An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID
Main Article Content
Abstract
Viral infection in most people results in a transient immune/inflammatory response resulting in elimination of the virus and recovery where the immune system returns to that of the pre-infectious state. In susceptible people by contrast there is a transition from an acute immune response to a chronic state that can lead to an ongoing lifelong complex post-viral illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. This susceptibility is proposed to be genetic or be primed by prior health history. Complex abnormalities occur in immune cell functions, immune cell metabolism and energy production, and in cytokine immune modulator regulation. The immune system of the brain/central nervous system becomes activated leading to dysfunction in regulation of body physiology and the onset of many neurological symptoms.
A dysfunctional immune system is core to the development of the post-viral condition as shown with diverse strategies of immune profiling. Many studies have shown changes in numbers and activity of immune cells of different phenotypes and their metabolism. Immune regulating cytokines show complex altered patterns and vary with the stage of the disease, and there are elements of associated autoimmunity. These complex changes are accompanied by an altered molecular homeostasis with immune cell transcripts and proteins no longer produced in a tightly regulated manner, reflected in the instability of the epigenetic code that controls gene expression. Potential key elements of the altered immune function in this disease needing further exploration are changes to the gut-brain-immune axis as a result of changes in the microbiome of the gut, and viral reactivation from latent elements of the triggering virus or from a prior viral infection. Long COVID, an Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-like illness, is the post-viral condition that has arisen in large numbers solely from the pandemic virus Severe Acute Respiratory Syndrome Coronovirus-2. With over 760 million cases worldwide, an estimated ~100 million cases of Long COVID have occurred within a short period. This now provides an unprecedented opportunity to understand the progression of these post-viral diseases, and to progress from a research phase mainly documenting the immune changes to considering potential immunotherapies that might improve the overall symptom profile of affected patients, and provide them with a better quality of life.
Article Details
How to Cite
WALKER, Max O.M. et al.
An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID.
Medical Research Archives, [S.l.], v. 11, n. 7.1, july 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4083>. Date accessed: 30 apr. 2024.
doi: https://doi.org/10.18103/mra.v11i7.1.4083.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Tate W, Walker M, Sweetman E, et al. Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses. Front Neurol. 2022;13:877772. doi:10.3389/fneur.2022.877772
2. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. Dec 15 1994;121(12):953-9. doi:10.7326/0003-4819-121-12-199412150-00009
3. Carruthers BM, Jain AK, De Meirleir KL, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome. 2003/01/01 2003;11(1):7-115. doi:10.1300/J092v11n01_02
4. Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011;270(4):327-338. doi:10.1111/j.1365-2796.2011.02428.x
5. WHO. WHO Coronoavirus (COVID-19) dashboard Accessed 10th May, 2023. https://covid19.who.int
6. Jason LA, Conroy KE, Furst J, Vasan K, Katz BZ. Pre-illness data reveals differences in multiple metabolites and metabolic pathways in those who do and do not recover from infectious mononucleosis. Mol Omics. Aug 15 2022;18(7):662-665. doi:10.1039/d2mo00124a
7. Quadt L, Critchley HD, Garfinkel SN. The neurobiology of interoception in health and disease. Ann N Y Acad Sci. Sep 2018;1428(1):112-128. doi:10.1111/nyas.13915
8. Blair A. A quantitative investigation into the personal and family health histories of Long COVID and ME/CFS patients: identifying susceptibility factors and support needs. University of Technology Sydney; 2022.
9. Wong TL, Weitzer DJ. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas). Apr 26 2021;57(5)doi:10.3390/medicina57050418
10. Michelen M, Manoharan L, Elkheir N, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. Sep 2021;6(9)doi:10.1136/bmjgh-2021-005427
11. Crook H, Raza, S., Nowell, J., Young, M., Edison, P. Long covid—mechanisms, risk factors, and management. BMJ. 2021;374:n1648. doi:10.1136/bmj.n1648
12. Hunt J, Blease C, Geraghty KJ. Long Covid at the crossroads: Comparisons and lessons from the treatment of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Health Psychol. Dec 2022;27(14):3106-3120. doi:10.1177/13591053221084494
13. Sukocheva OA, Maksoud R, Beeraka NM, et al. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J Adv Res. Sep 2022;40:179-196. doi:10.1016/j.jare.2021.11.013
14. Gherardi RK, Crépeaux G, Authier FJ. Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system. Autoimmun Rev. Jul 2019;18(7):691-705. doi:10.1016/j.autrev.2019.05.006
15. Cameron B, Flamand L, Juwana H, et al. Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome. J Med Virol. Oct 2010;82(10):1684-8. doi:10.1002/jmv.21873
16. Hatcher S, House A. Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study. Psychol Med. Oct 2003;33(7):1185-92. doi:10.1017/s0033291703008274
17. Schlauch KA, Khaiboullina SF, De Meirleir KL, et al. Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome. Transl Psychiatry. Feb 9 2016;6(2):e730. doi:10.1038/tp.2015.208
18. Smith AK, Fang H, Whistler T, Unger ER, Rajeevan MS. Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome. Neuropsychobiology. 2011;64(4):183-94. doi:10.1159/000326692
19. Dibble JJ, McGrath SJ, Ponting CP. Genetic risk factors of ME/CFS: a critical review. Hum Mol Genet. Sep 30 2020;29(R1):R117-r124. doi:10.1093/hmg/ddaa169
20. Hajdarevic R, Lande A, Mehlsen J, et al. Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci. Brain Behav Immun. May 2022;102:362-369. doi:10.1016/j.bbi.2022.03.010
21. Das S, Taylor K, Kozubek J, Sardell J, Gardner S. Genetic risk factors for ME/CFS identified using combinatorial analysis. J Transl Med. Dec 14 2022;20(1):598. doi:10.1186/s12967-022-03815-8
22. Cliff JM, King EC, Lee JS, et al. Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Immunol. 2019;10:796. doi:10.3389/fimmu.2019.00796
23. Klein J, Wood J, Jaycox J, et al. Distinguishing features of Long COVID identified through immune profiling. medRxiv. 2022:2022.08.09.22278592. doi:10.1101/2022.08.09.22278592
24. Yin K, Peluso MJ, Thomas R, et al. Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2. bioRxiv. Feb 10 2023;doi:10.1101/2023.02.09.527892
25. Ryan FJ, Hope CM, Masavuli MG, et al. Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection. BMC Med. Jan 14 2022;20(1):26. doi:10.1186/s12916-021-02228-6
26. Landay AL, Jessop C, Lennette ET, Levy JA. Chronic fatigue syndrome: clinical condition associated with immune activation. Lancet. Sep 21 1991;338(8769):707-12. doi:10.1016/0140-6736(91)91440-6
27. Komaroff AL. Is human herpesvirus-6 a trigger for chronic fatigue syndrome? J Clin Virol. Dec 2006;37 Suppl 1:S39-46. doi:10.1016/s1386-6532(06)70010-5
28. Komaroff AL, Buchwald DS. Chronic fatigue syndrome: an update. Annu Rev Med. 1998;49:1-13. doi:10.1146/annurev.med.49.1.1
29. Proal AD, VanElzakker MB. Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms. Front Microbiol. 2021;12:698169. doi:10.3389/fmicb.2021.698169
30. See DM, Tilles JG. alpha-Interferon treatment of patients with chronic fatigue syndrome. Immunol Invest. Jan-Mar 1996;25(1-2):153-64. doi:10.3109/08820139609059298
31. Masuda A, Nozoe SI, Matsuyama T, Tanaka H. Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome. Psychosom Med. Nov-Dec 1994;56(6):512-8. doi:10.1097/00006842-199411000-00006
32. Chang CM, Warren JL, Engels EA. Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults. Cancer. Dec 1 2012;118(23):5929-36. doi:10.1002/cncr.27612
33. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue S, Board on the Health of Select P, Institute of M. The National Academies Collection: Reports funded by National Institutes of Health. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. National Academies Press (US)
Copyright 2015 by the National Academy of Sciences. All rights reserved.; 2015.
34. Brenu EW, van Driel ML, Staines DR, et al. Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Transl Med. May 28 2011;9:81. doi:10.1186/1479-5876-9-81
10.1186/1479-5876-9-81.
