lett. 2026 Oct 7:107247. doi: 10.1016/j.imlet.2026.107247. Epub ahead of print. PMID: 42843426. https://pubmed.ncbi.nlm.nih.gov/42843426/

Patient’s knowledge, doctor’s ignorance: The production of knowledge about myalgic encephalomyelitis

Abstract:

It is usually assumed that patient and doctor know strictly different things: the patient knows the phenomenological aspects of their illness, and the doctor knows its medical aspects. I present a case study, that of myalgic encephalomyelitis, wherein, due to severely dysfunctional institutional knowledge production and transmission mechanisms, the medical aspects of the illness are on the whole better understood by sick people than by their doctors. Indeed, lay scientists within the patient community disseminate and produce science on their disease, ensuring that patients as a whole have reliable knowledge about their disease. By contrast, systemically produced and systemically maintained ignorance on the part of medical professionals is the norm, and may be beyond the specific case study I present.

Source: de Canson C. Patient’s knowledge, doctor’s ignorance: The production of knowledge about myalgic encephalomyelitis. Stud Hist Philos Sci. 2026 Oct 5;120:102224. doi: 10.1016/j.shpsa.2026.102224. Epub ahead of print. PMID: 42832995. https://www.sciencedirect.com/science/article/pii/S003936812600110X (Full text)

Characterizing Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Symptom Burden, Functional Impairment, and Comparison With Adults in the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study

Abstract:

Objectives: To characterize the clinical, functional, and educational characteristics of adolescents with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and compare selected illness domains with adults in the Multi-Site Clinical Assessment of ME/CFS (MCAM) study.

Study design: Baseline cross-sectional data from adolescents aged 10-17 years enrolled in MCAM were analyzed. Standardized measures included the Short Form-36 (SF-36v2), CDC Symptom Inventory (CDC-SI), Multidimensional Fatigue Inventory (MFI-20), and selected domains of the DePaul Questionnaire. Descriptive statistics characterized the pediatric cohort and bivariate analyses compared adolescents with adults enrolled in MCAM.

Results: Forty adolescents (mean age 15.3 years; 52.5% female) were included. Mean illness duration was 4.0 years. Educational disruption was substantial: 64% received homebound or homeschool instruction, 89% missed school because of illness, and participants missed a mean of 10.8 school days during the preceding month. Physical health-related quality of life was substantially impaired. Persistent post-exertional malaise (PEM), unrefreshing sleep, fatigue, and neurocognitive symptoms were common. Compared with adults (n = 595), adolescents had shorter illness duration and better physical functioning, vitality, and social functioning, whereas mental health scores were similar. Adults reported greater burden across several physical symptom domains although many between-group differences were small.

Conclusions: Adolescents with ME/CFS experience substantial multisystem symptom burden, impaired physical functioning and educational disruption. Many core clinical features were similar to those in adults, supporting the need for early recognition and appropriate clinical and educational support.

Source: Weaver SS, Regan JJ, Issa A, Fall EA, Chen Y, Lin JS, Unger ER. Characterizing Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Symptom Burden, Functional Impairment, and Comparison With Adults in the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study. J Pediatr. 2026 Oct 6:115361. doi: 10.1016/j.jpeds.2026.115361. Epub ahead of print. PMID: 42838410. https://www.jpeds.com/article/S0022-3476(26)00389-6/fulltext (Full text)

Evidence for transcriptomic changes impacting muscle contraction in patients with post-acute COVID-19 syndrome

Abstract:

Post-acute COVID-19 syndrome (PACS) overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) but, due to frequent muscle pain and exertional intolerance, neuromuscular disorders are often suspected. We report the results of a comprehensive neuromuscular evaluation in 27 PACS patients (22F/5M; median age 41 ys).

All patients developed chronic fatigue (>6 months), post-exertional malaise, and cognitive impairment, with muscle pain in 88% but no neuromuscular deficits at clinical examination. 18/27 patients were unable to work. All patients fulfilled established ME/CFS diagnostic criteria (CDC 1994, ICC 2011, Inst Medicine 2015, NICE 2021). Electrophysiological studies and CK levels were normal.

