Epstein-Barr Virus Seropositivity Research Articles

POTENTIAL CAUSAL ASSOCIATION BETWEEN HUMAN CYTOMEGALOVIRUS INFECTION AND CHRONIC BACK PAIN: A ONE-SAMPLE MENDELIAN RANDOMIZATION STUDY

BackgroundChronic back pain (CBP) is a major cause of disability globally and its causes are multifactorial. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are human herpes viruses usually acquired in early life. About 50% and over 90% of the population worldwide have been infected with CMV and EBV, respectively. This study investigated a potential causal relationship between CMV infection and CBP.MethodUK Biobank participants provided information on CMV seropositivity and CBP status, which were available for both traits in 5,140 participants. We used EBV seropositivity as a negative control to identify confounding and inaccurate causal inference. A one-sample Mendelian randomization (MR) based on independent genetic variants predicting CMV and EBV positivity was conducted in Northern European participants. To validate the association further, the MR study was repeated using a CMV polygenic risk score (PRS).ResultsCMV GWAS revealed 86 independent SNPs having p-value < 2 × 10−4 for the one-sample MR. These SNPs were used to define genetically-predicted categories of CMV infection risk. CMV infection risk categories were significantly associated with CBP (OR = 1.150; 95% CI: 1.005–1.317, p-value = 0.043), findings which were confirmed using the CMV PRS (OR = 1.299; 95% CI: 1.141–1.479, p-value = 0.001). There was no causal association between EBV and CBP (p-value = 0.17).ConclusionOur results provide further evidence for a causal relationship between CMV infection and CBP. These results suggest a stratified approach to CBP may be useful, particularly in clinical trials and they shed light on underlying mechanisms in CBP.Conflicts of interestNo conflicts of interestSources of fundingNo funding obtainedAcknowledgementUKBB data were obtained under the project #18219Some aspects of this work have been previously presented at The Challenge of Chronic Pain: From Genomics to Therapy in UK and first 1st Danish International Conference on Personalised Medicine in Denmark.

Modeling antigen-specific [formula omitted] cell dynamics following Hepatitis B Vaccination indicates differences between conventional and regulatory [formula omitted] cell dynamics

Our study aims to investigate the dynamics of conventional memory T cells (Tconv) and regulatory memory T cells (Treg) following activation, and to explore potential differences between these two cell types. To achieve this, we developed advanced statistical mixed models based on mathematical models of ordinary differential equations (ODE), which allowed us to transform post-vaccination immunological processes into mathematical formulas. These models were applied to in-house data from a de novo Hepatitis B vaccination trial. By accounting for inter- and intra-individual variability, our models provided good fits for both antigen-specific Tconv and Treg cells, overcoming the challenge of studying these complex processes. Our modeling approach provided a deeper understanding of the immunological processes underlying T cell development after vaccination. Specifically, our analysis revealed several important findings regarding the dynamics of Tconv and Treg cells, as well as their relationship to seropositivity for Herpes Simplex Virus Type 1 (HSV-1) and Epstein-Barr Virus (EBV), and the dynamics of antibody response to vaccination. Firstly, our modeling indicated that Tconv dynamics suggest the existence of two T cell types, in contrast to Treg dynamics where only one T cell type is predicted. Secondly, we found that individuals who converted to a positive antibody response to the vaccine earlier had lower decay rates for both Tregs and Tconv cells, which may have important implications for the development of more effective vaccination strategies. Additionally, our modeling showed that HSV-1 seropositivity negatively influenced Tconv cell expansion after the second vaccination, while EBV seropositivity was associated with higher Treg expansion rates after vaccination. Overall, this study provides a critical foundation for understanding the dynamic processes underlying T cell development after vaccination.