35. Maher KJ, Klimas NG, Fletcher MA. Chronic fatigue syndrome is associated with diminished intracellular perforin. Clin Exp Immunol. Dec 2005;142(3):505-11. doi:10.1111/j.1365-2249.2005.02935.x
36. Brenu EW, Staines DR, Baskurt OK, et al. Immune and hemorheological changes in chronic fatigue syndrome. J Transl Med. Jan 11 2010;8:1. doi:10.1186/1479-5876-8-1
37. Osińska I, Popko K, Demkow U. Perforin: an important player in immune response. Cent Eur J Immunol. 2014;39(1):109-15. doi:10.5114/ceji.2014.42135
38. Huth TK, Staines D, Marshall-Gradisnik S. ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56 dim CD16+ and CD56 bright CD16 dim/- natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. J Transl Med. Apr 21 2016;14:97. doi:10.1186/s12967-016-0859-z
39. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. May 2008;9(5):503-10. doi:10.1038/ni1582
40. Gianchecchi E, Delfino DV, Fierabracci A. Natural Killer Cells: Potential Biomarkers and Therapeutic Target in Autoimmune Diseases? Front Immunol. 2021;12:616853. doi:10.3389/fimmu.2021.616853
41. Natelson BH, Brunjes DL, Mancini D. Chronic Fatigue Syndrome and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. Sep 7 2021;78(10):1056-1067. doi:10.1016/j.jacc.2021.06.045
42. Bozzini S, Albergati A, Capelli E, et al. Cardiovascular characteristics of chronic fatigue syndrome. Biomed Rep. Jan 2018;8(1):26-30. doi:10.3892/br.2017.1024
43. Wirth K, Scheibenbogen C. A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors. Autoimmun Rev. Jun 2020;19(6):102527. doi:10.1016/j.autrev.2020.102527
44. Fletcher MA, Zeng XR, Maher K, et al. Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26. PLoS One. May 25 2010;5(5):e10817. doi:10.1371/journal.pone.0010817
45. Curriu M, Carrillo J, Massanella M, et al. Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. Mar 20 2013;11:68. doi:10.1186/1479-5876-11-68
46. Tirelli U, Marotta G, Improta S, Pinto A. Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol. Dec 1994;40(6):601-8. doi:10.1111/j.1365-3083.1994.tb03511.x
47. Ford B, A. Bradley, and A. Bansal. Altered functional T cell subset populations and cytokine profile in patients with chronic fatigue syndrome: A pilot study. Journal of Chronic Diseases and Managment. 2016;1(1):1-9.
48. Bradley AS, Ford B, Bansal AS. Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls. Clin Exp Immunol. Apr 2013;172(1):73-80. doi:10.1111/cei.12043
49. Helliwell AM, Stockwell PA, Edgar CD, Chatterjee A, Tate WP. Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci. Oct 6 2022;23(19)doi:10.3390/ijms231911852
50. Tate WP, Walker MOM, Peppercorn K, Blair ALH, Edgar CD. Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID. Int J Mol Sci. 2023;24(6):5124.
51. Glynne P, Tahmasebi N, Gant V, Gupta R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med. Jan 2022;70(1):61-67. doi:10.1136/jim-2021-002051
52. Jubel JM, Barbati ZR, Burger C, Wirtz DC, Schildberg FA. The Role of PD-1 in Acute and Chronic Infection. Front Immunol. 2020;11:487. doi:10.3389/fimmu.2020.00487
53. Mandarano AH, Maya J, Giloteaux L, et al. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. Mar 2 2020;130(3):1491-1505. doi:10.1172/JCI132185
10.1172/JCI132185.
54. Booth NE, Myhill S, McLaren-Howard J. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med. 2012;5(3):208-20.
55. Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2(1):1-16.
56. Silvestre-Roig C, Fridlender ZG, Glogauer M, Scapini P. Neutrophil Diversity in Health and Disease. Trends Immunol. Jul 2019;40(7):565-583. doi:10.1016/j.it.2019.04.012
57. Nguyen T, Staines D, Johnston S, Marshall-Gradisnik S. Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/ chronic fatigue syndrome patients: A preliminary investigation. Asian Pac J Allergy Immunol. Jun 2019;37(2):102-108. doi:10.12932/ap-011117-0188
58. Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P. Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome. PLoS One. 2018;13(2):e0192817. doi:10.1371/journal.pone.0192817
59. Jahanbani F, Maynard RD, Sing JC, et al. Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study. PLoS One. 2022;17(8):e0272703. doi:10.1371/journal.pone.0272703
60. Komaroff AL. Inflammation correlates with symptoms in chronic fatigue syndrome. Proc Natl Acad Sci U S A. Aug 22 2017;114(34):8914-8916. doi:10.1073/pnas.1712475114
61. Montoya JG, Holmes TH, Anderson JN, et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci U S A. Aug 22 2017;114(34):E7150-E7158. doi:10.1073/pnas.1710519114
10.1073/pnas.1710519114. Epub 2017 Jul 31.
62. VanElzakker MB, Brumfield SA, Lara Mejia PS. Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods. Front Neurol. 2018;9:1033. doi:10.3389/fneur.2018.01033
63. Visser J, Graffelman W, Blauw B, et al. LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. J Neuroimmunol. Oct 1 2001;119(2):343-9. doi:10.1016/s0165-5728(01)00400-3
64. Long D, Chen Y, Wu H, Zhao M, Lu Q. Clinical significance and immunobiology of IL-21 in autoimmunity. J Autoimmun. May 2019;99:1-14. doi:10.1016/j.jaut.2019.01.013
65. Wang Q, Liu J. Regulation and Immune Function of IL-27. Adv Exp Med Biol. 2016;941:191-211. doi:10.1007/978-94-024-0921-5_9
66. Komai T, Inoue M, Okamura T, et al. Transforming Growth Factor-β and Interleukin-10 Synergistically Regulate Humoral Immunity via Modulating Metabolic Signals. Front Immunol. 2018;9:1364. doi:10.3389/fimmu.2018.01364
67. Liao W, Lin JX, Leonard WJ. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol. Oct 2011;23(5):598-604. doi:10.1016/j.coi.2011.08.003
68. Gadani SP, Cronk JC, Norris GT, Kipnis J. IL-4 in the brain: a cytokine to remember. J Immunol. Nov 1 2012;189(9):4213-9. doi:10.4049/jimmunol.1202246
69. Stringer EA, Baker KS, Carroll IR, et al. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. J Transl Med. Apr 9 2013;11:93. doi:10.1186/1479-5876-11-93
70. Taylor EB. The complex role of adipokines in obesity, inflammation, and autoimmunity. Clin Sci (Lond). Mar 26 2021;135(6):731-752. doi:10.1042/cs20200895
71. Hornig M, Montoya JG, Klimas NG, et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Sci Adv. Feb 2015;1(1)doi:10.1126/sciadv.1400121
72. Kavyani B, Lidbury BA, Schloeffel R, et al. Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle? Cell Mol Life Sci. Jul 11 2022;79(8):412. doi:10.1007/s00018-022-04380-5
73. Phetsouphanh C, Darley DR, Wilson DB, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. Feb 2022;23(2):210-216. doi:10.1038/s41590-021-01113-x
74. Schultheiß C, Willscher E, Paschold L, et al. The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. Cell Rep Med. Jun 21 2022;3(6):100663. doi:10.1016/j.xcrm.2022.100663
75. Queiroz MAF, Neves P, Lima SS, et al. Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome. Front Cell Infect Microbiol. 2022;12:922422. doi:10.3389/fcimb.2022.922422
76. Williams ES, Martins TB, Shah KS, et al. Cytokine Deficiencies in Patients with Long-COVID. J Clin Cell Immunol. 2022;13(6)
77. Low RN, Low RJ, Akrami A. A review of cytokine-based pathophysiology of Long COVID symptoms. Front Med (Lausanne). 2023;10:1011936. doi:10.3389/fmed.2023.1011936
78. Bekkering S, Domínguez-Andrés J, Joosten LAB, Riksen NP, Netea MG. Trained Immunity: Reprogramming Innate Immunity in Health and Disease. Annu Rev Immunol. Apr 26 2021;39:667-693. doi:10.1146/annurev-immunol-102119-073855
79. Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. Mar 2009;23(3):327-37. doi:10.1016/j.bbi.2008.11.005
80. Sumida T, Tsuboi H, Iizuka M, Asashima H, Matsumoto I. Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren's syndrome. Mod Rheumatol. Sep 2013;23(5):841-5. doi:10.1007/s10165-012-0788-5
81. Wallukat G, Schimke I. Agonistic autoantibodies directed against G-protein-coupled receptors and their relationship to cardiovascular diseases. Semin Immunopathol. May 2014;36(3):351-63. doi:10.1007/s00281-014-0425-9
82. Li J, Zhang Q, Liao Y, Zhang C, Hao H, Du J. The value of acetylcholine receptor antibody in children with postural tachycardia syndrome. Pediatr Cardiol. Jan 2015;36(1):165-70. doi:10.1007/s00246-014-0981-8
83. Loebel M, Grabowski P, Heidecke H, et al. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. Brain Behav Immun. Feb 2016;52:32-39. doi:10.1016/j.bbi.2015.09.013
84. Sur LM, Floca E, Sur DG, Colceriu MC, Samasca G, Sur G. Antinuclear Antibodies: Marker of Diagnosis and Evolution in Autoimmune Diseases. Lab Med. Jul 5 2018;49(3):e62-e73. doi:10.1093/labmed/lmy024
85. Slota C, Shi A, Chen G, Bevans M, Weng NP. Norepinephrine preferentially modulates memory CD8 T cell function inducing inflammatory cytokine production and reducing proliferation in response to activation. Brain Behav Immun. May 2015;46:168-79. doi:10.1016/j.bbi.2015.01.015
86. Sweetman E, Kleffmann T, Edgar C, de Lange M, Vallings R, Tate W. A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction. J Transl Med. Sep 24 2020;18(1):365. doi:10.1186/s12967-020-02533-3
87. Faraz A, Luyen Tien V, Hongya Z, et al. Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation. bioRxiv. 2022:2022.10.13.512091. doi:10.1101/2022.10.13.512091
88. Van Booven DJ, Gamer J, Joseph A, et al. Stress-Induced Transcriptomic Changes in Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Reveal Disrupted Immune Signatures. Int J Mol Sci. Jan 31 2023;24(3)doi:10.3390/ijms24032698