Brain 18FDG-PET/MRI (14/27) showed posterior hypometabolism in 8/14. Muscle biopsy (7/27) showed moderate dysimmune changes in 2/7. Exploratory transcriptomic analyses performed in muscle biopsies from PACS patients and pre-COVID controls unveiled in PACS differentially expressed genes in the cytokine and autophagy pathways.

Interestingly, other genes were also differentially expressed in pathways affecting actin, the cytoskeleton, and contraction. Indeed, we found upregulated genes involved in the troponin-tropomyosin complex, a key regulator of muscle contraction through calcium binding. We also found downregulated genes involved in the formation and stabilization of actin bundles at sarcomere Z discs and in mechanical signaling.

These findings indicate that PACS patients with prominent muscular symptoms do not exhibit overt neuromuscular involvement on standard investigations but may show subtle myopathic or dysimmune changes and central metabolic alterations. At the transcriptomic level, the data show an impact on key pathways involved in contraction. The overlap with ME/CFS highlights the importance of careful differential diagnosis and suggests a complex pathophysiology beyond a basic muscle disease.

Source: Gianmarco Severa, Rakel Altabe-Mellul, Alessio Rotini, Peggy Lafuste, Sarah Souvannanorath, Edoardo Malfatti, Emmanuel Itti, Hakim Ahmed-Belkacem, Fred Relaix, Francois Jerome Authier, 3.14P Evidence for transcriptomic changes impacting muscle contraction in patients with post-acute COVID-19 syndrome, Neuromuscular Disorders, Volume 67, Supplement 1, 2026, 106984, ISSN 0960-8966, https://doi.org/10.1016/j.nmd.2026.106984. https://www.sciencedirect.com/science/article/abs/pii/S0960896626006528

FreeSurfer-based amygdala subfield volumetry in long COVID and ME/CFS: clinical and immunological correlations

Abstract:

Background: Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share debilitating symptoms and have been associated with limbic-system dysfunction. We investigated amygdala subfield volumes to identify disease-specific neuroanatomical features and their clinical and immunological correlates.

Methods: We prospectively examined 27 patients with long COVID, 38 patients with ME/CFS, and 47 healthy controls (HCs). Amygdala subfields were segmented using high-resolution 3-T MRI and FreeSurfer software. Group comparisons were performed using analysis of covariance, and partial correlations with clinical and immunological indices, including autoantibodies, plasmablasts, regulatory T cells (Tregs), and Eomesodermin-positive helper T cells (Eomes+ Th cells), were assessed.

Results: Patients with long COVID had nominally larger right cortical nucleus volumes than HCs (raw p = 0.040; Bonferroni-adjusted p = 0.119), whereas patients with ME/CFS had a nominally larger left paralaminar nucleus (raw p = 0.048; Bonferroni-adjusted p = 0.145). In long COVID, G-protein-coupled receptor (GPCR) autoantibodies were nominally negatively associated with right medial nucleus volume. In ME/CFS, performance status was nominally positively associated with the right basal nucleus, right paralaminar nucleus, and right whole amygdala, and plasmablasts were nominally positively associated with the right corticoamygdaloid transition area. No group difference or partial correlation remained significant after correction for multiple testing.

Conclusion: Although no finding survived correction for multiple testing, the exploratory results suggest that amygdala-related structural variation may be relevant to both long COVID and ME/CFS. The nominal, uncorrected within-group patterns centered on olfactory-related amygdala nuclei and GPCR autoantibodies in long COVID, and on amygdala structure, functional severity, and plasmablasts in ME/CFS; however, these patterns do not support a conclusion of between-group differences. These observations are hypothesis-generating and do not establish disease-specific mechanisms. Prespecified validation in larger longitudinal and independent cohorts is required.

Source: Kimura Y, Sato W, Shigemoto Y, Kagaya R, Hayakawa A, Kumazawa Y, Shin I, Amano K, Yamamura T, Sato N. FreeSurfer-based amygdala subfield volumetry in long COVID and ME/CFS: clinical and immunological correlations. Front Neurol. 2026 Sep 16;17:1913553. doi: 10.3389/fneur.2026.1913553. PMID: 42819213; PMCID: PMC13623709. https://pmc.ncbi.nlm.nih.gov/articles/PMC13623709/ (Full text)

Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia are overlapping chronic disorders characterized by fatigue, pain, cognitive dysfunction, sleep disturbance, and multisystem symptoms. Whether peripheral blood DNA methylation reflects diagnostic categories, quantitative symptom burden, or both remains unclear. We aimed to identify DNA methylation axes associated with diagnosis, symptom dimensions, and clinical differences between these conditions.