Viral DNAemia and DNA Virus Seropositivity and Mortality in Pediatric Sepsis

Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis. To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study. This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG antibodies to CMV, EBV, HSV-1, or HHV-6. A total of 401 patients younger than 18 years with severe sepsis were enrolled from 9 pediatric intensive care units (PICUs) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Data were collected from 2015 to 2018. Samples were assayed from 2019 to 2022. Data were analyzed from 2022 to 2023. Death while in the PICU. Among the 401 patients included in the analysis, the median age was 6 (IQR, 1-12) years, and 222 (55.4%) were male. One hundred fifty-four patients (38.4%) were previously healthy, 108 (26.9%) were immunocompromised, and 225 (56.1%) had documented infection(s) at enrollment. Forty-four patients (11.0%) died in the PICU. Viral DNAemia with at least 1 virus (excluding TTV) was detected in 191 patients (47.6%) overall, 63 of 108 patients (58.3%) who were immunocompromised, and 128 of 293 (43.7%) who were not immunocompromised at sepsis onset. After adjustment for age, Pediatric Risk of Mortality score, previously healthy status, and immunocompromised status at sepsis onset, CMV (adjusted odds ratio [AOR], 3.01 [95% CI, 1.36-6.45]; P = .007), HAdV (AOR, 3.50 [95% CI, 1.46-8.09]; P = .006), BKPyV (AOR. 3.02 [95% CI, 1.17-7.34]; P = .02), and HHV-6 (AOR, 2.62 [95% CI, 1.31-5.20]; P = .007) DNAemia were each associated with increased mortality. Two or more viruses were detected in 78 patients (19.5%), with mortality among 12 of 32 (37.5%) who were immunocompromised and 9 of 46 (19.6%) who were not immunocompromised at sepsis onset. Herpesvirus seropositivity was common (HSV-1, 82 of 246 [33.3%]; CMV, 107 of 254 [42.1%]; EBV, 152 of 251 [60.6%]; HHV-6, 253 if 257 [98.4%]). After additional adjustment for receipt of blood products in the PICU, EBV seropositivity was associated with increased mortality (AOR, 6.10 [95% CI, 1.00-118.61]; P = .049). The findings of this cohort study suggest that DNAemia for CMV, HAdV, BKPyV, and HHV-6 and EBV seropositivity were independently associated with increased sepsis mortality. Further investigation of the underlying biology of these viral DNA infections in children with sepsis is warranted to determine whether they only reflect mortality risk or contribute to mortality.

Epstein-Barr virus seroprevalence among inflammatory bowel disease patients in Saudi Arabia.

Seroprevalence of Epstein-Barr virus (EBV) in patients with inflammatory bowel disease (IBD) is variable based on geographic distribution. There are no published data on the seroprevalence of EBV in patients with IBD in Saudi Arabia. This study aims to assess the seroprevalence of EBV in patients with IBD in a tertiary center in Saudi Arabia. This is a retrospective chart review of patients ≥14 years of age with a confirmed diagnosis of IBD and known EBV status at our institution from January 1, 2018, to January 1, 2023. The primary outcome was the seroprevalence of EBV in IBD. Secondary outcomes included factors associated with EBV seropositivity and rates of EBV seroconversion in originally negative patients. A total of 150 patients were included (74.7% with Crohn's disease, median age 28 years [interquartile range 21-36.3]). EBV non-exposure was noted in 16.8% ( n = 25). The mean age was significantly lower in the EBV-naïve group at 26 ± 8.5 years compared to the EBV-exposed group at 31.2 ± 12.9 years ( P = 0.02). Seroprevalence of EBV was highest in patients >40 years of age (92.9%) and lowest in patients 14-25 years of age (78.2%). The rate of seroconversion in EBV-naïve patients was 16.7% after a mean follow-up time of 47.9 ± 46.3 months. In our cohort of IBD patients, 16.8% were naïve to EBV, and young age was a significant predictor of EBV non-exposure. Our data supports the practice of assessing EBV before initiating thiopurine therapy since EBV seroprevalence is not universal in our population.