89. Sweetman E, Ryan M, Edgar C, MacKay A, Vallings R, Tate W. Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome. Int J Immunopathol Pharmacol. Jan-Dec 2019;33:2058738418820402. doi:10.1177/2058738418820402
90. Fernandez-Guerra P, Gonzalez-Ebsen AC, Boonen SE, et al. Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study. Biomolecules. Jun 29 2021;11(7)doi:10.3390/biom11070961
91. Germain A, Levine SM, Hanson MR. In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling. Proteomes. Jan 29 2021;9(1)doi:10.3390/proteomes9010006
92. Helliwell AM, Sweetman EC, Stockwell PA, Edgar CD, Chatterjee A, Tate WP. Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions. Clin Epigenetics. Nov 4 2020;12(1):167. doi:10.1186/s13148-020-00960-z
93. de Vega WC, Vernon SD, McGowan PO. DNA methylation modifications associated with chronic fatigue syndrome. PLoS One. 2014;9(8):e104757. doi:10.1371/journal.pone.0104757
94. de Vega WC, McGowan PO. The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome: deciphering complex phenotypes. Epigenomics. Nov 2017;9(11):1337-1340. doi:10.2217/epi-2017-0106
95. Herrera S, de Vega WC, Ashbrook D, Vernon SD, McGowan PO. Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Epigenetics. 2018;13(12):1174-1190. doi:10.1080/15592294.2018.1549769
96. Brenu EWS, D.R.; Marshall-Gradisnik S.M. . Methylation Profile of CD4+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Clin Cell Immunol. 2014;5(228)
97. Trivedi MS, Oltra E, Sarria L, et al. Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns. PLoS One. 2018;13(7):e0201066. doi:10.1371/journal.pone.0201066
98. de Vega WC, Erdman L, Vernon SD, Goldenberg A, McGowan PO. Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome. Epigenomics. May 2018;10(5):539-557. doi:10.2217/epi-2017-0150
99. Nguyen T, Johnston S, Clarke L, Smith P, Staines D, Marshall-Gradisnik S. Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels. Clin Exp Immunol. Feb 2017;187(2):284-293. doi:10.1111/cei.12882
100. Held K, Tóth BI. TRPM3 in Brain (Patho)Physiology. Front Cell Dev Biol. 2021;9:635659. doi:10.3389/fcell.2021.635659
101. Vriens J, Owsianik G, Hofmann T, et al. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron. May 12 2011;70(3):482-94. doi:10.1016/j.neuron.2011.02.051
102. Cabanas H, Muraki K, Staines D, Marshall-Gradisnik S. Naltrexone Restores Impaired Transient Receptor Potential Melastatin 3 Ion Channel Function in Natural Killer Cells From Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Front Immunol. 2019;10:2545. doi:10.3389/fimmu.2019.02545
103. Nguyen T, Staines D, Nilius B, Smith P, Marshall-Gradisnik S. Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients. Biol Res. May 31 2016;49(1):27. doi:10.1186/s40659-016-0087-2
104. Cabanas H, Muraki K, Eaton N, Balinas C, Staines D, Marshall-Gradisnik S. Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. Mol Med. Aug 14 2018;24(1):44. doi:10.1186/s10020-018-0046-1
105. Marshall-Gradisnik S, Huth T, Chacko A, Johnston S, Smith P, Staines D. Natural killer cells and single nucleotide polymorphisms of specific ion channels and receptor genes in myalgic encephalomyelitis/chronic fatigue syndrome. Appl Clin Genet. 2016;9:39-47. doi:10.2147/tacg.S99405
106. Dembla S, Behrendt M, Mohr F, et al. Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels. Elife. Aug 15 2017;6doi:10.7554/eLife.26280
107. Singh DS, A. . Naltrexone. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK534811
108. Weinstock L. EFFICACY OF LOW DOSE NALTREXONE IN PATIENTS WITH CROHN’S COLITIS AND ILEITIS. Inflammatory Bowel Diseases. 2022;28(Supplement_1):S106-S107. doi:10.1093/ibd/izac015.172
109. Parker CE, Nguyen TM, Segal D, MacDonald JK, Chande N. Low dose naltrexone for induction of remission in Crohn's disease. Cochrane Database Syst Rev. Apr 1 2018;4(4):Cd010410. doi:10.1002/14651858.CD010410.pub3
110. Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. Feb 2013;65(2):529-38. doi:10.1002/art.37734
111. Cree BA, Kornyeyeva E, Goodin DS. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. Aug 2010;68(2):145-50. doi:10.1002/ana.22006
112. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. Apr 2014;33(4):451-9. doi:10.1007/s10067-014-2517-2
113. Mapunda JA, Tibar H, Regragui W, Engelhardt B. How Does the Immune System Enter the Brain? Front Immunol. 2022;13:805657. doi:10.3389/fimmu.2022.805657
114. Norris GT, Kipnis J. Immune cells and CNS physiology: Microglia and beyond. J Exp Med. Jan 7 2019;216(1):60-70. doi:10.1084/jem.20180199
115. Nakatomi Y, Mizuno K, Ishii A, et al. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An (1)(1)C-(R)-PK11195 PET Study. J Nucl Med. Jun 2014;55(6):945-50. doi:10.2967/jnumed.113.131045
116. Visser D, Golla SSV, Verfaillie SCJ, et al. Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET. medRxiv. 2022:2022.06.02.22275916. doi:10.1101/2022.06.02.22275916
117. Nelson T, Zhang LX, Guo H, Nacul L, Song X. Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings. Front Neurol. 2021;12:769511. doi:10.3389/fneur.2021.769511
118. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). Oct 2021;53(10):737-754. doi:10.1080/23744235.2021.1924397
119. Lull ME, Block ML. Microglial activation and chronic neurodegeneration. Neurotherapeutics. Oct 2010;7(4):354-65. doi:10.1016/j.nurt.2010.05.014
120. Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH. Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson's disease. J Neurosci. Nov 1 2001;21(21):8447-55. doi:10.1523/jneurosci.21-21-08447.2001
121. Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity. Oct 2005;23(4):344-6. doi:10.1016/j.immuni.2005.10.001
122. Pais TF, Figueiredo C, Peixoto R, Braz MH, Chatterjee S. Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway. J Neuroinflammation. Oct 9 2008;5:43. doi:10.1186/1742-2094-5-43
123. Tracey KJ. The inflammatory reflex. Nature. Dec 19-26 2002;420(6917):853-9. doi:10.1038/nature01321
124. Mackay A, Tate WP. A compromised paraventricular nucleus within a dysfunctional hypothalamus: A novel neuroinflammatory paradigm for ME/CFS. International Journal of Immunopathology and Pharmacology. 2018;32:2058738418812342. doi:10.1177/2058738418812342
125. Mackay A. A Paradigm for Post-Covid-19 Fatigue Syndrome Analogous to ME/CFS. Hypothesis and Theory. Frontiers in Neurology. 2021-August-02 2021;12doi:10.3389/fneur.2021.701419
126. Bested AC, Saunders PR, Logan AC. Chronic fatigue syndrome: neurological findings may be related to blood–brain barrier permeability. Medical Hypotheses. 2001/08/01/ 2001;57(2):231-237. doi:https://doi.org/10.1054/mehy.2001.1306
127. Kamimura D, Ohki T, Arima Y, Murakami M. Gateway reflex: neural activation-mediated immune cell gateways in the central nervous system. Int Immunol. Jun 26 2018;30(7):281-289. doi:10.1093/intimm/dxy034
128. Sabharwal L, Kamimura D, Meng J, et al. The Gateway Reflex, which is mediated by the inflammation amplifier, directs pathogenic immune cells into the CNS. J Biochem. Dec 2014;156(6):299-304. doi:10.1093/jb/mvu057
129. Gate D, Tapp E, Leventhal O, et al. CD4(+) T cells contribute to neurodegeneration in Lewy body dementia. Science. Nov 12 2021;374(6569):868-874. doi:10.1126/science.abf7266
130. Sampson TR, Debelius JW, Thron T, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. Dec 1 2016;167(6):1469-1480 e12. doi:10.1016/j.cell.2016.11.018
131. Schroeder BO, Backhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. Oct 2016;22(10):1079-1089. doi:10.1038/nm.4185
132. König RS, Albrich WC, Kahlert CR, et al. The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Front Immunol. 2021;12:628741. doi:10.3389/fimmu.2021.628741
133. Ariza ME. Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: The Human Herpesviruses Are Back! Biomolecules. 2021;11(2). doi:10.3390/biom11020185
134. Williams Ph DM, Cox B, Lafuse Ph DW, Ariza ME. Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clin Ther. May 2019;41(5):848-863. doi:10.1016/j.clinthera.2019.04.009
135. Wessely S. Chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. Aug 1991;54(8):669-71. doi:10.1136/jnnp.54.8.669
136. Vink M, Vink-Niese A. Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review. Health Psychol Open. Jan-Jun 2019;6(1):2055102919840614. doi:10.1177/2055102919840614
137. Vink M, Vink-Niese A. The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Diseases. Jan 16 2023;11(1)doi:10.3390/diseases11010011
138. Shepherd CB. PACE trial claims for recovery in myalgic encephalomyelitis/chronic fatigue syndrome - true or false? It's time for an independent review of the methodology and results. J Health Psychol. Aug 2017;22(9):1187-1191. doi:10.1177/1359105317703786
139. Hodges L, Nielsen T, Cochrane D, Baken D. The physiological time line of post-exertional malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). TRANSLATIONAL SPORTS MEDICINE. 2020;3(3):243-249. doi:https://doi.org/10.1002/tsm2.133
140. Rekeland IG, Fosså A, Lande A, et al. Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study. Front Med (Lausanne). 2020;7:162. doi:10.3389/fmed.2020.00162
141. Bolton MJ, Chapman BP, Van Marwijk H. Low-dose naltrexone as a treatment for chronic fatigue syndrome. BMJ Case Rep. Jan 6 2020;13(1)doi:10.1136/bcr-2019-232502
