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3 Common Mechanistic Factors of Infection-Associated Chronic Illnesses
Pages 17-36

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From page 17...
... (Chertow) • In animal model studies, Lyme disease bacteria can persist follow ing conventional single antibiotic treatments, and combination treatments were more effective in clearing infection in some mod els.
From page 18...
... as a major problem in younger patients. Echoing comments from Anthony Komaroff, Harvard Medical School, on the overlap between diseases, she found through a prospective observational study that about 50 percent of long COVID patients fit the diagnostic criteria for ME/CFS (Kedor et al., 2022)
From page 19...
... But under certain conditions, EBV can reactivate and enter a lytic cycle, where the virus expresses all its genes to produce infectious viral particles, leading to cell death and viral propagation. The immune response to EBV is complex, but Peluso highlighted that antibody levels can be measured as a proxy for viral activity, with some antibodies persisting over time and others peaking and waning after a period of months.
From page 20...
... developing multiple sclerosis (MS) , Peluso stated.3 Other herpesviruses have been frequently associated with ME/CFS, but the current evidence in literature is insufficient to firmly establish whether EBV infection is associated with developing ME/CFS, or whether the chronic illness is creating an environment where EBV can reactivate.
From page 21...
... . Another potential explanation could point to the immunoregulatory effects that CMV exerts on its host that alter immune responses that would otherwise drive development of long COVID.
From page 22...
... Autonomic Dysfunction Satish Raj, University of Calgary, spoke about the cardiovascular aspects of autonomic dysfunction and its downstream effects, including postural orthostatic tachycardia syndrome (POTS) and orthostatic intolerance.
From page 23...
... Nonpharmaceutical approaches can include increased dietary salt intake, diet changes, compression garments, and exercise as tolerated. A recent study found that a high salt diet increased blood volume, decreased norepinephrine levels, and decreased the patient's heart rate (Garland et al., 2021)
From page 24...
... Involvement of autonomic dysfunction in ME/CFS has been long known, with reduced cerebral blood flow and hypocapnia detected in ME/CFS patients upon orthostatic challenge (van Campen et al., 2020)
From page 25...
... . In addition, this study recognized and adjusted the measured cerebral blood flow based on the extent of hypocapnia in the study population to reveal a greater severity in cerebral blood flow reduction for the long COVID cohort compared with the POTS group.7 Miglis contended that inclusion of cerebral blood flow and end-tidal CO2 measurements are an important protocol adjustment that could be included in future studies, as screening for only blood pressure and heart rate may underdiagnose or overlook infection-associated dysautonomia disorders.
From page 26...
... . Many patients reported adverse effects of depression, anxiety, problems with memory and concentrations, and a variety of neurovegetative symptoms including fatigue and appetite alterations.
From page 27...
... Using the same experimental setup, Miller described the finding that fMRI detected reduced neural activation in the basal ganglia that correlated with higher fatigue levels in ME/ CFS patients. He explained that, based on data from animal studies where treatment with IFNα suppressed dopamine release, dopamine dysregulation is a likely mechanism underlying the symptoms in humans.
From page 28...
... 28 A RESEARCH AGENDA IN INFECTION-ASSOCIATED CHRONIC ILLNESSES 4. Testing pharmacologic agents targeting antiviral and inflammatory cytokines and their signaling pathways as treatments for infection associated chronic illnesses.
From page 29...
... Acute infection can trigger ME/CFS symptoms, she said, which has been seen following Lyme disease and HIV. Additionally, prior research has also shown metabolomic irregularities and immune dysregulation in ME/CFS, and there has been anecdotal success with fecal microbiota transplantation for ME/ CFS patients.
From page 30...
... Building from previous discussions, Robinson posed an overarching question of whether EBV is a causal contributor to these autoimmune diseases or whether it is just an epidemiological phenomenon. A recent longitudinal analysis reveals a high prevalence of EBV associated with MS, where 801 patients developed MS and 800 of them had prior EBV infection (Bjornevik et al., 2022)
From page 31...
... To summarize the data, Robinson said that this research demonstrates a critical role for EBNA-1-mediated molecular mimicry in driving the autoimmune response that potentially underlies the pathogenesis in approximately one-quarter of human MS patients. It is likely there are additional pathways through which activation of B cell and other immune cells contribute to molecular mimicry and other mechanisms that play a role in the pathogenesis of autoimmune diseases associated with EBV infection.
From page 32...
... Chertow summarized by noting that SARS-CoV-2 RNA can persist in multiple anatomic compartments for an extended interval and that SARS-CoV-2 can infect and replicate in multiple cell types outside of the respiratory tract. Lessons from Animal Studies Monica Embers, Tulane University, shared her work on Lyme disease.
From page 33...
... for Bartonella, Babesia, and B burgdorferi were negative.11 Despite extended retreatment with antibiotics, the patient's neurocognitive and behavioral symptoms worsened and she eventually died 15 years after her initial Lyme disease diagnosis.
From page 34...
... Given the prevalence of both Lyme disease and COVID-19 in the United States and Europe, Embers suggested the possibility of these interacting as a syndemic. Discussion Several questions during the discussion were related to pathogen persistence in the human body.
From page 35...
... Even in mild or moderate cases, there is likely a meaningful inflammatory response, he said. The mechanisms of pathogen persistence and evasion of adaptive immune response is not well defined, said Chertow, calling for more research on mechanisms of persistence and immune evasion.
From page 36...
... Robinson replied that there is an EBV vaccine advancing through Phase 2 trials at NIH, and Moderna just initiated a set of trials as well, but both are focused on prevention of EBV infection, which may differ from the type of clearance of already infected cells that many are hoping for.


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