Epstein Barr Virus nuclear antigen and sociodemographical characteristics of HIV-infected individuals in two tertiary health facilities in Rivers State, Nigeria

Epstein-Barr virus (EBV) is one of the opportunistic pathogens that affects HIV infected individuals. Although high prevalence of EBV has been well documented in Africa and some parts of Nigeria, such data are sparse from Rivers State, Nigeria. Thus, this study aimed at determining the Epstein Barr virus nuclear antigens and the sociodemographical characteristics of HIV-infected individuals in two tertiary hospitals in Rivers State, Nigeria. Plasma from 182 HIV-infected individuals attending the Retroviral Clinics of UPTH and RSUTH in Rivers State, Nigeria were tested for antibodies specific for EBNA by IgM ELISA assays. Overall prevalence of IgM antibodies against Epstein Barr Nucleic Acid (EBNA) was 20.9%. The study showed sex-related statistical variances in the seropositivity of anti-IgM (females 23.5% vs. males 16.4%, p<0.05). Higher seropositivity occurred in age range 0-20 years (25.0%) than other age range, divorced and widowed (50.0%) than the married (25.7%) and singles (10.1%), among tertiary education (24.7%) than secondary (20.5%) and primary education (8.3%), Islamic religion (56.3%) than Christian religion (17.5%), and social/healthcare workers (37.5%) than other occupational groups. Summarily, higher seropositivity of anti-IgM antibodies against EBV was observed in HIV-infected individuals in UPTH than their counterparts in RSUTH. Nevertheless, 20.9% of the HIV-infected individuals in this study that were categorized with current/ongoing primary infection, owed to VCA-IgM detection, were positive for EBNA IgM antibodies. In conclusion, this study clearly confirmed that EBV seropositivity considerably increased with age, sex, marital status, educational level, religion, and occupation. Thus, this study verified earlier studies that presented high EBV seroprevalence, touching >50.0%the populace in Nigeria. Future larger and multi-center clinical research are suggested to address some unanswered seroepidemiological questions.

Epstein–Barr virus (EBV) antibody changes over time in a general population cohort in rural Uganda, 1992–2008

BackgroundEpstein–Barr virus (EBV) infection is ubiquitous and in sub-Saharan Africa, occurs early in life. In a population-based rural African cohort, we leveraged historical samples from the General Population Cohort (GPC) in Uganda to examine the epidemiology of infection with EBV over time, in the era of HIV.MethodsWe used 9024 serum samples collected from the GPC in 1992, 2000, 2008, from 7576 participants across the age range (0–99 years of age) and tested for anti-EBV immunoglobulin G (IgG) antibodies to EAd, VCA, and EBNA-1 using a multiplex bead-based assay. The related gammaherpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV) seropositivity was also determined by detection of anti-KSHV IgG antibodies to K8.1 or ORF73 measured by recombinant protein enzyme-linked immunosorbent assay. Data on sex, age, and HIV serostatus were also collected. EBV seropositivity was modeled with age (excluding those under one year, who may have had maternal antibodies), sex, HIV serostatus, and KSHV serostatus using generalized linear mixed effects models to produce beta estimates.ResultsMore than 93% of children were EBV seropositive by one year of age. EBV seropositivity was significantly associated with KSHV seropositivity. Anti-EBNA-1 antibody levels decreased with increasing age and were lower on average in people living with HIV. In general, anti-EAd antibody levels increased with age, were higher in males and KSHV seropositive persons, but decreased over calendar time. Anti-VCA antibody levels increased with age and with calendar time and were higher in KSHV seropositive persons but lower in males.ConclusionsThis is the first study to identify factors associated with EBV antibodies across the entire life-course in rural sub-Saharan Africa. Consistent with other studies, EBV was near ubiquitous in the population by age one year. Patterns of antibodies show changes by age, sex and calendar time, but no association with HIV was evident, suggesting no relationship between EBV sero-epidemiology and the spread of HIV in the population over time in Uganda.