Methods: This cross-sectional study included 188 women: 73 healthy controls, 71 with ME/CFS, and 44 with fibromyalgia. DNA methylation was profiled in peripheral blood mononuclear cells using the Illumina MethylationEPIC v2 array. Principal component analysis identified latent methylation axes. Linear models adjusted for age, body mass index, and estimated immune-cell composition tested associations with diagnostic group and clinical measures. Region-level methylation analyses, functional enrichment, bootstrap resampling, permutation testing, leave-one-out analyses, and medication/comorbidity sensitivity analyses were performed.

Results: Both patient groups had greater symptom burden than healthy controls but differed clinically. Fibromyalgia showed greater widespread pain, pain catastrophizing, central sensitization inventory scores, and temporal summation, whereas ME/CFS showed greater post-exertional malaise, cognitive symptoms, and lower physical activity. Two methylation axes showed clinically relevant associations. PC5 differentiated ME/CFS from fibromyalgia and healthy controls and was associated mainly with post-exertional malaise and cognitive symptoms. PC6 separated both patient groups from healthy controls but not from each other, and was associated with broader symptom burden, including widespread pain, pain impact, sleep disturbance, visceral symptoms, and temporal summation. The temporal summation association, together with higher widespread pain and temporal summation in fibromyalgia, suggests that PC6 includes a pain-related component extending to experimentally assessed nociceptive summation. Region-level analyses identified 591 PC5-associated and 54 PC6-associated high-confidence differentially methylated regions. Enrichment implicated neuroimmune, metabolic, cytokine, NF-κB, JAK-STAT, TGF-β, and immune-regulatory pathways. Sensitivity analyses supported the stability of the main associations.

Conclusions: Peripheral blood DNA methylation profiles identified partly distinct but overlapping DNA methylation axes in ME/CFS and fibromyalgia. PC5 was aligned with post-exertional malaise and cognitive symptoms, whereas PC6 was aligned with broader pain-related multisystem burden. Independent replication and longitudinal studies are needed to establish clinical utility.

Source: Polli A, Hendrix J, Wyns A, Van Campenhout J, Allard S, Aerts JL, Laeremans T, Xiong H, Buntinx Y, Michiels J, Ben Amar J, Godderis L, Thienpont B, Nijs J. Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden. J Transl Med. 2026 Aug 22;24(1):1222. doi: 10.1186/s12967-026-08824-5. PMID: 42811334. https://link.springer.com/article/10.1186/s12967-026-08824-5 (Full text)

Persistent symptom burden in long-standing systemic lupus erythematosus: a subgroup-focused hypothesis for an SLE-ME/CFS research phenotype

Abstract:

Background: Despite improved control of inflammatory disease activity in systemic lupus erythematosus (SLE), many patients experience persistent fatigue, impaired physical function, cognitive symptoms, sleep disturbance, and reduced exercise tolerance, including during remission. These symptoms are multifactorial and may not be adequately explained by conventional measures of inflammatory activity. Clinical and biological parallels with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that interacting immune, metabolic, vascular, and autonomic mechanisms may contribute to persistent symptom burden in a subgroup of patients with long-standing SLE.

Objective: To develop a subgroup-focused, non-linear, and testable framework for persistent symptoms in SLE by integrating established SLE evidence with carefully distinguished mechanistic insights from ME/CFS research.

Methods: This Commentary is based on a targeted, non-systematic literature synthesis of publications identified in PubMed and Web of Science. Evidence was categorized as direct SLE evidence, evidence from ME/CFS, or cross-condition mechanistic inference. Priority was given to human studies, systematic reviews, meta-analyses, and translational research addressing persistent symptoms, autonomic and endothelial dysfunction, mitochondrial and redox alterations, and neurocognitive manifestations.

