Exploring viral infections' role in Kawasaki disease onset: A study during the COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, known viral diseases declined in all ages. By using the current situation as a natural experiment, this study aimed to evaluate whether the change in the incidence of Kawasaki disease (KD) during the COVID-19 pandemic varies with age and whether a specific infectious disease mediates the occurrence of KD. Monthly number of KD patients were extracted from the nationwide inpatient database. Segmented regression analysis was conducted on the interrupted time series data. Additionally, causal mediation analysis was performed to examine the role of viral infections in the changes in the number of KD patients. After the first emergency declaration for COVID-19 in Japan, there was an immediate decrease in the number of KD patients per 100 000 population aged between 6 months and 4 years (immediate change = -2.66; 95% confidence interval [CI]: -5.16 to -0.16) and aged 5-15 years (immediate change = -0.26; 95% CI: -0.49 to -0.04). However, no immediate change was observed in patients under 6 months of age. In the causal mediation analysis for each viral infection, it was found that the decrease in the number of patients with KD was mediated by changes in the number of patients with pharyngoconjunctival fever and infectious gastroenteritis. The current results suggest that viral infections may be one of the etiological agents for KD, while they may not be the main cause in early infancy. Specifically, we found that adenovirus infection and gastroenteritis was closely related to the onset of KD in some areas of Japan.

Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder.

Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be triggered by viral infection of the brain is unknown. We used a target-enrichment, deep sequencing platform and bioinformatic pipeline named "ViroFind", for the unbiased characterization of DNA and RNA viruses in brain samples obtained from the National Neuro-AIDS Tissue Consortium. We analyzed fresh frozen post-mortem prefrontal cortex from 72 individuals without known viral infection of the brain, including 16 HIV+/SUD+, 20 HIV+/SUD-, 16 HIV-/SUD+, and 20 HIV-/SUD-. The average age was 52.3 y and 62.5% were males. We identified sequences from 26 viruses belonging to 11 viral taxa. These included viruses with and without known pathogenic potential or tropism to the nervous system, with sequence coverage ranging from 0.03 to 99.73% of the viral genomes. In SUD+ people, HIV-infection was associated with a higher total number of viruses, and HIV+/SUD+ compared to HIV-/SUD+ individuals had an increased frequency of Adenovirus (68.8 vs 0%; p<0.001) and Epstein-Barr virus (EBV) (43.8 vs 6.3%; p=0.037) as well as an increase in Torque Teno virus (TTV) burden. Conversely, in HIV+ people, SUD was associated with an increase in frequency of Hepatitis C virus, (25 in HIV+/SUD+ vs 0% in HIV+/SUD-; p=0.031). Finally, HIV+/SUD- compared to HIV-/SUD- individuals had an increased frequency of EBV (50 vs 0%; p<0.001) and an increase in TTV viral burden, but a decreased Adenovirus viral burden. These data demonstrate an unexpectedly high variety in the human brain virome, identifying targets for future research into the impact of these taxa on the central nervous system. ViroFind could become a valuable tool for monitoring viral dynamics in various compartments, monitoring outbreaks, and informing vaccine development.

Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation.

Introduction: Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI. Methods: We investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection (de novo or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x106 or 0.15x106 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x106 or 1.5x106 T cells/kg, respectively, at 6 months after alloSCT. Results: For both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x106/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival. Conclusion: These data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.

Squamous Cell Carcinoma of the Supraglottis Presenting as Hoarseness.

Hoarseness is a well-known condition in primary care offices, with over 1% of primary care visits secondary to this ailment.1 The most common causes are acute laryngitis (40%), functional dysphonia (30%), benign and malignant tumors (2.2 to 30%), neurogenic factors such as vocal cord paralysis (8%), physiological aging (2%), and psychogenic factors (2.2%). Most of these cases are secondary to viral infections and do not require antibiotics on most occasions. These viral infections subside after 1 to 2 weeks, and in the case of persistent hoarseness (above 4 weeks) the American Academy of Otolaryngology recommends direct visualization with a laryngoscopy before treatment with proton pump inhibitors, antibiotics, or steroids. Our patient presented with prolonged hoarseness (greater than eight weeks) but had a quick turn around time interval between primary care visit and laryngoscopy evaluation (less than 2 weeks). This led to her diagnosis and treatment with chemo and radiation therapy within three months of diagnosis with Squamous Cell Carcinoma of the Supraglottis. The Primary care physician serves as the number one point of visitation by sufferers of hoarseness. It is important that they are knowledgeable and up to date with recommendations and guidelines for managing this condition, as unwarranted delay can affect overall outcome on the part of the patient. This is especially important in patients such as ours with high risk factors including Nicotine dependence, alcohol use, asbestos exposure, and HPV infection.