Sero-detection of Epstein-Barr virus and Cytomegalovirus Antibodies among patients with Systemic lupus Erythematous in Sudan

Infection by Cytomegalovirus (CMV) and Epstein - Barr virus (EBV) has been implicated in the pathogenesis of Systemic lupus Erythematous (SLE). The current study aimed to determine the frequency of EBV and CMV IgG among Sudanese patients with SLE. A case-control analytical study was conducted on 82 participants in Khartoum State during the period from 2017 to 2018. Serum from patients with SLE (n=62), and controls participants (n=20) were tested for IgG antibodies against EBV and CMV using the Avidity ELISA assay. Pretested questionnaire data were analyzed by SPSS software V.20 (IBM, Chicago,IL). Means and proportions of the demographic were calculated for SLE seropositive groups. Chi-square test and binary logistic regression analysis were used for SLE as a dependent factor while IgG seropositive groups of EBV and CMV as the independent variable and, SLE variables as dependent variables. Odds ratio (OR) with a 95% confidence interval was calculated and statistical significance was defined as a P value below 0.05. Eighty-two females with SLE volunteered to participate in this study, including 62 cases with systemic lupus erythematosus and 20 control participants. Average age means ± SD (34±1.4) for cases and (34±1.6) for controls. Original tribes in Sudan were screened Avidity assay for Western State 37(45.1%), Northern State 29(35.4%), Central State 17(20.7%), and Southern State1 (1.2%) respectively. Seropositivity of IgG by Avidity assay revealed high score for CMV 60 (96.8%) among cases vs 19(95%) among controls, (OR 1.579, CI -95% (0.136-18.4), P <0.05). Seropositivity for both EBV and Co-infection was 58 (98.3%) vs 16 (80.0%) among cases and controls, respectively (OR 3.625, CI -95% (0.227-2.708), P <0.05). Patients with SLE in Sudan have a high rate of infections by EBV and CMV as evidenced by the IgG avidity test indicating association.

Multiple sclerosis in 2022: old players, new insights

2022 started with publication of two research papers that reinforced the necessary role of Epstein-Barr virus infection in the onset of multiple sclerosis. Bjornevik and colleagues1 analysed serum samples in the US Department of Defense serum repository from 801 people with multiple sclerosis and 1566 matched controls, with samples drawn before, during, and after the onset of multiple sclerosis clinical symptoms in the affected individuals. Epstein-Barr virus seropositivity, but not cytomegalovirus seropositivity, preceded multiple sclerosis onset in all patients.

Multiple sclerosis risk variants influence the peripheral B-cell compartment early in life in the general population.

Multiple sclerosis (MS) is associated with abnormal B-cell function, and MS genetic risk alleles affect multiple genes that are expressed in B cells. However, how these genetic variants impact the B-cell compartment in early childhood is unclear. In the current study, we aim to assess whether polygenic risk scores (PRSs) for MS are associated with changes in the blood B-cell compartment in children from the general population. Six-year-old children from the population-based Generation R Study were included. Genotype data were used to calculate MS-PRSs and B-cell subset-enriched MS-PRSs, established by designating risk loci based on expression and function. Analyses of variance were performed to examine the effect of MS-PRSs on total B-cell numbers (n=1261) as well as naive and memory subsets (n=675). After correction for multiple testing, no significant associations were observed between MS-PRSs and total B-cell numbers and frequencies of subsets therein. A naive B-cell-MS-PRS (n=26 variants) was significantly associated with lower relative, but not absolute, naive B-cell numbers (p=1.03 × 10-4 and p=0.82, respectively), and higher frequencies and absolute numbers of CD27+ memory B cells (p=8.83 × 10-4 and p=4.89 × 10-3 , respectively). These associations remained significant after adjustment for Epstein-Barr virus seropositivity and the HLA-DRB1*15:01 genotype. The composition of the blood B-cell compartment is associated with specific naive B-cell-associated MS risk variants during childhood, possibly contributing to MS pathophysiology later in life. Cell subset-specific PRSs may offer a more sensitive tool to define the impact of genetic risk on the immune system in diseases such as MS.

Serologic Profiling Using an Epstein-Barr Virus Mammalian Expression Library Identifies EBNA1 IgA as a Prediagnostic Marker for Nasopharyngeal Carcinoma.