Results: We propose a hypothesized SLE-ME/CFS research phenotype characterized by persistent, functionally limiting symptoms despite low inflammatory disease activity or remission. The phenotype includes fatigue lasting at least six months together with post-exertional symptom exacerbation, unrefreshing sleep, cognitive symptoms, and/or orthostatic intolerance, following structured exclusion or assessment of alternative explanations and comorbidities. Direct SLE evidence supports the relevance of residual immune activation, oxidative stress, mitochondrial alterations, endothelial dysfunction, and dysautonomia. Findings from ME/CFS further suggest potentially convergent mechanisms involving impaired cellular energetics, autonomic dysfunction, altered cerebral perfusion, and neuroimmune dysregulation. However, these cross-condition inferences require direct validation in SLE.

Conclusions: Persistent symptom burden in long-standing SLE may reflect a biologically distinct subgroup in which immune, autonomic, vascular, metabolic, and neurocognitive mechanisms interact dynamically. The proposed framework does not define a new diagnostic entity or fixed disease trajectory but provides a hypothesis-generating basis for prospective longitudinal studies. Multidimensional phenotyping may improve patient stratification, biomarker discovery, and supportive care for patients whose symptoms remain disproportionate to conventional measures of disease activity.

Source: Habermann-Horstmeier L. Persistent symptom burden in long-standing systemic lupus erythematosus: a subgroup-focused hypothesis for an SLE-ME/CFS research phenotype. J Transl Med. 2026 Sep 25;24(1):1215. doi: 10.1186/s12967-026-08867-8. PMID: 42806386. https://link.springer.com/article/10.1186/s12967-026-08867-8 (Full text)

Muscle symptoms and a latent physiological symptom-dysregulation factor in ME/CFS: exploratory analyses by sex and age-defined menopausal-status proxy group

Abstract:

Background: Muscle-related symptoms are among the most disabling manifestations of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), yet their position within the broader symptom architecture of the disease remains unclear. We hypothesized that muscle symptoms may represent a candidate integrative symptom within a broader shared symptom-dysregulation structure and their symptom associations differ according to sex and menopausal status.

Methods: Cross-sectional data from 736 individuals with physician-diagnosed ME/CFS enrolled in the APAV-ME/CFS registry were analysed. Muscle problems served as the primary outcome variable. Associations with 14 symptom domains were examined using multivariable logistic regression. Pearson and tetrachoric correlations, exploratory factor analysis, and structural equation modeling (SEM) were used to identify latent symptom structures. Exploratory analyses were stratified by sex, menopausal status, and disease duration.

Results: In the full multivariable model (non-robust estimates), breathing problems (OR 2.49 [95% Conf. Interval: 1.42-4.38], p = 0.001), flu-like symptoms (OR 1.97 [1.14-3.42], p = 0.015), and temperature-regulation disorders (OR 1.97 [1.10-3.51], p = 0.021) independently predicted muscle problems. A reduced physiological model (not-robust estimates) additionally identified cardiovascular symptoms (OR 1.87 [1.09-3.24], p = 0.024) as a significant predictor. Tetrachoric correlations demonstrated substantial latent associations between muscle problems and breathing difficulties (ρ = 0.52), cardiovascular symptoms (ρ = 0.49), temperature-regulation disorders (ρ = 0.49), visual disturbances (ρ = 0.39), and flu-like symptoms (ρ = 0.39). Factor analysis and SEM supported a single latent physiological dysregulation factor with good model fit (RMSEA = 0.046, CFI = 0.971, TLI = 0.952, SRMR = 0.026).

The sex-stratified analyses revealed differences in the pattern of statistically significant symptom associations across the subgroups. However, the overall test of the symptom-by-sex interaction terms did not provide evidence for a statistically established difference in the symptom associations by sex. Thus, the subgroup-specific patterns should primarily be interpreted as descriptive and exploratory. At the individual symptom level, the association between breathing-related symptoms and muscle problems showed a statistically significant interaction with sex, suggesting that this association may differ between women and men. However, this finding should be interpreted cautiously given the non-significant overall interaction test and the wide confidence interval of the interaction estimate.

In women, all five physiological symptoms independently predicted muscle problems, whereas in men only breathing problems and temperature-regulation disorders remained significant. Women classified as premenopausal and postmenopausal based on an age-defined proxy showed different patterns of symptom associations with muscle problems in subgroup-specific analyses. Women in the premenopausal age-proxy group showed significant associations with cardiovascular symptoms, visual disturbances, and temperature-regulation disorders, whereas women classified as postmenopausal showed significant associations with breathing difficulties and flu-like symptoms. However, the overall menopausal-by-symptom interaction was not statistically significant (Wald χ2 (5)=5.96, p = 0.310).

