Abstract: “The prevalence of autoimmune diseases (ADs) worldwide has rapidly increased over the past few decades. Thus, in addition to the classical risk factors for ADs, such as genetic polymorphisms, infections and smoking, environmental triggers have been considered. Recent sequencing-based approaches have revealed that patients with extra-intestinal ADs, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. Faecal microbiota transplantation or inoculation with specific microbes in animal models of ADs support the hypothesis that alterations of gut microbiota influence autoimmune responses and disease outcome. Here, we describe the compositional and functional changes in the gut microbiota in patients with extra-intestinal AD and discuss how the gut microbiota affects immunity. Moreover, we examine how the gut microbiota might be modulated in patients with ADs as a potential preventive or therapeutic approach.”

Miyauchi E, Shimokawa C, Steimle A, Desai MS, Ohno H. The impact of the gut microbiome on extra-intestinal autoimmune diseases. Nat Rev Immunol. 2022 May 9. doi: 10.1038/s41577-022-00727-y. Epub ahead of print. PMID: 35534624.


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Abstract: “The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accelerates the discovery of prophylactic and therapeutic drugs for persons infected with the virus. Drug repurposing for the COVID-19 pandemic has received particular attention. Increasing clinical data suggest that antidepressant use in early-stage subjects with COVID-19 might be associated with a reduced risk of intubation or death. Among the antidepressants, fluvoxamine is the most attractive drug for mild to moderate subjects with COVID-19. In this article, we review the mechanisms of action (i.e., serotonin transporter, sigma-1 receptor, and acid sphingomyelinase) of fluvoxamine for COVID-19. Furthermore, we discuss a possible link between maternal COVID-19 infection and a risk for neuropsychiatric disorders (i.e., autism spectrum disorder and schizophrenia) in offspring.”

Hashimoto Y, Suzuki T, Hashimoto K. Mechanisms of action of fluvoxamine for COVID-19: a historical review. Mol Psychiatry. 2022 Jan 7:1–10. doi: 10.1038/s41380-021-01432-3. Epub ahead of print. PMID: 34997196; PMCID: PMC8739627.



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Abstract:  “Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.”

Brouwer, R.M., Klein, M., Grasby, K.L. et al. Genetic variants associated with longitudinal changes in brain structure across the lifespan. Nat Neurosci 25: 421–432 (2022). https://doi.org/10.1038/s41593-022-01042-4.



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Abstract: “Exposure to ambient air pollution is a well-established determinant of health and disease. The Lancet Commission on pollution and health concludes that air pollution is the leading environmental cause of global disease and premature death. Indeed, there is a growing body of evidence that links air pollution not only to adverse cardiorespiratory effects but also to increased risk of cerebrovascular and neuropsychiatric disorders. Despite being a relatively new area of investigation, overall, there is mounting recent evidence showing that exposure to multiple air pollutants, in particular to fine particles, may affect the central nervous system (CNS) and brain health, thereby contributing to increased risk of stroke, dementia, Parkinson’s disease, cognitive dysfunction, neurodevelopmental disorders, depression and other related conditions. The underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests inflammation and oxidative stress to be crucial factors in the pathogenesis of air pollution-induced disorders, driven by the enhanced production of proinflammatory mediators and reactive oxygen species in response to exposure to various air pollutants. From a public health perspective, mitigation measures are urgent to reduce the burden of disease and premature mortality from ambient air pollution.”

Hahad O, Lelieveld J, Birklein F, Lieb K, Daiber A, Münzel T. Ambient Air Pollution Increases the Risk of Cerebrovascular and Neuropsychiatric Disorders through Induction of Inflammation and Oxidative Stress. Int J Mol Sci. 2020 Jun 17;21(12):4306. doi: 10.3390/ijms21124306. PMID: 32560306; PMCID: PMC7352229.


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Abstract: “Lung infections and smoking are risk factors for multiple sclerosis, a T-cell-mediated autoimmune disease of the central nervous system. In addition, the lung serves as a niche for the disease-inducing T cells for long-term survival and for maturation into migration-competent effector T cells. Why the lung tissue in particular has such an important role in an autoimmune disease of the brain is not yet known. Here we detected a tight interconnection between the lung microbiota and the immune reactivity of the brain. A dysregulation in the lung microbiome significantly influenced the susceptibility of rats to developing autoimmune disease of the central nervous system. Shifting the microbiota towards lipopolysaccharide-enriched phyla by local treatment with neomycin induced a type-I-interferon-primed state in brain-resident microglial cells. Their responsiveness towards autoimmune-dominated stimulation by type II interferons was impaired, which led to decreased proinflammatory response, immune cell recruitment and clinical signs. Suppressing lipopolysaccharide-producing lung phyla with polymyxin B led to disease aggravation, whereas addition of lipopolysaccharide-enriched phyla or lipopolysaccharide recapitulated the neomycin effect. Our data demonstrate the existence of a lung–brain axis in which the pulmonary microbiome regulates the immune reactivity of the central nervous tissue and thereby influences its susceptibility to autoimmune disease development.”