The favorable prognosis of stage I and II nasopharyngeal carcinoma (NPC) has motivated a search for biomarkers for the early detection and risk assessment of Epstein-Barr virus (EBV)-associated NPC. Although EBV seropositivity is ubiquitous among adults, a spike in antibodies against select EBV proteins is a harbinger of NPC. A serologic survey would likely reveal which EBV antibodies could discriminate those at risk of developing NPC. Lysates from a new EBV mammalian expression library were used in a denaturing multiplex immunoblot assay to survey antibodies against EBV in sera collected from healthy individuals who later developed NPC (incident cases) in a prospective cohort from Singapore and validated in an independent cohort from Shanghai, P.R. China. We show that IgA against EBV nuclear antigen 1 (EBNA1) discriminated incident NPC cases from matched controls with 100% sensitivity and 100% specificity up to 4 years before diagnosis in both Singapore and Shanghai cohorts. Incident NPC cases had a greater IgG repertoire against lytic-classified EBV proteins, and the assortment of IgA against EBV proteins detected by the immunoblot assay increased closer to diagnosis. Although NPC tumors consistently harbor latent EBV, the observed heightened systemic and mucosal immunity against lytic-classified antigens years prior to clinical diagnosis is consistent with enhanced lytic transcription. We conclude that an expanding EBV mucosal reservoir (which can be latent and/or lytic) is a risk factor for NPC. This presents an opportunity to identify those at risk of developing NPC using IgA against EBNA1 as a biomarker.

Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response

Very long-chain fatty acids (VLCFA) are critical for human cytomegalovirus replication and accumulate upon infection. Here, we used Epstein-Barr virus (EBV) infection of human B cells to elucidate how herpesviruses target VLCFA metabolism. Gene expression profiling revealed that, despite a general induction of peroxisome-related genes, EBV early infection decreased expression of the peroxisomal VLCFA transporters ABCD1 and ABCD2, thus impairing VLCFA degradation. The mechanism underlying ABCD1 and ABCD2 repression involved RNA interference by the EBV-induced microRNAs miR-9-5p and miR-155, respectively, causing significantly increased VLCFA levels. Treatment with 25-hydroxycholesterol, an antiviral innate immune modulator produced by macrophages, restored ABCD1 expression and reduced VLCFA accumulation in EBV-infected B-lymphocytes, and, upon lytic reactivation, reduced virus production in control but not ABCD1-deficient cells. Finally, also other herpesviruses and coronaviruses target ABCD1 expression. Because viral infection might trigger neuroinflammation in X-linked adrenoleukodystrophy (X-ALD, inherited ABCD1 deficiency), we explored a possible link between EBV infection and cerebral X-ALD. However, neither immunohistochemistry of post-mortem brains nor analysis of EBV seropositivity in 35 X-ALD children supported involvement of EBV in the onset of neuroinflammation. Collectively, our findings indicate a previously unrecognized, pivotal role of ABCD1 in viral infection and host defence, prompting consideration of other viral triggers in cerebral X-ALD.

Epstein-Barr virus seroprevalence and viral load at disease onset in children with inflammatory bowel disease.

Background and AimPatients with inflammatory bowel disease (IBD) are at increased risk for life‐threatening complications of Epstein–Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection.MethodsWe included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2‐year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre‐treatment viral load of EBV.ResultsOne hundred twenty patients were included in the study. Fifty‐three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine.ConclusionEBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy.

Epstein-Barr virus and Burkitt’s lymphoma. Associations in Iraqi Kurdistan and twenty-two countries assessed in the International Incidence of Childhood Cancer