142. Welsh RM. Natural killer cells and interferon. Crit Rev Immunol. 1984;5(1):55-93.
143. Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. Am J Med. Nov 1990;89(5):561-8. doi:10.1016/0002 9343(90)90173-b
144. Peterson PK, Shepard J, Macres M, et al. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med. Nov 1990;89(5):554-60. doi:10.1016/0002-9343(90)90172-a
145. Rowe KS. Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents. J Psychiatr Res. Jan-Feb 1997;31(1):133-47. doi:10.1016/s0022-3956(96)00047-7
146. Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, et al. Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome. Am J Med. Jul 1997;103(1):38-43. doi:10.1016/s0002-9343(97)90045-0
147. Glazachev OS, Dudnik Е N, Zagaynaya EE. [Pharmacological treatment of patients with chronic fatigue syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(4):40-44. Medikamentoznaia terapiia patsientov s sindromom khronicheskoĭ ustalosti. doi:10.17116/jnevro20171174140-44
148. Park SB, Kim KN, Sung E, Lee SY, Shin HC. Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study. Biol Pharm Bull. May 1 2016;39(5):674-9. doi:10.1248/bpb.b15-00623
149. Montoya JG, Kogelnik AM, Bhangoo M, et al. Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J Med Virol. Dec 2013;85(12):2101-9. doi:10.1002/jmv.23713
150. Wood E, Hall KH, Tate W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 'long-haulers'? Chronic Dis Transl Med. Mar 2021;7(1):14-26. doi:10.1016/j.cdtm.2020.11.002
151. Lebedeva AV, Shchukin IA, Soldatov MA, et al. [Asthenia, emotional disorders and quality of life of patients with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(10 Pt 2):99-104. Asteniia, émotsional'nye rasstroĭstva i kachestvo zhizni u patsientov s rasseiannym sklerozom.
152. Tereshin AE, Kiryanova VV, Reshetnik DA. Correction of Mitochondrial Dysfunction in the Complex Rehabilitation of COVID-19 Patients. Neurosci Behav Physiol. 2022;52(4):511-514. doi:10.1007/s11055-022-01269-5
153. Ozel O, Vaughn CB, Eckert SP, Jakimovski D, Lizarraga AA, Weinstock-Guttman B. Dimethyl Fumarate in the Treatment of Relapsing-Remitting Multiple Sclerosis: Patient Reported Outcomes and Perspectives. Patient Relat Outcome Meas. 2019;10:373-384. doi:10.2147/prom.S168095
154. Ortiz JF, Khan SA, Salem A, Lin Z, Iqbal Z, Jahan N. Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug. Cureus. Oct 6 2020;12(10):e10818. doi:10.7759/cureus.10818
155. Cash A, Kaufman DL. Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial. J Transl Med. Jun 28 2022;20(1):295. doi:10.1186/s12967-022-03488-3
156. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. Mar 19 2009;1(1):6. doi:10.1186/1757-4749-1-6
157. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. Jan 26 2009;8:4. doi:10.1186/1475-2891-8-4
158. Venturini L, Bacchi S, Capelli E, Lorusso L, Ricevuti G, Cusa C. Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study. Oxid Med Cell Longev. 2019;2019:1684198. doi:10.1155/2019/1684198
159. Groeger D, O'Mahony L, Murphy EF, et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. Jul-Aug 2013;4(4):325-39. doi:10.4161/gmic.25487
160. Borody TJ, Nowak A, Finlayson S. The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy. Other Journal Article. Journal of the Australasian College of Nutritional and Environmental Medicine. 2012;31(3):3-8.
161. Kenyon JN, Coe S, Izadi H. A retrospective outcome study of 42 patients with Chronic Fatigue Syndrome, 30 of whom had Irritable Bowel Syndrome. Half were treated with oral approaches, and half were treated with Faecal Microbiome Transplantation. Human Microbiome Journal. 2019/08/01/ 2019;13:100061. doi:https://doi.org/10.1016/j.humic.2019.100061
162. Fluge Ø, Bruland O, Risa K, et al. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One. 2011;6(10):e26358. doi:10.1371/journal.pone.0026358
163. Fluge Ø, Rekeland IG, Lien K, et al. B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. May 7 2019;170(9):585-593. doi:10.7326/m18-1451
164. Park SB, Kim K-N, Sung E, Lee SY, Shin HC. Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study. Biological and Pharmaceutical Bulletin. 2016;39(5):674-679. doi:10.1248/bpb.b15-00623
165. McInnes IB, Gravallese EM. Immune-mediated inflammatory disease therapeutics: past, present and future. Nat Rev Immunol. Oct 2021;21(10):680-686. doi:10.1038/s41577-021-00603-1
166. Brownlie H, Speight N. Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare (Basel). Nov 12 2021;9(11)doi:10.3390/healthcare9111546
167. Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520. doi:10.3389/fimmu.2014.00520
168. Anthony RM, Nimmerjahn F. The role of differential IgG glycosylation in the interaction of antibodies with FcγRs in vivo. Curr Opin Organ Transplant. Feb 2011;16(1):7-14. doi:10.1097/MOT.0b013e328342538f
169. Leusen JHW, Nimmerjahn F. The Role of IgG in Immune Responses. In: Nimmerjahn F, ed. Molecular and Cellular Mechanisms of Antibody Activity. Springer New York; 2013:85-112.
170. Aalberse R. The role of IgG antibodies in allergy and immunotherapy. Allergy. Jul 2011;66 Suppl 95:28-30. doi:10.1111/j.1398-9995.2011.02628.x
171. Fillatreau S. B cells and their cytokine activities implications in human diseases. Clin Immunol. Jan 2018;186:26-31. doi:10.1016/j.clim.2017.07.020
172. Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. Feb 14 2008;358(7):676-88. doi:10.1056/NEJMoa0706383
173. Scher JU. B-cell therapies for rheumatoid arthritis. Bull NYU Hosp Jt Dis. 2012;70(3):200-3.
174. Sotzny F, Blanco J, Capelli E, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease. Autoimmun Rev. Jun 2018;17(6):601-609. doi:10.1016/j.autrev.2018.01.009
175. Behan WM, More IA, Behan PO. Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol. 1991;83(1):61-5. doi:10.1007/bf00294431
176. Missailidis D, Annesley SJ, Allan CY, et al. An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients. Int J Mol Sci. Feb 6 2020;21(3)doi:10.3390/ijms21031074
177. Castro-Marrero J, Cordero MD, Sáez-Francas N, et al. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. Nov 20 2013;19(15):1855-60. doi:10.1089/ars.2013.5346
178. Cordero MD, de Miguel M, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AM. Oxidative stress and mitochondrial dysfunction in fibromyalgia. Neuro Endocrinol Lett. 2010;31(2):169-73.
