Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis

Mozhgani, Sayed‐Hamidreza; Rajabi, Farid; Qurbani, Mohsen; Erfani, Yousef; Yaslianifard, Somayeh; Moosavi, A. Z.; Pourrostami, Kiomars; Bagheri, Ali; Soleimani, Alireza; Behzadian, Farida; Safavi, Mahshid; Rezaei, Fatemeh

doi:10.1159/000517930

Cited by 11 publications

(10 citation statements)

References 45 publications

(41 reference statements)

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“…While the discovery of the xenotropic murine leukemia virus (MLV)-related virus (XMRV) by Lombardi and colleagues in 2009 [ 29 ] brought disappointment, the suspicion of virus infection as an etiological factor has persisted. This is evident in the ongoing systematic review concerning HHV-6 in ME/CFS patients [ 30 ]. Furthermore, with the prevalence of substantial post-COVID patients suffering from unknown fatigue symptoms even after full recovery, this hypothesis of viral etiology is receiving renewed attention currently [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Hwang,

Lee,

et al. 2023

J Transl Med

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Background Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients. Methods We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased). Results Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen’s d test) compared to both healthy and diseased controls. Conclusion This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

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Section: Discussionmentioning

confidence: 99%

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Hwang,

Lee,

et al. 2023

J Transl Med

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“…Results from a recent meta‐analysis on randomized controlled clinical trials by Mozhgani et al 30 confirm the association of HHV‐6 and CFS in humans. They also indicate a significant increase in the risk of this neuropsychiatric condition when the virus reactivates from a latent or persistent state in the patient.…”

Section: Discussionmentioning

confidence: 78%

“…They are associated with the active reproduction of viral particles in the human body (IgM, IgG to early antigen or p41/38 and IgG to dUTP HHV-6). [4][5][6]29 Results from a recent meta-analysis on randomized controlled clinical trials by Mozhgani et al 30 confirm the association of HHV-6 and CFS in humans. They also indicate a significant increase in the risk of this neuropsychiatric condition when the virus reactivates from a latent or persistent state in the patient.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV‐6 and HHV‐7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis

Maltsev

2022

Microbiology and Immunology

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This study aimed to compare the efficacy of valaciclovir, valganciclovir, and artesunate in treating chronic reactivated human herpesvirus type 6 (HHV-6) and human herpesvirus type 7 (HHV-7) infection associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). From 255 patients (192 cases) with reactivated HHV-6 and HHV-7 infections (confirmed based on blood leukocyte PCR), valaciclovir, valganciclovir, or artesunate was administered at a dose of 3000, 900, and 100 mg/day, respectively, for 3 months (study group). The control group consisted of similar patients with ME/CFS (n = 63) not taking any antiviral drugs. The significance of differences was evaluated by Student's t-test and the nonparametric criterion-the number of Z-signs. Negative PCR results in patients with HHV-6 and HHV-7 treated with valaciclovir was achieved in 26% and 23% (first month), 34%, and 28% (second month), 37% and 34% of cases (third month), respectively (P < 0.05; Z < Z 0.05 ). The same results with valganciclovir were obtained in 35% and 33% (first month), 44% and 39% (second month), 48% and 45% of cases (third month), but with artesunate in 44% and 41% (first month), 57% and 53% (second month), 68% and 63% of cases (third month), respectively (P < 0.05; Z < Z 0.05 ). Artesunate is more effective than valganciclovir and valacyclovir in patients with ME/CFS with reactivated HHV-6 and HHV-7 infections.

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“…IBS was the most commonly examined FSS regarding the previous infections as potential risk factor. There was only one study that examined relationship between a previous infection, a human herpes virus (HHV)-6 infection, and CFS ( Mozhgani et al, 2022 ). The meta-analysis showed a 1.7 times increased risk in individuals with CFS to have a previous HHV-6 infection compared to healthy controls.…”

Section: Resultsmentioning

confidence: 99%

Aetiological understanding of fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome and classificatory analogues: A systematic umbrella review

Kleinstäuber,

Schröder,

Daehler

et al. 2023

Clin. Psychol. Eur.

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Background This umbrella review systematically assesses the variety and relative dominance of current aetiological views within the scientific literature for the three most investigated symptom-defined functional somatic syndromes (FSS) and their classificatory analogues within psychiatry and psychology. Method An umbrella review of narrative and systematic reviews with and without meta-analyses based on a search of electronic databases (PubMed, Web of Science, Embase, PsychINFO) was conducted. Eligible reviews were published in English, focused on research of any kind of aetiological factors in adults diagnosed with fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and somatic symptom disorder (SSD)/somatoform disorder (SFD). Results We included 452 reviews (132 systematic reviews including meta-analyses, 133 systematic reviews, 197 narrative reviews), of which 132 (29%) focused on two or more of the investigated health conditions simultaneously. Across diagnoses, biological factors were addressed in 90% (k = 405), psychological in 33% (k = 150), social in 12% (k = 54), and healthcare factors in 5% (k = 23) of the reviews. The methodological quality of the included systematic reviews (k = 255) was low (low/critically low: 41% [k = 104]; moderate: 49% [k = 126]; high quality: 10% [k = 25]). The high-quality systematic reviews suggest that deficient conditioned pain modulation, genetic factors, changes in the immune, endocrinological, gastrointestinal, cardiovascular, and nervous system, and psychosocial factors such as sexual abuse and pain catastrophizing increase the risk for FSS. Conclusion Only very few systematic reviews have used comprehensive, biopsychosocial disease models to guide the selection of aetiological factors in FSS research. Future research should strive for higher scientific standards and broaden its perspective on these health conditions.

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Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis

Cited by 11 publications

References 45 publications

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV‐6 and HHV‐7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis

Aetiological understanding of fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome and classificatory analogues: A systematic umbrella review

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