BackgroundBurkitt's lymphoma (BL) has worldwide variations in incidence that are related to the age of Epstein-Barr virus (EBV) infection. This study examined the age-specific incidence rate (ASIR) of BL and community EBV seropositivity in Iraqi Kurdistan and compared results with data from countries tabulated in the International Incidence of Childhood Cancer volume 3 (IICC-3).MethodsThe ASIR (95% confidence intervals) of BL in Sulaimani Governorate of Iraqi Kurdistan were calculated for the years 2010–2020. Specimens from 515 outpatients were tested for IgG and IgM antibodies to EBV viral capsid antigen.ResultsIn Sulaimani, 84% of BL occurred under 20 years of age, with an ASIR of 6.2 (4.7–7.7) per million children. This ASIR was not significantly different than that of Egypt, Morocco, Israel, Spain, or France. It was slightly higher than the ASIR of the United States, the United Kingdom, and Germany and markedly higher than for Asia and South Africa. In Africa and much of Asia, early childhood EBV exposure predominates, with nearly all children being infected by 5 years of age. In Sulaimani, just over 50% of children were EBV seropositive at 3 years old and 90% seropositivity was reached at 15 years of age. In Europe and North America, seropositivity is commonly delayed until adolescence or young adulthood and adult predominates over childhood BL.ConclusionIn the Middle East, childhood BL is relatively common and adult BL is rare. In Sulaimani, EBV seropositivity increases progressively throughout childhood and reaches 92% at mid-adolescence. This may reflect the Mid East more widely. We suggest that the high childhood and low adult BL rates may be a regional effect of a pattern of EBV exposure intermediate between early childhood and adolescent and young adult infections.

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model.

Epstein-Barr virus (EBV) establishes a lifelong latent infection in healthy humans, kept under immune control by cytotoxic T cells (CTLs). Following paediatric haematopoetic stem cell transplantation (HSCT), a loss of immune surveillance leads to opportunistic outgrowth of EBV-infected cells, resulting in EBV reactivation, which can ultimately progress to post-transplant lymphoproliferative disorder (PTLD). The aims of this study were to identify risk factors for EBV reactivation in children in the first 100 days post-HSCT and to assess the suitability of a previously reported mathematical model to mechanistically model EBV reactivation kinetics in this cohort. Retrospective electronic data were collected from 56 children who underwent HSCT at Great Ormond Street Hospital (GOSH) between 2005 and 2016. Using EBV viral load (VL) measurements from weekly quantitative PCR (qPCR) monitoring post-HSCT, a multivariable Cox proportional hazards (Cox-PH) model was developed to assess time to first EBV reactivation event in the first 100 days post-HSCT. Sensitivity analysis of a previously reported mathematical model was performed to identify key parameters affecting EBV VL. Cox-PH modelling revealed EBV seropositivity of the HSCT recipient and administration of anti-thymocyte globulin (ATG) pre-HSCT to be significantly associated with an increased risk of EBV reactivation in the first 100 days post-HSCT (adjusted hazard ratio (AHR) = 2.32, P = 0.02; AHR = 2.55, P = 0.04). Five parameters were found to affect EBV VL in sensitivity analysis of the previously reported mathematical model. In conclusion, we have assessed the effect of multiple covariates on EBV reactivation in the first 100 days post-HSCT in children and have identified key parameters in a previously reported mechanistic mathematical model that affect EBV VL. Future work will aim to fit this model to patient EBV VLs, develop the model to account for interindividual variability and model the effect of clinically relevant covariates such as rituximab therapy and ATG on EBV VL.

Serum IgG levels to Epstein-Barr and measles viruses in patients with multiple sclerosis during natalizumab and interferon beta treatment

BackgroundPatients with multiple sclerosis (MS) demonstrate higher seroprevalence of Epstein-Barr virus (EBV) and increased anti-EBV IgG levels in serum compared with healthy controls. Intrathecal antibody production to measles virus (MeV)...

Anti-EBNA1 IgG titre is not associated with fatigue in multiple sclerosis patients.