La voix rauque est une condition bien connue dans les cabinets de soins primaires, avec plus de 1 % des visites en soins primaires dues à ce problème. Les causes les plus courantes sont la laryngite aiguë (40%), la dysphonie fonctionnelle (30 %), les tumeurs bénignes et malignes (2,2 à 30 %), les facteurs neurogènes tels que la paralysie des cordes vocales (8 %), le vieillissement physiologique (2 %) et les facteurs psychogènes (2,2 %). La plupart de ces cas sont dus à des infections virales et ne nécessitent pas d'antibiotiques dans la plupart des cas. Ces infections virales disparaissent après 1 à 2 semaines, et en cas de voix rauque persistante (plus de 4 semaines), l'American Academy of Otolaryngology recommande une visualisation directe avec une laryngoscopie avant le traitement par inhibiteurs de la pompe à protons, antibiotiques ou stéroïdes. Notre patiente présentait une voix rauque prolongée (plus de huit semaines), mais a bénéficié d'un délai rapide entre la visite en soins primaires et l'évaluation par laryngoscopie (moins de 2 semaines). Cela a conduit à son diagnostic et à son traitement par chimiothérapie et radiothérapie dans les trois mois suivant le diagnostic de carcinome épidermoïde du supraglotte. Le médecin de soins primaires est le premier point de visite pour les personnes souffrant de voix rauque. Il est important qu'ils soient informés et à jour des recommandations et des lignes directrices pour la prise en charge de cette condition, car un retard non justifié peut affecter le résultat global pour le patient. Ceci est particulièrement important chez les patients comme le nôtre présentant des facteurs de risque élevés, y compris la dépendance à la nicotine, la consommation d'alcool, l'exposition à l'amiante. MOTS-CLÉS: Laryngoscopie, Supraglotte, Larynx, Enrouement.

Late transplant-associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections.

OBJECTIVES: To describe late transplant-associated thrombotic microangiopathy (TA-TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: BM specimens along with conventional diagnostic parameters were assessed in 14 single-institutional patients with late TA-TMA (more than 100 days after HCST), including 11 late with history of early TA-TMA, 10 with early TA-TMA (within 100 days), and 12 non TA-TMA patients. Three non-HSCT patients served as control. The time points of BM biopsy were +1086, +798, +396, and +363 days after HSCT, respectively. RESULTS: Late TA-TMA patients showed an increase of CD34+ and von Willebrand Factor (VWF)+ microvascular endothelial cells with atypical VWF+ conglomerates forming thickened VWF+ plaque sinus in the BM compared to patients without late TA-TMA and non-HSCT. Severe chronic (p = .002), steroid-refractory GVHD (p = .007) and reactivation of HHV6 (p = .002), EBV (p = .003), and adenovirus (p = .005) were pronounced in late TA-TMA. Overall and relapse-free survival were shorter in late TA-TMA than in patients without late TA-TMA (5-year OS and RFS: 78.6% vs. 90.2%, 71.4% vs. 86.4%, respectively). CONCLUSION: Chronic allo-immune microangiopathy in BM associated with chronic, steroid-refractory GVHD and/or viral infections are key findings of late, high-risk TA-TMA, which deserves clinical attention.

Oral manifestations associated with neutropenia in Syrian patients diagnosed with hematological malignancies and undergoing chemotherapy: A cross-sectional study.

