A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune-related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest. This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the “infectious” trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting

Longitudinal Monitoring of SARS-CoV-2 IgM and IgG Seropositivity to Detect COVID-19.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel beta-coronavirus that has recently emerged as the cause of the 2019 coronavirus pandemic (COVID-19). Polymerase chain reaction (PCR) based tests are optimal and recommended for the diagnosis of an acute SARS-CoV-2 infection. Serology tests for viral antibodies provide an important tool to diagnose previous exposure to the virus. Here we evaluate the analytical performance parameters of the Diazyme SARS-CoV-2 IgM/IgG serology assays and describe the kinetics of IgM and IgG seroconversion observed in patients with PCR-confirmed COVID-19 who were admitted to our hospital.MethodsWe validated the performance of the Diazyme assay in 235 presumed SARS-CoV-2 negative subjects to determine specificity. Subsequently, we evaluated the SARS-CoV-2 IgM and IgG seroconversion of 54 PCR-confirmed COVID-19 patients and determined sensitivity of the assay at three different timeframes.ResultSensitivity and specificity for detecting seropositivity at ≥15 days following a positive SARS-CoV-2 PCR result, was 100.0% and 98.7% when assaying for the panel of IgM and IgG. The median time to seropositivity observed for a reactive IgM and IgG result from the date of a positive PCR was 5 days (IQR: 2.75-9 days) and 4 days (IQR: 2.75-6.75 days), respectively.ConclusionsOur data demonstrate that the Diazyme IgM/IgG assays are suited for the purpose of detecting SARS-CoV-2 IgG and IgM in patients with suspected SARS-CoV-2 infections. For the first time, we report longitudinal data showing the evolution of seroconversion for both IgG and IgM in a cohort of acutely ill patients in the United States. We also demonstrate a low false positive rate in patients who were presumed to be disease free

An unusual presentation of a case of human psittacosis

Background: Chlamydia psittaci is a gram-negative, obligate intracellular organism. Birds are the main reservoir, but also non-avian domestic animals and humans can be infected. In humans it mostly causes respiratory infections due to occupational exposure with varying severity. Sensitive and specific diagnostic tests are needed to define psittacosis in humans as these tests also allow rapid tracing of the animal source. However, diagnosis in humans is often based on time-consuming culture techniques and antibody detection assays as in many countries, the existing molecular diagnostic tests for psittacosis are not reimbursed by the public health insurance. Case presentation: An 82-year old female was referred to the hospital with a non-productive cough since four weeks and since one week fever up to 39 degrees C, myalgia, generalized skin rash, acral edema and generalized weakness under treatment with moxifloxacin. Blood analysis showed signs of inflammation with mild eosinophilia. Chest CT showed multiple peripheral ground glass opacities with consolidation in both lungs. Pulmonary function testing only showed a mild decrease in diffusion capacity. Viral and bacterial serology were negative. As the patient kept a pet parakeet for over ten years, a nested PCR for C. psittaci was performed on a nasopharyngeal swab of the patient and on feces of the parakeet. Both returned positive for the same genotype. Genotyping was performed by a genotype-specific real-time PCR. The patient fully recovered after a ten-day course of azithromycin. Conclusion: Due to non-specific signs during psittacosis, early detection of the infection and differentiation from hypersensitivity pneumonitis can be challenging. Culture and antibody titers for C. psittaci have a lower sensitivity than PCR-testing due to several factors. We present a case of human psittacosis (presenting as pneumonia) with diagnosis based on clinical findings confirmed by means of nested PCR. This case suggests the added value of PCR in suspect cases despite negative serology. Our current paper underlines the need for a broader implementation of PCR for early diagnosis of human psittacosis and thus early initiation of correct antibiotic treatment with reduction of morbidity and mortality

A gene signature for post-infectious chronic fatigue syndrome

Background: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment

Viral Encephalitis: Etiology, Clinical Features, Diagnosis and Management

8openSergio Ferrari; Antonio Toniolo; Salvatore Monaco; Filippo Luciani; Francesca Cainelli; Andreina Baj; Zelalem Temesgen; Sandro VentoSergio, Ferrari; Toniolo, Antonio; Salvatore, Monaco; Filippo, Luciani; Francesca, Cainelli; Baj, Andreina; Zelalem, Temesgen; Sandro, Vent

Fatigue in patients with inflammatory bowel disease is associated with distinct differences in immune parameters

Background: Although it is well recognized that fatigue is an important problem in many of the quiescent inflammatory bowel disease (IBD) patients, it is unknown whether the immune status is different in fatigued versus non-fatigued patients. In this study, we contrasted various characteristics of the immune system in fatigued against non-fatigued patients with IBD in clinical remission. Patients and methods: Patients with IBD in clinical remission were phenotyped according to the Montreal classification, and the checklist individual strength-fatigue (CIS-fatigue) was used to assess fatigue (CIS-fatigue ≥ 35). Flow cytometry on peripheral blood samples was used to investigate differences in leukocyte subsets. The expression of various cytokines was determined in stimulated whole blood and serum samples using enzyme-linked immunosorbent assay. Differences between fatigued and non-fatigued patients with IBD were assessed. Results: In total, 55 patients were included in the fatigue group (FG) and 29 patients in the non-fatigue group (NFG). No differences in demographic and clinical characteristics were observed between the groups. Flow cytometry data showed a significantly lower percentage of monocytes (p = 0.011) and a higher percentage of memory T-cells (p = 0.005) and neutrophils (p = 0.033) in the FG compared with the NFG. Whole blood stimulation showed increased TNF-α (p = 0.022) and IFN-γ (p = 0.047) in the FG. The median serum level was significantly higher for IL-12 (p < 0.001) and IL-10 (p = 0.005) and lower for IL-6 (p = 0.002) in the FG compared with NFG. Conclusion: Significant differences in immune profile between fatigued and non-fatigued patients with IBD in clinical remission wer