179. Castro-Marrero J, Domingo JC, Cordobilla B, et al. Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. Apr 2022;36(10-12):729-739. doi:10.1089/ars.2022.0018
180. Gueven N, Ravishankar P, Eri R, Rybalka E. Idebenone: When an antioxidant is not an antioxidant. Redox Biol. Jan 2021;38:101812. doi:10.1016/j.redox.2020.101812
181. Paul BD, Lemle MD, Komaroff AL, Snyder SH. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. Aug 24 2021;118(34)doi:10.1073/pnas.2024358118
182. Walker MOM, Hall KH, Peppercorn K, Tate WP. The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medical Research Archives. 2022;10(9)
183. Gareau MG, Barrett KE. Role of the microbiota-gut-brain axis in postacute COVID syndrome. Am J Physiol Gastrointest Liver Physiol. Apr 1 2023;324(4):G322-g328. doi:10.1152/ajpgi.00293.2022
184. Mullish BH, Quraishi MN, Segal JP, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut. Nov 2018;67(11):1920-1941. doi:10.1136/gutjnl-2018-316818
2. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. Dec 15 1994;121(12):953-9. doi:10.7326/0003-4819-121-12-199412150-00009
3. Carruthers BM, Jain AK, De Meirleir KL, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome. 2003/01/01 2003;11(1):7-115. doi:10.1300/J092v11n01_02
4. Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011;270(4):327-338. doi:10.1111/j.1365-2796.2011.02428.x
5. WHO. WHO Coronoavirus (COVID-19) dashboard Accessed 10th May, 2023. https://covid19.who.int
6. Jason LA, Conroy KE, Furst J, Vasan K, Katz BZ. Pre-illness data reveals differences in multiple metabolites and metabolic pathways in those who do and do not recover from infectious mononucleosis. Mol Omics. Aug 15 2022;18(7):662-665. doi:10.1039/d2mo00124a
7. Quadt L, Critchley HD, Garfinkel SN. The neurobiology of interoception in health and disease. Ann N Y Acad Sci. Sep 2018;1428(1):112-128. doi:10.1111/nyas.13915
8. Blair A. A quantitative investigation into the personal and family health histories of Long COVID and ME/CFS patients: identifying susceptibility factors and support needs. University of Technology Sydney; 2022.
9. Wong TL, Weitzer DJ. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas). Apr 26 2021;57(5)doi:10.3390/medicina57050418
10. Michelen M, Manoharan L, Elkheir N, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. Sep 2021;6(9)doi:10.1136/bmjgh-2021-005427
11. Crook H, Raza, S., Nowell, J., Young, M., Edison, P. Long covid—mechanisms, risk factors, and management. BMJ. 2021;374:n1648. doi:10.1136/bmj.n1648
12. Hunt J, Blease C, Geraghty KJ. Long Covid at the crossroads: Comparisons and lessons from the treatment of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Health Psychol. Dec 2022;27(14):3106-3120. doi:10.1177/13591053221084494
13. Sukocheva OA, Maksoud R, Beeraka NM, et al. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J Adv Res. Sep 2022;40:179-196. doi:10.1016/j.jare.2021.11.013
14. Gherardi RK, Crépeaux G, Authier FJ. Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system. Autoimmun Rev. Jul 2019;18(7):691-705. doi:10.1016/j.autrev.2019.05.006
15. Cameron B, Flamand L, Juwana H, et al. Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome. J Med Virol. Oct 2010;82(10):1684-8. doi:10.1002/jmv.21873
16. Hatcher S, House A. Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study. Psychol Med. Oct 2003;33(7):1185-92. doi:10.1017/s0033291703008274
17. Schlauch KA, Khaiboullina SF, De Meirleir KL, et al. Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome. Transl Psychiatry. Feb 9 2016;6(2):e730. doi:10.1038/tp.2015.208
18. Smith AK, Fang H, Whistler T, Unger ER, Rajeevan MS. Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome. Neuropsychobiology. 2011;64(4):183-94. doi:10.1159/000326692
19. Dibble JJ, McGrath SJ, Ponting CP. Genetic risk factors of ME/CFS: a critical review. Hum Mol Genet. Sep 30 2020;29(R1):R117-r124. doi:10.1093/hmg/ddaa169
20. Hajdarevic R, Lande A, Mehlsen J, et al. Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci. Brain Behav Immun. May 2022;102:362-369. doi:10.1016/j.bbi.2022.03.010
21. Das S, Taylor K, Kozubek J, Sardell J, Gardner S. Genetic risk factors for ME/CFS identified using combinatorial analysis. J Transl Med. Dec 14 2022;20(1):598. doi:10.1186/s12967-022-03815-8
22. Cliff JM, King EC, Lee JS, et al. Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Immunol. 2019;10:796. doi:10.3389/fimmu.2019.00796
23. Klein J, Wood J, Jaycox J, et al. Distinguishing features of Long COVID identified through immune profiling. medRxiv. 2022:2022.08.09.22278592. doi:10.1101/2022.08.09.22278592
24. Yin K, Peluso MJ, Thomas R, et al. Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2. bioRxiv. Feb 10 2023;doi:10.1101/2023.02.09.527892
25. Ryan FJ, Hope CM, Masavuli MG, et al. Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection. BMC Med. Jan 14 2022;20(1):26. doi:10.1186/s12916-021-02228-6
26. Landay AL, Jessop C, Lennette ET, Levy JA. Chronic fatigue syndrome: clinical condition associated with immune activation. Lancet. Sep 21 1991;338(8769):707-12. doi:10.1016/0140-6736(91)91440-6
27. Komaroff AL. Is human herpesvirus-6 a trigger for chronic fatigue syndrome? J Clin Virol. Dec 2006;37 Suppl 1:S39-46. doi:10.1016/s1386-6532(06)70010-5
28. Komaroff AL, Buchwald DS. Chronic fatigue syndrome: an update. Annu Rev Med. 1998;49:1-13. doi:10.1146/annurev.med.49.1.1
29. Proal AD, VanElzakker MB. Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms. Front Microbiol. 2021;12:698169. doi:10.3389/fmicb.2021.698169
30. See DM, Tilles JG. alpha-Interferon treatment of patients with chronic fatigue syndrome. Immunol Invest. Jan-Mar 1996;25(1-2):153-64. doi:10.3109/08820139609059298
31. Masuda A, Nozoe SI, Matsuyama T, Tanaka H. Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome. Psychosom Med. Nov-Dec 1994;56(6):512-8. doi:10.1097/00006842-199411000-00006
32. Chang CM, Warren JL, Engels EA. Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults. Cancer. Dec 1 2012;118(23):5929-36. doi:10.1002/cncr.27612
33. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue S, Board on the Health of Select P, Institute of M. The National Academies Collection: Reports funded by National Institutes of Health. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. National Academies Press (US)
Copyright 2015 by the National Academy of Sciences. All rights reserved.; 2015.
34. Brenu EW, van Driel ML, Staines DR, et al. Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Transl Med. May 28 2011;9:81. doi:10.1186/1479-5876-9-81
10.1186/1479-5876-9-81.
35. Maher KJ, Klimas NG, Fletcher MA. Chronic fatigue syndrome is associated with diminished intracellular perforin. Clin Exp Immunol. Dec 2005;142(3):505-11. doi:10.1111/j.1365-2249.2005.02935.x
36. Brenu EW, Staines DR, Baskurt OK, et al. Immune and hemorheological changes in chronic fatigue syndrome. J Transl Med. Jan 11 2010;8:1. doi:10.1186/1479-5876-8-1
37. Osińska I, Popko K, Demkow U. Perforin: an important player in immune response. Cent Eur J Immunol. 2014;39(1):109-15. doi:10.5114/ceji.2014.42135
38. Huth TK, Staines D, Marshall-Gradisnik S. ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56 dim CD16+ and CD56 bright CD16 dim/- natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. J Transl Med. Apr 21 2016;14:97. doi:10.1186/s12967-016-0859-z
39. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. May 2008;9(5):503-10. doi:10.1038/ni1582
40. Gianchecchi E, Delfino DV, Fierabracci A. Natural Killer Cells: Potential Biomarkers and Therapeutic Target in Autoimmune Diseases? Front Immunol. 2021;12:616853. doi:10.3389/fimmu.2021.616853
41. Natelson BH, Brunjes DL, Mancini D. Chronic Fatigue Syndrome and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. Sep 7 2021;78(10):1056-1067. doi:10.1016/j.jacc.2021.06.045
42. Bozzini S, Albergati A, Capelli E, et al. Cardiovascular characteristics of chronic fatigue syndrome. Biomed Rep. Jan 2018;8(1):26-30. doi:10.3892/br.2017.1024
43. Wirth K, Scheibenbogen C. A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors. Autoimmun Rev. Jun 2020;19(6):102527. doi:10.1016/j.autrev.2020.102527
44. Fletcher MA, Zeng XR, Maher K, et al. Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26. PLoS One. May 25 2010;5(5):e10817. doi:10.1371/journal.pone.0010817
45. Curriu M, Carrillo J, Massanella M, et al. Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. Mar 20 2013;11:68. doi:10.1186/1479-5876-11-68
46. Tirelli U, Marotta G, Improta S, Pinto A. Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol. Dec 1994;40(6):601-8. doi:10.1111/j.1365-3083.1994.tb03511.x
47. Ford B, A. Bradley, and A. Bansal. Altered functional T cell subset populations and cytokine profile in patients with chronic fatigue syndrome: A pilot study. Journal of Chronic Diseases and Managment. 2016;1(1):1-9.