Neutropenia can be caused by a variety of congenital and acquired factors, with Chemotherapy-induced myelosuppression being the most common cause. Neutropenia significantly affects oral health, leading to the manifestation of oral lesions such as ulcers, fungal and viral infections, and mucositis. This study aims to investigate oral lesions in patients with hematological malignancies who developed neutropenia after chemotherapy. This cross-sectional study included 50 patients with hematological malignancies. The participants were divided into 2 groups: the first group consisted of 25 patients with hematological malignancies who developed chemotherapy-induced neutropenia and the second group consisted of 25 patients with hematological malignancies who did not develop chemotherapy-induced neutropenia. Patients were assigned to one of the groups based on the absolute neutrophil count (ANC). Full oral clinical examination was performed to determine the presence of oral lesions. In the Chemotherapy-Induced Neutropenia group, the most common lesion was ulceration, observed in 12 patients (48%). Fungal infections were the second most common, present in 5 patients (20%), followed by viral infections in 4 patients (15%), and mucositis, which occurred in a single patient (4%). A statistically significant association was found between neutropenia and the presence of oral ulcers (P value = .015). In contrast, in the Chemotherapy group, oral changes were less frequent. Fungal infections were the most common, occurring in 4 patients (15%), followed by oral mucositis in 3 patients (12%). Ulceration and viral infections were the least common, each observed in 1 patient (4%). The frequency of various forms of oral ulcers increases with the severity of neutropenia. However, there was no significant increase in other oral lesions in patients with neutropenia.

Role of the VEGF in virus-associated cancers.

The role of numerous risk factors, including consumption of alcohol, smoking, having diet high in fat and sugar and many other items, on caner progression cannot be denied. Viral diseases are one these factors, and they can initiate some signalling pathways causing cancer. For example, they can be effective on providing oxygen and nutrients by inducing VEGF expression. In this review article, we summarised the mechanisms of angiogenesis and VEGF expression in cancerous tissues which are infected with oncoviruses (Epstein-Barr virus, Human papillomavirus infection, Human T-lymphotropic virus, Kaposi's sarcoma-associated herpesvirus, Hepatitis B and hepatitis C virus).

Prevalence and Clinical Impact of Respiratory Viral Infections from the STOP2 Study of Cystic Fibrosis Pulmonary Exacerbations.

Rationale: Rates of viral respiratory infection (VRI) are similar in people with cystic fibrosis (CF) and the general population; however, the associations between VRI and CF pulmonary exacerbations (PEx) require further elucidation.Objectives: To determine VRI prevalence during CF PEx and evaluate associations between VRI, clinical presentation, and treatment response.Methods: The STOP2 (Standardized Treatment of Pulmonary Exacerbations II) study was a multicenter randomized trial to evaluate different durations of intravenous antibiotic therapy for PEx. In this ancillary study, participant sputum samples from up to three study visits were tested for respiratory viruses using multiplex polymerase chain reactions. Baselines and treatment-associated changes in mean lung function (percent predicted forced expiratory volume in 1 s), respiratory symptoms (Chronic Respiratory Infection Symptom Score), weight, and C-reactive protein were compared as a function of virus detection. Odds of PEx retreatment within 30 days and future PEx hazard were modeled by logistic and Cox proportional hazards regression, respectively.Results: A total of 1,254 sputum samples from 621 study participants were analyzed. One or more respiratory viruses were detected in sputum samples from 245 participants (39.5%). Virus-positive participants were more likely to be receiving CF transmembrane conductance regulator modulator therapy (45% vs. 34%) and/or chronic azithromycin therapy (54% vs. 44%) and more likely to have received treatment for nontuberculous Mycobacterium infection in the preceding 2 years (7% vs. 3%). At study visit 1, virus-positive participants were more symptomatic (mean Chronic Respiratory Infection Symptom Score, 53.8 vs. 51.1), had evidence of greater systemic inflammation (log10 C-reactive protein concentration, 1.32 log10 mg/L vs. 1.23 log10 mg/L), and had a greater drop in percent predicted forced expiratory volume in 1 second from the prior 6-month baseline (5.8 vs. 3.6). Virus positivity was associated with reduced risk of future PEx (hazard ratio, 0.82; 95% confidence interval, 0.69-0.99; P = 0.034) and longer median time to next PEx (255 d vs. 172 d; P = 0.021) compared with virus negativity.Conclusions: More than one-third of STOP2 participants treated for a PEx had a positive test result for a respiratory virus with more symptomatic initial presentation compared with virus-negative participants, but favorable long-term outcomes. More refined phenotyping of PEx, taking VRIs into account, may aid in optimizing personalized management of PEx.Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

The association between various viral infections and multiple sclerosis: An umbrella review on systematic review and meta-analysis.