The specified latent physiological factor showed statistical comparability across the cross-sectional disease-duration groups. Gastrointestinal complaints loaded substantially on the latent factor despite lacking an independent association with muscle problems in multivariable regression. Urogenital symptoms also showed a smaller but significant association with the latent factor and substantial item-specific variance.

Conclusions: Muscle symptoms may represent a candidate integrative symptom within a latent physiological symptom-dysregulation factor encompassing respiratory, cardiovascular, thermoregulatory, visual, and flu-like symptoms in this ME/CFS sample. Secondary analyses suggested that gastrointestinal complaints were also part of the broader physiological symptom pattern, although they were not independently associated with muscle problems. The specified latent physiological factor showed no overall statistical evidence of measurement differences across the cross-sectional disease-duration groups. However, subgroup-specific symptom patterns differed descriptively by sex and age-defined menopausal-status proxy group.

Women classified as premenopausal were characterized primarily by cardiovascular, visual, and thermoregulatory symptom associations, whereas women classified as postmenopausal and men showed greater prominence of breathing-related symptoms. Flu-like symptoms were independently associated with muscle problems in the postmenopausal subgroup but not in the premenopausal subgroup. Because the corresponding interaction term was not statistically significant, this subgroup contrast should be interpreted as an exploratory difference in association rather than as evidence of a menopause-specific effect. More broadly, the findings are compatible with the hypothesis that the latent symptom-dysregulation factor may reflect a chronic PEM-associated multisystem response.

Whether this symptom-dysregulation factor corresponds to interacting autonomic, vascular, immunological, and metabolic processes remains to be determined by longitudinal and biomarker-based studies. ME/CFS phenotyping may improve patient stratification and facilitate the development of mechanism-based therapeutic approaches.

Source: Habermann-Horstmeier L, Horstmeier LM. Muscle symptoms and a latent physiological symptom-dysregulation factor in ME/CFS: exploratory analyses by sex and age-defined menopausal-status proxy group. J Transl Med. 2026 Sep 28;24(1):1216. doi: 10.1186/s12967-026-09018-9. PMID: 42806383. https://link.springer.com/article/10.1186/s12967-026-09018-9 (Full text)

High Frequency of HHV-7 Reactivation in Neurological and Neuropsychiatric Long COVID: A Retrospective Observational Study

Abstract:

The neurological and neuropsychiatric manifestations of long COVID remain incompletely understood. Reactivation of latent herpesviruses has been proposed as a contributing mechanism, but human herpesvirus 7 (HHV-7) has received limited attention despite its neurotropic potential. We conducted a retrospective analysis of HHV-7 polymerase chain reaction (PCR) results in 30 patients (18 women and 12 men; age range, 21-55 years) with a neurological/neuropsychiatric long COVID phenotype tested within 24 months of SARS-CoV-2 infection at R.E.D. Laboratories SA, Belgium.

HHV-7 positivity was compared with a historical pre-COVID-19 laboratory reference cohort comprising 320 diagnostic tests performed from 2012 to 2019. HHV-7 positivity was 29.1% (93/320; 95% CI, 24.4-34.3%) in the historical reference cohort and 76.7% (23/30; 95% CI, 59.1-88.2%) in the neurological/neuropsychiatric long COVID cohort. The between-cohort difference was significant using a two-sided Fisher’s exact test (p < 0.000001). All six patients tested within the first 12 months were HHV-7-positive. HHV-7-positive patients frequently reported neuropsychiatric symptoms, and in one longitudinal index case, viral load tracked self-reported symptom severity.

In this patient-initiated retrospective study, HHV-7 positivity was substantially more frequent in the long COVID cohort than in the historical reference cohort. These findings are hypothesis-generating and support prospective investigation of HHV-7 in neurological and neuropsychiatric long COVID.

Source: Ducret D, Mijatovic T. High Frequency of HHV-7 Reactivation in Neurological and Neuropsychiatric Long COVID: A Retrospective Observational Study. Viruses. 2026 Sep 20;18(9):1043. doi: 10.3390/v18091043. PMID: 42797874. https://www.mdpi.com/1999-4915/18/9/1043 (Full text)