48. Bradley AS, Ford B, Bansal AS. Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls. Clin Exp Immunol. Apr 2013;172(1):73-80. doi:10.1111/cei.12043
49. Helliwell AM, Stockwell PA, Edgar CD, Chatterjee A, Tate WP. Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci. Oct 6 2022;23(19)doi:10.3390/ijms231911852
50. Tate WP, Walker MOM, Peppercorn K, Blair ALH, Edgar CD. Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID. Int J Mol Sci. 2023;24(6):5124.
51. Glynne P, Tahmasebi N, Gant V, Gupta R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med. Jan 2022;70(1):61-67. doi:10.1136/jim-2021-002051
52. Jubel JM, Barbati ZR, Burger C, Wirtz DC, Schildberg FA. The Role of PD-1 in Acute and Chronic Infection. Front Immunol. 2020;11:487. doi:10.3389/fimmu.2020.00487
53. Mandarano AH, Maya J, Giloteaux L, et al. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. Mar 2 2020;130(3):1491-1505. doi:10.1172/JCI132185
10.1172/JCI132185.
54. Booth NE, Myhill S, McLaren-Howard J. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med. 2012;5(3):208-20.
55. Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2(1):1-16.
56. Silvestre-Roig C, Fridlender ZG, Glogauer M, Scapini P. Neutrophil Diversity in Health and Disease. Trends Immunol. Jul 2019;40(7):565-583. doi:10.1016/j.it.2019.04.012
57. Nguyen T, Staines D, Johnston S, Marshall-Gradisnik S. Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/ chronic fatigue syndrome patients: A preliminary investigation. Asian Pac J Allergy Immunol. Jun 2019;37(2):102-108. doi:10.12932/ap-011117-0188
58. Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P. Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome. PLoS One. 2018;13(2):e0192817. doi:10.1371/journal.pone.0192817
59. Jahanbani F, Maynard RD, Sing JC, et al. Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study. PLoS One. 2022;17(8):e0272703. doi:10.1371/journal.pone.0272703
60. Komaroff AL. Inflammation correlates with symptoms in chronic fatigue syndrome. Proc Natl Acad Sci U S A. Aug 22 2017;114(34):8914-8916. doi:10.1073/pnas.1712475114
61. Montoya JG, Holmes TH, Anderson JN, et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci U S A. Aug 22 2017;114(34):E7150-E7158. doi:10.1073/pnas.1710519114
10.1073/pnas.1710519114. Epub 2017 Jul 31.
62. VanElzakker MB, Brumfield SA, Lara Mejia PS. Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods. Front Neurol. 2018;9:1033. doi:10.3389/fneur.2018.01033
63. Visser J, Graffelman W, Blauw B, et al. LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. J Neuroimmunol. Oct 1 2001;119(2):343-9. doi:10.1016/s0165-5728(01)00400-3
64. Long D, Chen Y, Wu H, Zhao M, Lu Q. Clinical significance and immunobiology of IL-21 in autoimmunity. J Autoimmun. May 2019;99:1-14. doi:10.1016/j.jaut.2019.01.013
65. Wang Q, Liu J. Regulation and Immune Function of IL-27. Adv Exp Med Biol. 2016;941:191-211. doi:10.1007/978-94-024-0921-5_9
66. Komai T, Inoue M, Okamura T, et al. Transforming Growth Factor-β and Interleukin-10 Synergistically Regulate Humoral Immunity via Modulating Metabolic Signals. Front Immunol. 2018;9:1364. doi:10.3389/fimmu.2018.01364
67. Liao W, Lin JX, Leonard WJ. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol. Oct 2011;23(5):598-604. doi:10.1016/j.coi.2011.08.003
68. Gadani SP, Cronk JC, Norris GT, Kipnis J. IL-4 in the brain: a cytokine to remember. J Immunol. Nov 1 2012;189(9):4213-9. doi:10.4049/jimmunol.1202246
69. Stringer EA, Baker KS, Carroll IR, et al. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. J Transl Med. Apr 9 2013;11:93. doi:10.1186/1479-5876-11-93
70. Taylor EB. The complex role of adipokines in obesity, inflammation, and autoimmunity. Clin Sci (Lond). Mar 26 2021;135(6):731-752. doi:10.1042/cs20200895
71. Hornig M, Montoya JG, Klimas NG, et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Sci Adv. Feb 2015;1(1)doi:10.1126/sciadv.1400121
72. Kavyani B, Lidbury BA, Schloeffel R, et al. Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle? Cell Mol Life Sci. Jul 11 2022;79(8):412. doi:10.1007/s00018-022-04380-5
73. Phetsouphanh C, Darley DR, Wilson DB, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. Feb 2022;23(2):210-216. doi:10.1038/s41590-021-01113-x
74. Schultheiß C, Willscher E, Paschold L, et al. The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. Cell Rep Med. Jun 21 2022;3(6):100663. doi:10.1016/j.xcrm.2022.100663
75. Queiroz MAF, Neves P, Lima SS, et al. Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome. Front Cell Infect Microbiol. 2022;12:922422. doi:10.3389/fcimb.2022.922422
76. Williams ES, Martins TB, Shah KS, et al. Cytokine Deficiencies in Patients with Long-COVID. J Clin Cell Immunol. 2022;13(6)
77. Low RN, Low RJ, Akrami A. A review of cytokine-based pathophysiology of Long COVID symptoms. Front Med (Lausanne). 2023;10:1011936. doi:10.3389/fmed.2023.1011936
78. Bekkering S, Domínguez-Andrés J, Joosten LAB, Riksen NP, Netea MG. Trained Immunity: Reprogramming Innate Immunity in Health and Disease. Annu Rev Immunol. Apr 26 2021;39:667-693. doi:10.1146/annurev-immunol-102119-073855
79. Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. Mar 2009;23(3):327-37. doi:10.1016/j.bbi.2008.11.005
80. Sumida T, Tsuboi H, Iizuka M, Asashima H, Matsumoto I. Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren's syndrome. Mod Rheumatol. Sep 2013;23(5):841-5. doi:10.1007/s10165-012-0788-5
81. Wallukat G, Schimke I. Agonistic autoantibodies directed against G-protein-coupled receptors and their relationship to cardiovascular diseases. Semin Immunopathol. May 2014;36(3):351-63. doi:10.1007/s00281-014-0425-9
82. Li J, Zhang Q, Liao Y, Zhang C, Hao H, Du J. The value of acetylcholine receptor antibody in children with postural tachycardia syndrome. Pediatr Cardiol. Jan 2015;36(1):165-70. doi:10.1007/s00246-014-0981-8
83. Loebel M, Grabowski P, Heidecke H, et al. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. Brain Behav Immun. Feb 2016;52:32-39. doi:10.1016/j.bbi.2015.09.013
84. Sur LM, Floca E, Sur DG, Colceriu MC, Samasca G, Sur G. Antinuclear Antibodies: Marker of Diagnosis and Evolution in Autoimmune Diseases. Lab Med. Jul 5 2018;49(3):e62-e73. doi:10.1093/labmed/lmy024
85. Slota C, Shi A, Chen G, Bevans M, Weng NP. Norepinephrine preferentially modulates memory CD8 T cell function inducing inflammatory cytokine production and reducing proliferation in response to activation. Brain Behav Immun. May 2015;46:168-79. doi:10.1016/j.bbi.2015.01.015
86. Sweetman E, Kleffmann T, Edgar C, de Lange M, Vallings R, Tate W. A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction. J Transl Med. Sep 24 2020;18(1):365. doi:10.1186/s12967-020-02533-3
87. Faraz A, Luyen Tien V, Hongya Z, et al. Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation. bioRxiv. 2022:2022.10.13.512091. doi:10.1101/2022.10.13.512091
88. Van Booven DJ, Gamer J, Joseph A, et al. Stress-Induced Transcriptomic Changes in Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Reveal Disrupted Immune Signatures. Int J Mol Sci. Jan 31 2023;24(3)doi:10.3390/ijms24032698
89. Sweetman E, Ryan M, Edgar C, MacKay A, Vallings R, Tate W. Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome. Int J Immunopathol Pharmacol. Jan-Dec 2019;33:2058738418820402. doi:10.1177/2058738418820402
90. Fernandez-Guerra P, Gonzalez-Ebsen AC, Boonen SE, et al. Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study. Biomolecules. Jun 29 2021;11(7)doi:10.3390/biom11070961
91. Germain A, Levine SM, Hanson MR. In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling. Proteomes. Jan 29 2021;9(1)doi:10.3390/proteomes9010006
92. Helliwell AM, Sweetman EC, Stockwell PA, Edgar CD, Chatterjee A, Tate WP. Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions. Clin Epigenetics. Nov 4 2020;12(1):167. doi:10.1186/s13148-020-00960-z
93. de Vega WC, Vernon SD, McGowan PO. DNA methylation modifications associated with chronic fatigue syndrome. PLoS One. 2014;9(8):e104757. doi:10.1371/journal.pone.0104757
94. de Vega WC, McGowan PO. The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome: deciphering complex phenotypes. Epigenomics. Nov 2017;9(11):1337-1340. doi:10.2217/epi-2017-0106