Fatigue is the most frequent symptom in multiple sclerosis (MS), although it is still poorly understood due to its complexity and subjective nature. There is an urgent need to identify reliable biomarkers to improve disease prognosis and therapeutic strategies. Epstein-Barr virus (EBV) is the major environmental risk factor associated with MS aetiology, and trials with EBV-targeted T cell therapies have reduced fatigue severity in MS patients. We investigated whether the serum amount of immunoglobulin (Ig)G-specific for EBV antigens could be a suitable prognostic marker for the assessment of MS-related fatigue. A total of 194 MS patients were enrolled. We quantified EBV nuclear antigen 1 (EBNA1) and EBV viral capsid antigen (VCA) immunoglobulin (Ig) G levels and B cell-activating factor of the tumour necrosis factor family (BAFF) concentration in the serum of patients with relapsing-remitting MS (RRMS) and chronic progressive MS (CPMS), and we analysed their correlation with aspects of fatigue and other clinical disease parameters. A complete EBV seropositivity could be detected in our cohort. After adjusting for confounding variables and covariates, neither EBNA1 nor VCA antibody titres were associated with levels of fatigue, sleepiness, depression, or with any of the clinical values such as expanded disability status scale, lesion count, annual relapse rate, or disease duration. However, patients with RRMS had significantly higher EBNA1 IgG titre than those with CPMS, whereas this was not the case under therapies targeting CD20+ cells. BAFF levels in serum were inversely proportional to anti-EBNA1 IgG. Our results show that EBNA1 IgG titre is not associated with the presence or level of fatigue. Whether the increased EBNA1 titre in RRMS plays a direct role in disease progression, or is only a consequence of excessive B cell activation, remains to be answered in future studies.

Association between solid fuel use and seropositivity against Epstein-Barr virus in a high-risk area for nasopharyngeal carcinoma

Epstein-Barr virus (EBV) is one of the risk factors of nasopharyngeal carcinoma (NPC), and understanding the modifiable risk factors of EBV activation is crucial in the prevention of NPC. In this study, we aimed to investigate the association between solid fuel use and EBV seropositivity in a high-risk area of NPC. Our study was based on the baseline findings from an ongoing population-based prospective cohort in Sihui county in Southern China. We explored the association between current use of solid fuel in cooking and EBV seropositivity, and NPC-related EBV activation, using logistic regression models. Stratification analyses were further conducted to assess potential effect modifiers. We also examined the impact of frequency and duration of solid fuel use, and switch in fuel types, on EBV seropositivity among ever users. Of the 12,579 participants included in our analysis, 4088 (32.5%) were EBV seropositive and 421 (3.3%) were high risk for NPC-related EBV activation. Solid fuel use was associated with a higher risk of EBV seropositivity and NPC-related EBV activation, with odds ratios (ORs) of 1.33 (95%CI: 1.01, 1.76) and 1.81 (95%CI: 1.03, 3.18), respectively. Higher risk of EBV seropositivity was observed for those who did not use ventilation apparatus and those who consumed salted food. Among ever users, OR was highest for participants with more than 40 years of solid fuel exposure (1.17, 95%CI: 1.00–1.37) and who have been constantly using solid fuel (1.30, 95%CI: 0.96–1.75). We did not find a statistically significant impact of cooking frequency on EBV seropositivity. The identification of solid fuel as a risk factor for EBV activation is of great value for understanding the etiology of NPC. Our findings also have important public health implications given the fact that a third of the global population still lack access to clean cooking, especially in low resource settings.

Associations of Epstein-Barr Virus Infection with Attention Deficit Hyperactivity Disorder, Learning Disability, and Special Education in US Children.

BackgroundMost infections of Epstein-Barr virus (EBV), which is potentially neurotropic, occur in childhood, but little is known about its association with child neurodevelopmental outcomes.Patients and MethodsWe investigated whether EBV seropositivity was associated with parent-reported attention deficit hyperactivity disorder (ADHD), learning disability, or special education utilization among children, using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. Potential confounding factors were adjusted using survey logistic regression models.ResultsEBV seroprevalence was 69.6% (95% CI, 67.1–72.1%) for US children aged 6–19. The prevalence was 8.86% (95% CI, 7.47–10.47%) for ADHD among 6–19 year olds, 11.70% (95% CI, 9.84–13.87%) for learning disability among 6–15 year olds, and 10.18% (95% CI, 8.58–12.05%) for special education among 6–17 year olds. Children with positive anti-EBV had higher crude prevalence rates of learning disability and special education but not ADHD compared with those with negative anti-EBV. The adjusted odds ratios were 2.76 (95% CI, 1.53–4.96) for learning disability, 3.58 (95% CI, 1.92–6.55) for special education, and 0.77 (95% CI, 0.42–1.38) for ADHD, when comparing children with positive and negative anti-EBV.ConclusionEBV seropositivity was associated with learning disability and special education among US children. Future studies that longitudinally examine the associations are warranted.