Hosang, L., Canals, R.C., van der Flier, F.J. et al. The lung microbiome regulates brain autoimmunity. Nature 603 : 138–144 (2022). https://doi.org/10.1038/s41586-022-04427-4.


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Abstract: SARS-CoV-2 can cause acute respiratory distress and death in some patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD), leading to inflammatory death (pyroptosis) and release of potent inflammatory mediators. Here we show that about 6% of blood monocytes in COVID-19 patients  are infected with SARS-CoV-2. Monocyte infection depends on uptake of antibody-opsonized virus by Fcγ receptors. Vaccine recipient plasma does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.

Junqueira, C., Crespo, Â., Ranjbar, S. et al. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation. Nature (2022). https://doi.org/10.1038/s41586-022-04702-4


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Abstract:  The acute cerebral ischemia induced by the COVID-19 vaccine is one of the side effects. We report the first case of a patient who suffered from a neurological deficit mimicking a stroke after receiving his 1st dose of the inactivated COVID-19 vaccine BIBP (Sinopharm) and who mainly developed cerebral venous thrombosis. Our reported case is a 36-year-old man who was admitted to our intensive care unit 2 days after his first injection dose of the inactivated COVID-19 vaccine BIBP (Sinopharm). He presented a numbness in his left arm and legs with headaches 24 hours after the vaccine injection. In the second day, he had asymmetry of the face which was aggravated by the installation of disturbance of consciousness and a state of agitation. His vital signs were normal. A brain CT scan without injection was done showing a right deep parietal ischemic stroke. The treatment was initiated by aspirin. cerebral MRI showed a very extensive stroke ischemic in the superficial and deep right parietal territory with the onset of hemorrhagic rearrangement of the right basal ganglia, magnetic resonance imaging angiography of the supra-aortic trunks was normal. The patient gradually improved and was discharged after 15 days of his stay in the intensive care unit. The installation of ischemic stroke reported in our young patient after receiving his first dose of inactivated COVID-19 vaccine BIBP; could be a new immune response to the vaccine.

Elaidouni G, Chetouani Z, Manal Merbouh CB, Bkiyar H, Housni B. Acute ischemic stroke after first dose of inactivated COVID-19 vaccine: A case report. Radiol Case Rep. 2022 Apr 6;17(6):1942-1945. doi: 10.1016/j.radcr.2022.02.082. PMID: 35392049; PMCID: PMC8983275.


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Background: Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain.

Methods: In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics.

Results: EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients.

Conclusion: A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.

Meng M, Zhang S, Dong X, Sun W, Deng Y, Li W, Li R, Annane D, Wu Z, Chen D. COVID-19 associated EBV reactivation and effects of ganciclovir treatment. Immun Inflamm Dis. 2022 Apr;10(4):e597. doi: 10.1002/iid3.597. PMID: 35349757.


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Excerpt: “The human pancreas is a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Following SARS-CoV-2 infections, reduced numbers of insulin secretory granules in beta cells and impaired glucose-stimulated insulin secretion have been observed. SARS-CoV-2 may damage beta cells by triggering proinflammatory cytokines. Proinflammatory pathways leading to chronic low-grade inflammation in adipose tissue play an important role in the pathogenesis of insulin resistance and type 2 diabetes. Consequently, new-onset hyperglycaemia and insulin resistance have been reported in patients with coronavirus disease-2019 (Covid-19) without history of diabetes. However, it is unclear whether such metabolic alterations are transient or whether individuals with Covid-19 have an increased future risk of persisting diabetes. The aim of this study was to investigate diabetes incidence after Covid-19 in individuals with mostly mild disease treated in primary care. Individuals with acute upper respiratory tract infections (AURI), which are also frequently caused by viruses (e.g. rhinoviruses), were selected as a non-exposed control group. …”

Rathmann, W., Kuss, O. & Kostev, K. Incidence of newly diagnosed diabetes after Covid-19. Diabetologia(2022). https://doi.org/10.1007/s00125-022-05670-0


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