Multiple Sclerosis (MS) is one of the immune-mediated demyelinating disorders. Multiple components, including the environment and genetics, are possible factors in the pathogenesis of MS. Also, it can be said that infections are a key component of the host's response to MS development. Finally, we evaluated the relationship between different pathogens and MS disease in this umbrella research. We systematically collected and analysed multiple meta-analyses focused on one particular topic. We utilised the Scopus, PubMed, and Web of Science databases starting with inception until 30 May 2023. The methodological quality of the analysed meta-analysis has been determined based on Assessing the Methodological Quality of Systematic Reviews 2 and Grade, and graph construction and statistical analysis were conducted using Comprehensive Meta-Analysis. The Confidence Interval of effect size was 95% in meta-analyses, and p < 0.05 indicated a statistically meaningful relationship. The included studies evaluated the association between MS and 12 viruses containing SARS-CoV-2, Epstein-Barr virus (EBV), Hepatitis B virus, varicella-zoster virus (VZV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, HSV-1, HSV-2, Cytomegalovirus, Human Papillomavirus, and influenza. SARS-CoV-2, with a 3.74 odds ratio, has a significantly more potent negative effect on MS among viral infections. After that, EBV, HHV-6, HSV-2, and VZV, respectively, with 3.33, 2.81, 1.76, and 1.72 odds ratios, had a significantly negative relationship with MS (p < 0.05). Although the theoretical evidence mostly indicates that EBV has the greatest effect on MS, recent epidemiological studies have challenged this conclusion and put forward possibilities that SARS-CoV-2 is the culprit. Hence, it was necessary to investigate the effects of SARS-CoV-2 and EBV on MS.

Shotgun metagenomics to investigate unknown viral etiologies of pediatric meningoencephalitis.

INTRODUCTION: Meningoencephalitis in children poses a diagnostic challenge, as etiology remains unknown for most of patients. Viral metagenomics by shotgun sequencing represents a powerful tool for investigating unknown viral infections related to these cases. PATIENTS AND METHODS: In a two-year, reference-centre, retrospective study, we investigated the usefulness of viral metagenomics of cerebrospinal fluid (CSF) for the diagnosis of viral infectious meningoencephalitis in forty seven pediatric patients, forty of them previously tested negative with a routine neurologic panel of viral targets that included herpesvirus 1-3 and enterovirus. We enhanced the detection by targeting viral sequences by hybrid capture. Raw sequence data was analysed using three bioinformatics pipelines. RESULTS: Out of forty remaining children with meningoencephalitis of unknown viral etiology, a significant detection of viral nucleic acid by shotgun sequencing was found in twenty one, which was confirmed in ten of them by specific PCR: seven human endogenous retrovirus K113 (HER K113), one parechovirus 3, one human herpesvirus 5 (HHV5); one enterovirus B (Echovirus 9). The remaining eleven CSF were not confirmed by PCR: three rotavirus, one human herpesvirus 7 (HHV7), one influenza A, one mastadenovirus C, one sindbis virus, one torque teno virus, one human immunodeficiency virus 1 (HIV-1), one human alphaherpesvirus 3 (HHV3), one human alphaherpesvirus 2 (HHV2). CONCLUSIONS: Underutilization of currently available meningitis-encephalitis diagnostic techniques such as BioFire® FilmArray® is the main cause of undiagnosed cases of meningoencephalitis. However, in this study we detected uncommon viruses that should be considered, including virus, rotavirus, sindbis virus, influenza A virus and HHV7. No other viral sequences that could be readily linked to CNS inflammation were detected. Some findings may stem from reagent or sample contamination, as seen with papillomavirus; for others, the clinical relevance of the virus remains uncertain and should be substantiated by further studies, as is the case with endogenous retrovirus K113 virus. Online bioinformatics pipeline CZID represents a valuable tool for analysing shotgun sequencing data in cases of neurological conditions with unknown etiology. Altogether, this study highlights the potential of shotgun sequencing in identifying previously unknown viral neuropathogens and sheds light on the interpretation issues related to its application in clinical microbiology.

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma.

Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.

[Lethal lymphocytic myocarditis-an underestimated diagnosis in infancy and childhood?] / Letale lymphozytäre Myokarditis ­ eine unterschätzte Diagnose im Säuglings- und Kindesalter?