Potential impact of viral skin diseases and other viral infections on the incidence and severity of COVID-19 in renal transplant patients

Background: COVID-19 in solid organ transplant recipients is usually characterized by more severe disease course and is often associated with life-threatening complications. Identification of additional factors that may affect the risk and severity of the new coronavirus infection could have a significant impact on choosing a management strategy for renal graft recipients.&#x0D; Aim: To evaluate the possibility of cross-immunity between skin manifestations of viral etiology and COVID-19.&#x0D; Materials and methods: From May 2020 to February 2021 we examined 180 renal graft recipients with a history of transplantation from 2 months to 26.5 years. All patients were categorized into two groups: group I (n=68), those who had confirmed moderate or severe COVID-19 disease and group II (n=112), those without any history of clinical manifestations of the new coronavirus infection (including those with potentially asymptomatic disease). During the study period which lasted for 71 months on average (range, 2 to 318 months), laboratory workup was performed in all patients (on average, twice): dermatological examination and detection of serum antibodies to herpes simplex virus 1, 2, cytomegalovirus, human papilloma virus (HPV), Epstein-Barr virus, SARS-CoV-2.&#x0D; Results: In recipients with HPV-associated skin manifestations, the incidence of COVID-19 was significantly lower than in recipients who did not have them 30.4% (34/112) and 50% (34/68), respectively (p=0.011). The incidence of new coronavirus infection did not differ in the groups of patients with cutaneous manifestations caused by herpes simplex viruses type 1 and 2, and without them. Among recipients with Epstein-Barr virus seropositivity, there were significantly fewer cases of COVID-19 compared to seronegative patients 26.2% (28/107) and 54.8% (40/73), respectively (p=0.0002).&#x0D; Conclusion: HPV-associated dermal manifestations or serum Epstein-Barr virus-seropositivity in renal graft recipients is associated with lower incidence of moderate and severe COVID-19. Further studies are needed to confirm the possibility of cross-immunity against SARS-CoV-2 with other infections.

Association Between Traditional Herbal Diet and Nasopharyngeal Carcinoma Risk: A Prospective Cohort Study in Southern China.

IntroductionProspective evidence for herbal diet and nasopharyngeal carcinoma (NPC) development is absent. We therefore evaluated the associations of herbal soup and herbal tea with NPC in a prospective cohort study in southern China.MethodsBased on an NPC screening cohort established in 2008–2015, information on herbal diet consumption, potential confounding factors, and Epstein-Barr virus (EBV) antibody levels were collected from 10,179 individuals aged 30–69 years in Sihui city, southern China. Cox regression models were performed to examine herbal diet with NPC risk, and logistic regression models were used to examine herbal diet with EBV reactivation.ResultsDuring a median of 7.54 years of follow-up, 69 participants developed NPC. Herbal soup consumption was associated with decreased NPC risk, with HRs of 0.31 (95% confidence interval (CI): 0.15–0.62) for the highest intake frequency and 0.29 (95% CI: 0.16–0.51) for a longer duration. However, herbal tea was not significantly associated. Moreover, we identified herbal soup was inversely associated with EBV seropositivity among all the participants at baseline, with the adjusted ORs being 0.78 (95% CI: 0.65–0.93) for immunoglobulin A antibodies against EBV capsid antigens (VCA-IgA) and 0.76 (95% CI: 0.64–0.91) for nuclear antigen 1 (EBNA1-IgA) in those with the highest frequency and 0.70 (95% CI: 0.59–0.84) for VCA-IgA and 0.64 (95% CI: 0.54–0.77) for EBNA1-IgA in those with the longer duration. Inverse associations were also observed in non-NPC individuals.ConclusionsWith inhibition of EBV reactivation by plants, herbal soup could significantly decrease the risk of NPC in endemic areas.