95. Herrera S, de Vega WC, Ashbrook D, Vernon SD, McGowan PO. Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Epigenetics. 2018;13(12):1174-1190. doi:10.1080/15592294.2018.1549769
96. Brenu EWS, D.R.; Marshall-Gradisnik S.M. . Methylation Profile of CD4+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Clin Cell Immunol. 2014;5(228)
97. Trivedi MS, Oltra E, Sarria L, et al. Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns. PLoS One. 2018;13(7):e0201066. doi:10.1371/journal.pone.0201066
98. de Vega WC, Erdman L, Vernon SD, Goldenberg A, McGowan PO. Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome. Epigenomics. May 2018;10(5):539-557. doi:10.2217/epi-2017-0150
99. Nguyen T, Johnston S, Clarke L, Smith P, Staines D, Marshall-Gradisnik S. Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels. Clin Exp Immunol. Feb 2017;187(2):284-293. doi:10.1111/cei.12882
100. Held K, Tóth BI. TRPM3 in Brain (Patho)Physiology. Front Cell Dev Biol. 2021;9:635659. doi:10.3389/fcell.2021.635659
101. Vriens J, Owsianik G, Hofmann T, et al. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron. May 12 2011;70(3):482-94. doi:10.1016/j.neuron.2011.02.051
102. Cabanas H, Muraki K, Staines D, Marshall-Gradisnik S. Naltrexone Restores Impaired Transient Receptor Potential Melastatin 3 Ion Channel Function in Natural Killer Cells From Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Front Immunol. 2019;10:2545. doi:10.3389/fimmu.2019.02545
103. Nguyen T, Staines D, Nilius B, Smith P, Marshall-Gradisnik S. Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients. Biol Res. May 31 2016;49(1):27. doi:10.1186/s40659-016-0087-2
104. Cabanas H, Muraki K, Eaton N, Balinas C, Staines D, Marshall-Gradisnik S. Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. Mol Med. Aug 14 2018;24(1):44. doi:10.1186/s10020-018-0046-1
105. Marshall-Gradisnik S, Huth T, Chacko A, Johnston S, Smith P, Staines D. Natural killer cells and single nucleotide polymorphisms of specific ion channels and receptor genes in myalgic encephalomyelitis/chronic fatigue syndrome. Appl Clin Genet. 2016;9:39-47. doi:10.2147/tacg.S99405
106. Dembla S, Behrendt M, Mohr F, et al. Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels. Elife. Aug 15 2017;6doi:10.7554/eLife.26280
107. Singh DS, A. . Naltrexone. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK534811
108. Weinstock L. EFFICACY OF LOW DOSE NALTREXONE IN PATIENTS WITH CROHN’S COLITIS AND ILEITIS. Inflammatory Bowel Diseases. 2022;28(Supplement_1):S106-S107. doi:10.1093/ibd/izac015.172
109. Parker CE, Nguyen TM, Segal D, MacDonald JK, Chande N. Low dose naltrexone for induction of remission in Crohn's disease. Cochrane Database Syst Rev. Apr 1 2018;4(4):Cd010410. doi:10.1002/14651858.CD010410.pub3
110. Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. Feb 2013;65(2):529-38. doi:10.1002/art.37734
111. Cree BA, Kornyeyeva E, Goodin DS. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. Aug 2010;68(2):145-50. doi:10.1002/ana.22006
112. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. Apr 2014;33(4):451-9. doi:10.1007/s10067-014-2517-2
113. Mapunda JA, Tibar H, Regragui W, Engelhardt B. How Does the Immune System Enter the Brain? Front Immunol. 2022;13:805657. doi:10.3389/fimmu.2022.805657
114. Norris GT, Kipnis J. Immune cells and CNS physiology: Microglia and beyond. J Exp Med. Jan 7 2019;216(1):60-70. doi:10.1084/jem.20180199
115. Nakatomi Y, Mizuno K, Ishii A, et al. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An (1)(1)C-(R)-PK11195 PET Study. J Nucl Med. Jun 2014;55(6):945-50. doi:10.2967/jnumed.113.131045
116. Visser D, Golla SSV, Verfaillie SCJ, et al. Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET. medRxiv. 2022:2022.06.02.22275916. doi:10.1101/2022.06.02.22275916
117. Nelson T, Zhang LX, Guo H, Nacul L, Song X. Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings. Front Neurol. 2021;12:769511. doi:10.3389/fneur.2021.769511
118. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). Oct 2021;53(10):737-754. doi:10.1080/23744235.2021.1924397
119. Lull ME, Block ML. Microglial activation and chronic neurodegeneration. Neurotherapeutics. Oct 2010;7(4):354-65. doi:10.1016/j.nurt.2010.05.014
120. Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH. Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson's disease. J Neurosci. Nov 1 2001;21(21):8447-55. doi:10.1523/jneurosci.21-21-08447.2001
121. Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity. Oct 2005;23(4):344-6. doi:10.1016/j.immuni.2005.10.001
122. Pais TF, Figueiredo C, Peixoto R, Braz MH, Chatterjee S. Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway. J Neuroinflammation. Oct 9 2008;5:43. doi:10.1186/1742-2094-5-43
123. Tracey KJ. The inflammatory reflex. Nature. Dec 19-26 2002;420(6917):853-9. doi:10.1038/nature01321
124. Mackay A, Tate WP. A compromised paraventricular nucleus within a dysfunctional hypothalamus: A novel neuroinflammatory paradigm for ME/CFS. International Journal of Immunopathology and Pharmacology. 2018;32:2058738418812342. doi:10.1177/2058738418812342
125. Mackay A. A Paradigm for Post-Covid-19 Fatigue Syndrome Analogous to ME/CFS. Hypothesis and Theory. Frontiers in Neurology. 2021-August-02 2021;12doi:10.3389/fneur.2021.701419
126. Bested AC, Saunders PR, Logan AC. Chronic fatigue syndrome: neurological findings may be related to blood–brain barrier permeability. Medical Hypotheses. 2001/08/01/ 2001;57(2):231-237. doi:https://doi.org/10.1054/mehy.2001.1306
127. Kamimura D, Ohki T, Arima Y, Murakami M. Gateway reflex: neural activation-mediated immune cell gateways in the central nervous system. Int Immunol. Jun 26 2018;30(7):281-289. doi:10.1093/intimm/dxy034
128. Sabharwal L, Kamimura D, Meng J, et al. The Gateway Reflex, which is mediated by the inflammation amplifier, directs pathogenic immune cells into the CNS. J Biochem. Dec 2014;156(6):299-304. doi:10.1093/jb/mvu057
129. Gate D, Tapp E, Leventhal O, et al. CD4(+) T cells contribute to neurodegeneration in Lewy body dementia. Science. Nov 12 2021;374(6569):868-874. doi:10.1126/science.abf7266
130. Sampson TR, Debelius JW, Thron T, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. Dec 1 2016;167(6):1469-1480 e12. doi:10.1016/j.cell.2016.11.018
131. Schroeder BO, Backhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. Oct 2016;22(10):1079-1089. doi:10.1038/nm.4185
132. König RS, Albrich WC, Kahlert CR, et al. The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Front Immunol. 2021;12:628741. doi:10.3389/fimmu.2021.628741
133. Ariza ME. Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: The Human Herpesviruses Are Back! Biomolecules. 2021;11(2). doi:10.3390/biom11020185
134. Williams Ph DM, Cox B, Lafuse Ph DW, Ariza ME. Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clin Ther. May 2019;41(5):848-863. doi:10.1016/j.clinthera.2019.04.009
135. Wessely S. Chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. Aug 1991;54(8):669-71. doi:10.1136/jnnp.54.8.669
136. Vink M, Vink-Niese A. Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review. Health Psychol Open. Jan-Jun 2019;6(1):2055102919840614. doi:10.1177/2055102919840614
137. Vink M, Vink-Niese A. The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Diseases. Jan 16 2023;11(1)doi:10.3390/diseases11010011
138. Shepherd CB. PACE trial claims for recovery in myalgic encephalomyelitis/chronic fatigue syndrome - true or false? It's time for an independent review of the methodology and results. J Health Psychol. Aug 2017;22(9):1187-1191. doi:10.1177/1359105317703786
139. Hodges L, Nielsen T, Cochrane D, Baken D. The physiological time line of post-exertional malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). TRANSLATIONAL SPORTS MEDICINE. 2020;3(3):243-249. doi:https://doi.org/10.1002/tsm2.133
140. Rekeland IG, Fosså A, Lande A, et al. Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study. Front Med (Lausanne). 2020;7:162. doi:10.3389/fmed.2020.00162
141. Bolton MJ, Chapman BP, Van Marwijk H. Low-dose naltrexone as a treatment for chronic fatigue syndrome. BMJ Case Rep. Jan 6 2020;13(1)doi:10.1136/bcr-2019-232502
