Tag: coxsackievirus

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

Abstract:

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.

Source: Hwang, JH., Lee, JS., Oh, HM. et al. Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis. J Transl Med 21, 763 (2023). https://doi.org/10.1186/s12967-023-04635-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04635-0 (Full text)

Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients

Abstract:

Coxsackie B enteroviruses have been implicated repeatedly as agents associated with chronic fatigue syndrome (CFS). The objective of this study was to compare the serological evidence for the presence of Coxsackie B virus neutralising antibody, with the polymerase chain reaction (PCR) detecting a portion of the 5′ nontranslated region (NTR) of the enterovirus genome.

Serum samples from 100 chronic fatigue patients and from 100 healthy comparison patients were used in this study. In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group. Using the neutralisation assay, 34% of study patients were positive, compared to 41% of comparison patients.

In the study group, 66/100 patient results correlated, i.e., they were either positive/positive or negative/negative for both tests. Of those that did not correlate, the majority were PCR-positive/Coxsackie B antibody-negative (21/34).

In the comparison group, 58/100 patient results correlated. Of those that did not, the majority were PCR-negative/Coxsackie B antibody-positive (37/42).

The Coxsackie B antibody neutralisation assay was not able to differentiate the CFS study group from the healthy comparison group, and thus the clinical relevance of this assay may be questioned. The PCR assay did differentiate the two groups with significantly more CFS patients having evidence of enterovirus than the comparison group.

Source: Nairn C, Galbraith DN, Clements GB. Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients. J Med Virol. 1995 Aug;46(4):310-3. http://www.ncbi.nlm.nih.gov/pubmed/7595406

 

Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?

Abstract:

As a test of the hypothesis that elevated titers of viral antibodies in patients with chronic fatigue syndrome (CFS) are due to a nonspecific polyclonal immune response, antibodies to Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and 14 enteroviruses in 20 patients with CFS and 20 age- and gender-matched controls were simultaneously measured.

Similarly, titers of IgG to herpes simplex virus (HSV) types 1 and 2 were measured in 18 of these cases and in the respective controls. IgG to EBV viral capsid antigen (VCA) was present at titers > or = 1:320 in 55% of cases vs. 15% of controls (P = .02).

The geometric mean titers of early antigen antibody to EBV, HHV-6 IgG, and HSV-1 and HSV-2 IgG were not significantly different among cases and controls. Of the 14 enteroviral antibodies tested for, only those to coxsackieviruses B1 and B4 were present at significant titers (> or = 1:8) in cases vs. controls (P = .02 and P = .001, respectively).

Of the cases, 19 (95%) had either an EBV VCA IgG titer > or = 1:320 or a coxsackievirus B1 or B4 antibody titer > or = 1:8, a percentage significantly higher than that of controls (40%; P = .0004). Titers of EBV VCA IgG and coxsackievirus B1 and B4 antibodies were simultaneously elevated in only 20% of cases.

There was no correlation between elevated titers of EBV VCA IgG and IgG to HHV-6, HSV-1, and HSV-2 or antibody to coxsackieviruses B1 and B4 in the cases. The prevalence of reported allergies to medications or other substances was identical in both groups (60%). These findings suggest that in the majority of cases of CFS, elevation of viral antibody titers is not due to a nonspecific polyclonal immune response.

Comment in: Viral antibodies in chronic fatigue syndrome. [Clin Infect Dis. 1995]

 

Source: Manian FA. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response? Clin Infect Dis. 1994 Sep;19(3):448-53. http://www.ncbi.nlm.nih.gov/pubmed/7811864

 

Myalgic encephalomyelitis: postviral fatigue and the heart

Note: This letter appeared in the November 11, 1989 issue of the British Medical Journal.

 

SIR, The controversial subject of myalgic encephalomyelitis has surfaced once more,(1) and I would like to contribute to the debate about its viral origins.

Persistent virus infections impair the specialised functions of cells. These include the synthesis of specific products such as heavy and light myosin chains, melanin, hormones, and immune functions.(2) Evidence of persistent enterovirus infection has been found in both dilated cardiomyopathy,(3-5) an organic disease discussed at a recent symposium,(3) and the more controversial myalgic encephalomyelitis.(6,7)

In murine myocarditis induced by Coxsackie viruses, more severe and lasting disease is associated with immunopathological processes, which include virus specific, cross reactive, and autoimmune reactions.(3, 8, 9) In Coxsackie viral myocarditis and cardiomyopathy of humans the antibodies that cross react with Coxsackie B antigens are reported.(3) Serum samples from patients with.cardiomyopathy may react with cardiac ,B adrenoreceptors, with mitochondrial ADP/ATP carriers, and with cell surface protein of the calcium channel causing calcium overload of myocytes and consequent dysfunction.(3) Thus a complex pattern of pathogenic mechanisms is emerging to explain dilated cardiomyopathy, which was formerly considered to be idiopathic but is now recognised as a late sequel of a proportion of cardiac infections with certain enteroviruses, particularly those of the Coxsackie B group. This does not exclude the possible role of other viruses-for example, arboviruses where these are prevalent-as initiators of such pathogenic processes.

It seems likely that similar immunological and metabolic disturbances in myalgic encephalomyelitis may also result from chronic infection, usually with enteroviruses, providing the organic basis of the postviral fatigue syndrome.(10) This condition is characterised by severe fatiguability and recuperation through rest. The myocardium, however, cannot rest-except terminally. Does “postviral dilated cardiomyopathy” represent the result of postviral fatigue syndrome of the unresting heart?

~NORMAN R GRIST Communicable Diseases (Scotland) Unit, Ruchill Hospital, Glasgow G20 9NB

 

References

1 Harris F, Taitz LS. Damaging diagnoses of myalgic encephalitis in children. BrMedj 1989;299:790. (23 September.)

2 Southern P, Oldstone MBA. Medical consequences of persistent viral infection. N Englj Med 1986;314:359-67.

3 Schultheiss HP, ed. New concepts in viral heart disease. Berlin: Springer, 1988.

4 Bowles NE, Richardson PJ, Olsen EGJ, Archard LC. Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 1986;i: 1120-3.

5 Kandolf R, Kirschner P, Amies D, et al. Enteroviral heart disease: diagnosis by in situ hybridization. In: Schultheiss HP, ed. New concepts in viral heart disease. Berlin: Springer, 1988:337-48.

6 Yousef GE, Mann GF, Smith DG, et al. Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet 1988;i: 146-50.

7 Archard LC, Bowles NE, Behan PO, Bell EJ, Doyle D. Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatinine kinase. J R Soc Med 1988;81:326-9.

8 Huber SA. The role of immune mechanisms in pathogenesis. In: Bendinelli M, Friedman H, eds. Coxsackieviruses, a general update. New York: Plenum, 1988:103-16.

9 Beisel KW, Rose NR. Relationship of coxsackievirus to cardiac autoimmnunity. In: Bendinelli M, Friedmann H, eds. Coxsackievinruses, a general update. New York: Plenum, 1988:271-92.

10 Behan PO, Behan WMH, Bell EJ. The post-viral fatigue syndrome-an analysis of the findings in 50 cases. J Infect 1985;10:21 1-22.

 

Source:  N. R. Grist. Myalgic encephalomyelitis: postviral fatigue and the heart. BMJ. 1989 Nov 11; 299(6709): 1219. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838100/pdf/bmj00258-0049b.pdf