In the past, histological diagnosis of (post-)viral myocarditis was based on the so-called Dallas criteria, which have been criticized because of high interobserver variability and sampling error. Immunohistochemical qualification and quantification of interstitial intramyocardial leucocytes was established and standard values concerning adults were published. Fatal casualties due to a viral myocarditis are rare as far as babies and children are concerned (sudden unexpected death in infancy; SUDI). Cases of sudden unexpected death in the first year of life are frequently regarded as sudden infant death syndrome (SIDS). To diagnose myocarditis when there are only single focal lymphocytic infiltrates in the myocardium, the number of samples taken by autopsy is relevant. But even in babies, immunohistochemical qualification and quantification of interstitial lymphocytes and macrophages can lead to standard values allowing diagnosis of myocarditis. Depending on the course of a viral infection, molecular pathological detection of viral genome in the myocardium is possible to support the diagnosis. Using the mentioned methods gradually, there are more cases of suspected SIDS, which are in fact cases of virus-induced myocarditis as cause of death. Primary enteroviruses (coxsackie viruses) and adenoviruses were found but also Epstein-Barr virus and PVB-19.

Effect of Viral Illness on Procalcitonin as a Predictor of Bacterial Infection in Febrile Infants.

OBJECTIVE: The impact of confirmed viral infections (CVI) on procalcitonin (PCT) levels in febrile infants aged 8-60 days with a bacterial illness (BI) is unknown. The objectives of the study were to (1) examine the association of CVI with PCT levels in patients with/without a concurrent BI, defined as bacteremia, meningitis, or urinary tract infection, and (2) assess PCT as a predictor of BI in infants with a concurrent CVI. METHODS: In this single-center, retrospective cohort study, we examined febrile infants aged 8-60 days presenting between January 1, 2018 and December 31, 2020. PCT levels were compared between groups, according to results of bacterial cultures and viral tests, using the Wilcoxon rank test. The prediction ability of PCT to detect BI with/without concurrent CVI was assessed by using area under the curve from logistic regression. RESULTS: Patients included: 404 BI-/CVI+, 73 BI+/CVI-, 48 BI+/CVI+, and 138 BI-/CVI-. Median PCT level in the BI+/CVI+ group was significantly lower when compared to BI+/CVI- (0.36 ng/mL vs 0.89 ng/mL), but significantly higher than the BI-/CVI- group (0.36 ng/mL vs 0.1 ng/mL). The presence of a CVI reduced the sensitivity of PCT in BI detection (68% vs 44%), with minimal impact specificity (93% vs 96%). CONCLUSIONS: In previously healthy febrile infants 8-60 days old, the presence of a CVI reduces the sensitivity of PCT BI detection without impacting its specificity. The impact of a CVI on PCT levels in febrile infants has implications for how this marker of infection should be considered when assessing risk of BI in infants.

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

BACKGROUND: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients. METHODS: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased). RESULTS: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls. CONCLUSION: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Alzheimer's disease as a viral disease: Revisiting the infectious hypothesis.

Alzheimer's disease (AD) represents the most frequent type of dementia in elderly people. Two major forms of the disease exist: sporadic - the causes of which have not yet been fully understood - and familial - inherited within families from generation to generation, with a clear autosomal dominant transmission of mutations in Presenilin 1 (PSEN1), 2 (PSEN2) or Amyloid Precursors Protein (APP) genes. The main hallmark of AD consists of extracellular deposits of amyloid-beta (Aß) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein. An ever-growing body of research supports the viral infectious hypothesis of sporadic forms of AD. In particular, it has been shown that several herpes viruses (i.e., HHV-1, HHV-2, HHV-3 or varicella zoster virus, HHV-4 or Epstein Barr virus, HHV-5 or cytomegalovirus, HHV-6A and B, HHV-7), flaviviruses (i.e., Zika virus, Dengue fever virus, Japanese encephalitis virus) as well as Human Immunodeficiency Virus (HIV), hepatitis viruses (HAV, HBV, HCV, HDV, HEV), SARS-CoV2, Ljungan virus (LV), Influenza A virus and Borna disease virus, could increase the risk of AD. Here, we summarized and discussed these results. Based on these findings, significant issues for future studies are also put forward.

Hemophagocytic lymphohistiocytosis secondary to virus infection and followed by lupus nephritis recurrence in a renal transplantation pediatric recipient: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon. CASE PRESENTATION: We described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now. CONCLUSIONS: The main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.

Viral Infections and Schizophrenia: A Comprehensive Review.

Schizophrenia is a complex mental disorder with multiple genetic and environmental factors contributing to its pathogenesis. Viral infections have been suggested to be one of the environmental factors associated with the development of this disorder. We comprehensively review all relevant published literature focusing on the relationship between schizophrenia and various viral infections, such as influenza virus, herpes virus 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), retrovirus, coronavirus, and Borna virus. These viruses may interfere with the normal maturation of the brain directly or through immune-induced mediators, such as cytokines, leading to the onset of schizophrenia. Changes in the expression of critical genes and elevated levels of inflammatory cytokines have been linked to virally-induced infections and relevant immune activities in schizophrenia. Future research is necessary to understand this relationship better and provide insight into the molecular mechanisms underlying the pathophysiology of schizophrenia.