142. Welsh RM. Natural killer cells and interferon. Crit Rev Immunol. 1984;5(1):55-93.
143. Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. Am J Med. Nov 1990;89(5):561-8. doi:10.1016/0002 9343(90)90173-b
144. Peterson PK, Shepard J, Macres M, et al. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med. Nov 1990;89(5):554-60. doi:10.1016/0002-9343(90)90172-a
145. Rowe KS. Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents. J Psychiatr Res. Jan-Feb 1997;31(1):133-47. doi:10.1016/s0022-3956(96)00047-7
146. Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, et al. Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome. Am J Med. Jul 1997;103(1):38-43. doi:10.1016/s0002-9343(97)90045-0
147. Glazachev OS, Dudnik Е N, Zagaynaya EE. [Pharmacological treatment of patients with chronic fatigue syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(4):40-44. Medikamentoznaia terapiia patsientov s sindromom khronicheskoĭ ustalosti. doi:10.17116/jnevro20171174140-44
148. Park SB, Kim KN, Sung E, Lee SY, Shin HC. Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study. Biol Pharm Bull. May 1 2016;39(5):674-9. doi:10.1248/bpb.b15-00623
149. Montoya JG, Kogelnik AM, Bhangoo M, et al. Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J Med Virol. Dec 2013;85(12):2101-9. doi:10.1002/jmv.23713
150. Wood E, Hall KH, Tate W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 'long-haulers'? Chronic Dis Transl Med. Mar 2021;7(1):14-26. doi:10.1016/j.cdtm.2020.11.002
151. Lebedeva AV, Shchukin IA, Soldatov MA, et al. [Asthenia, emotional disorders and quality of life of patients with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(10 Pt 2):99-104. Asteniia, émotsional'nye rasstroĭstva i kachestvo zhizni u patsientov s rasseiannym sklerozom.
152. Tereshin AE, Kiryanova VV, Reshetnik DA. Correction of Mitochondrial Dysfunction in the Complex Rehabilitation of COVID-19 Patients. Neurosci Behav Physiol. 2022;52(4):511-514. doi:10.1007/s11055-022-01269-5
153. Ozel O, Vaughn CB, Eckert SP, Jakimovski D, Lizarraga AA, Weinstock-Guttman B. Dimethyl Fumarate in the Treatment of Relapsing-Remitting Multiple Sclerosis: Patient Reported Outcomes and Perspectives. Patient Relat Outcome Meas. 2019;10:373-384. doi:10.2147/prom.S168095
154. Ortiz JF, Khan SA, Salem A, Lin Z, Iqbal Z, Jahan N. Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug. Cureus. Oct 6 2020;12(10):e10818. doi:10.7759/cureus.10818
155. Cash A, Kaufman DL. Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial. J Transl Med. Jun 28 2022;20(1):295. doi:10.1186/s12967-022-03488-3
156. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. Mar 19 2009;1(1):6. doi:10.1186/1757-4749-1-6
157. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. Jan 26 2009;8:4. doi:10.1186/1475-2891-8-4
158. Venturini L, Bacchi S, Capelli E, Lorusso L, Ricevuti G, Cusa C. Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study. Oxid Med Cell Longev. 2019;2019:1684198. doi:10.1155/2019/1684198
159. Groeger D, O'Mahony L, Murphy EF, et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. Jul-Aug 2013;4(4):325-39. doi:10.4161/gmic.25487
160. Borody TJ, Nowak A, Finlayson S. The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy. Other Journal Article. Journal of the Australasian College of Nutritional and Environmental Medicine. 2012;31(3):3-8.
161. Kenyon JN, Coe S, Izadi H. A retrospective outcome study of 42 patients with Chronic Fatigue Syndrome, 30 of whom had Irritable Bowel Syndrome. Half were treated with oral approaches, and half were treated with Faecal Microbiome Transplantation. Human Microbiome Journal. 2019/08/01/ 2019;13:100061. doi:https://doi.org/10.1016/j.humic.2019.100061
162. Fluge Ø, Bruland O, Risa K, et al. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One. 2011;6(10):e26358. doi:10.1371/journal.pone.0026358
163. Fluge Ø, Rekeland IG, Lien K, et al. B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. May 7 2019;170(9):585-593. doi:10.7326/m18-1451
164. Park SB, Kim K-N, Sung E, Lee SY, Shin HC. Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study. Biological and Pharmaceutical Bulletin. 2016;39(5):674-679. doi:10.1248/bpb.b15-00623
165. McInnes IB, Gravallese EM. Immune-mediated inflammatory disease therapeutics: past, present and future. Nat Rev Immunol. Oct 2021;21(10):680-686. doi:10.1038/s41577-021-00603-1
166. Brownlie H, Speight N. Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare (Basel). Nov 12 2021;9(11)doi:10.3390/healthcare9111546
167. Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520. doi:10.3389/fimmu.2014.00520
168. Anthony RM, Nimmerjahn F. The role of differential IgG glycosylation in the interaction of antibodies with FcγRs in vivo. Curr Opin Organ Transplant. Feb 2011;16(1):7-14. doi:10.1097/MOT.0b013e328342538f
169. Leusen JHW, Nimmerjahn F. The Role of IgG in Immune Responses. In: Nimmerjahn F, ed. Molecular and Cellular Mechanisms of Antibody Activity. Springer New York; 2013:85-112.
170. Aalberse R. The role of IgG antibodies in allergy and immunotherapy. Allergy. Jul 2011;66 Suppl 95:28-30. doi:10.1111/j.1398-9995.2011.02628.x
171. Fillatreau S. B cells and their cytokine activities implications in human diseases. Clin Immunol. Jan 2018;186:26-31. doi:10.1016/j.clim.2017.07.020
172. Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. Feb 14 2008;358(7):676-88. doi:10.1056/NEJMoa0706383
173. Scher JU. B-cell therapies for rheumatoid arthritis. Bull NYU Hosp Jt Dis. 2012;70(3):200-3.
174. Sotzny F, Blanco J, Capelli E, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease. Autoimmun Rev. Jun 2018;17(6):601-609. doi:10.1016/j.autrev.2018.01.009
175. Behan WM, More IA, Behan PO. Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol. 1991;83(1):61-5. doi:10.1007/bf00294431
176. Missailidis D, Annesley SJ, Allan CY, et al. An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients. Int J Mol Sci. Feb 6 2020;21(3)doi:10.3390/ijms21031074
177. Castro-Marrero J, Cordero MD, Sáez-Francas N, et al. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. Nov 20 2013;19(15):1855-60. doi:10.1089/ars.2013.5346
178. Cordero MD, de Miguel M, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AM. Oxidative stress and mitochondrial dysfunction in fibromyalgia. Neuro Endocrinol Lett. 2010;31(2):169-73.
179. Castro-Marrero J, Domingo JC, Cordobilla B, et al. Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. Apr 2022;36(10-12):729-739. doi:10.1089/ars.2022.0018
180. Gueven N, Ravishankar P, Eri R, Rybalka E. Idebenone: When an antioxidant is not an antioxidant. Redox Biol. Jan 2021;38:101812. doi:10.1016/j.redox.2020.101812
181. Paul BD, Lemle MD, Komaroff AL, Snyder SH. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. Aug 24 2021;118(34)doi:10.1073/pnas.2024358118
182. Walker MOM, Hall KH, Peppercorn K, Tate WP. The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medical Research Archives. 2022;10(9)
183. Gareau MG, Barrett KE. Role of the microbiota-gut-brain axis in postacute COVID syndrome. Am J Physiol Gastrointest Liver Physiol. Apr 1 2023;324(4):G322-g328. doi:10.1152/ajpgi.00293.2022
184. Mullish BH, Quraishi MN, Segal JP, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut. Nov 2018;67(11):1920-1941. doi:10.1136/gutjnl-2018-316818