Viral Coinfections in Kawasaki Disease: A Meta-analysis.

CONTEXT: Viral infections are suspected triggers in Kawasaki disease (KD); however, a specific viral trigger has not been identified. OBJECTIVES: In children with KD, to identify (1) overall prevalence of viral infections; (2) prevalence of specific viruses; and (3) whether viral positivity was associated with coronary artery aneurysms (CAAs) or refractoriness to intravenous immunoglobin (IVIG). DATA SOURCES: We searched Embase, Medline, and Cochrane databases and gray literature. STUDY SELECTION: Eligible studies were conducted between 1999 and 2019, and included children diagnosed with KD who underwent viral testing. DATA EXTRACTION: Two investigators independently reviewed full-text articles to confirm eligibility, extract data, appraise for bias, and assess evidence quality for outcomes using the Grading of Recommendations Assessment Development and Evaluation criteria. We defined viral positivity as number of children with a positive viral test divided by total tested. Secondary outcomes were CAA (z score ≥2.5) and IVIG refractoriness (fever ≥36 hours after IVIG). RESULTS: Of 3189 unique articles identified, 54 full-text articles were reviewed, and 18 observational studies were included. Viral positivity weighted mean prevalence was 30% (95% confidence interval [CI], 14-51) and varied from 5% to 66%, with significant between-study heterogeneity. Individual virus positivity was highest for rhinovirus (19%), adenovirus (10%), and coronavirus (7%). Odds of CAA (odds ratio, 1.08; 95% CI, 0.75-1.56) or IVIG refractoriness (odds ratio, 0.88; 95% CI, 0.58-1.35) did not differ on the basis of viral status. LIMITATIONS: Low or very low evidence quality. CONCLUSIONS: Viral infection was common with KD but without a predominant virus. Viral positivity was not associated with CAAs or IVIG refractoriness.

The role of viruses in human acute appendicitis: a systematic literature review.

BACKGROUND: There have been debates about the human appendix function, and while previous research suggested it might be a vestigial organ with no functional significance, recent studies have pointed out that it might have an important role in the immune system. Acute appendicitis (AA) is a common cause of emergency abdominal surgery in the world. Some epidemiologic investigations have found an association between appendicitis and viral infections. In this study, we have reviewed systematically articles to discover viral infections that cause appendicitis and find any possible correlations between the two. METHODS: This systematic review was performed by searching among electronic databases including Web of Science, PubMed, Scopus, and EMBASE on viruses and appendicitis topics. RESULTS: Conducted search leads to 983 results in all databases after the duplicate removal and screening by title, abstract, and full-text based on inclusion criteria lead to 19 studies. There were several assays to detect the viruses, which are thought to be AA causative agents. RT-PCR and immunoassays were the mainstay methods to detect the probable cause. CONCLUSION: Investigations suggested that some viruses including measles virus (MV), influenza virus, dengue fever virus (DFV), human immunodeficiency virus (HIV), human herpesviruses, rotavirus, and adenovirus are associated with acute appendicitis. Despite the available reports, the specific mechanisms behind the relationship between acute appendicitis and viral infections are yet to be understood. Therefore, further investigations are necessary to find out the pathogenesis and pathophysiology of viral complications in appendicitis.

Association Between Inflammatory Bowel Disease and Viral Infections.

Chronic inflammatory gastrointestinal diseases such as Crohn's disease (CD) and ulcerative colitis (UC) are known as inflammatory bowel disorders (IBD). Patients with inflammatory bowel illnesses are more susceptible to viral infections. In people with IBD, viral infections have emerged as a significant issue. Viral infections are often difficult to identify and have a high morbidity and fatality rate. We reviewed studies on viral infections and IBD, concentrating on Cytomegalovirus (CMV), SARS-CoV-2, Epstein-Barr virus (EBV), enteric viruses, and hepatitis B virus (HBV). Also, the effect of IBD on these viral infections is discussed. These data suggest that patients with IBD are more likely to get viral infections. As a result, practitioners should be aware of the increased risk of viral infections in inflammatory bowel disease patients.