Epstein-Barr Virus IgG Research Articles

Chronic active Epstein–Barr Virus infection in a teenage girl with suspect autoimmune Hepatitis

BackgroundThe pathogenesis of chronic active Epstein–Barr virus (EBV) disease (CAEBV) is complex, involving infection, inflammation, and in some cases malignancy. EBV reactivates in some patients, who develop a chronic disease with infectious mononucleosis-like symptoms. On occasion, it might be confused with autoimmune hepatitis (AIH), based on the similar symptoms and elevated liver enzymes. We aimed to describe a similar case to remind reader of this disease.Case Presentation: A 14-year-old girl was diagnosed with AIH based on biopsy and biomarker findings 1 year prior to admission and initially presented with elevated liver enzymes, portal hypertension, and parenchymal liver disease. Despite steroid administration, her condition fluctuated, and she was admitted to the hospital several times. She underwent a renal biopsy because of massive ascites, hypoalbuminemia, and increased renal echogenicity. An evaluation for impaired liver function showed positivity for EBV IgM, IgG, and early antigen (EBEA) antibodies. A PCR-based assay showed 5265 copies/mL of EBV DNA in peripheral blood. Epstein–Barr encoding region (EBER) in situ hybridization revealed abundant positive cells. Immunohistochemistry for CD56 also showed abundant positive cells, and CAEBV was diagnosed on this basis. Chemotherapy, hematopoietic stem cell transplantation (HSCT), and liver transplantation were proposed but her family refused.ConclusionsCAEBV should be considered when diagnosing AIH or in cases of treatment-refractory AIH.

Expression of Anti- Apoptotic Gene ( BARF1) and Immunomodulatory Gene (BCRF1) For Epstein Barr Virus in Chronic Active EBV Patients

Epstein Barr virus (EBV) is a herpes virus with double-stranded DNA enclosed by proteins. The envelope of the virus has glycoproteins, which are important for attachment and entry into the host cells (B cells and epithelial cells). EBV targets B cells by utilizing their molecular machinery to replicate the viral genome. The virus causes B cells to differentiate into memory B cells, which then can move into the circulatory system, or become latent until a trigger causes reactivation. The transmission of the Epstein Barr virus occurs in several ways, such as deep kissing or food-sharing. Increased levels of viral DNA are found in salivary secretions after the initial infection. Children can be infected after eating food that has already been chewed by an EBV infected individual. The transmission has occurred through stem cell and organ transplantation, as well as blood transfusion. EBV has several associated complications, One dangerous complication is splenic rupture due to infectious mononucleosis. Aim of the Study: To Estimation the immunemodulatory and Oncogenes for Epstein Barr Virus Associated with Viral Tumorigenesis in Chronic Active EBV Patients By Detection of EBV IgG in all samples , Estimation the expression of antiapoptotic gene ( BARF1) and immunomodulatory gene (BCRF1). Result: The study showed there are high significant between the patient group with different inflammation disease in addition infected with virus compare with have not disease When detection genetically about the virus in sample of infected by EBV the presence of genes has been diagnosed BARF1 and BCRF1 in patient's group.

CORRELATION OF EPSTEIN-BARR VIRUS WITH BREAST CANCER: A CASE CONTROL STUDY

Background and aims: Epstein-Barr virus (EBV) is a gamma herpes virus and one of the most common infections globally. It has been linked to several health problems, including breast cancer, which is a leading cause of death among females worldwide. In Yemen, breast cancer is one of the top reported cancers in women. This study aimed to investigate the correlation between EBV and breast cancer among Yemeni women in Sana'a city. Methods: The study is a case-control study that included newly diagnosed, untreated breast cancer patients as cases and healthy women attending the National Cancer Control Foundation as controls. A total of 150 participants were tested for EBV (VCA) IgG using ELISA. Results: The association between EBV and BC in the case and control groups was found by the investigation. 48 women (64.0%) who tested positive for EBV IgG were included in the control group, whereas 71 women (94.7%) among the patients had the antibody identified. A substantial correlation between EBV and BC was found by statistical analysis; a chi-square value of 21.510 and a p-value of less than 0.001 supported this conclusion. With a 95% confidence interval, the odds ratio was 10.0 (3.3-30.4). Moreover, women above the age of thirty showed a higher risk than women under that age (p=0.006). In addition, compared to the control group, divorced and bereaved women had a significantly higher chance of contracting EBV (p= 0.002). Conclusions: According to the study's findings, there may be a link between EBV infection and a higher risk of breast cancer. To further understand the underlying mechanisms and potential strategies to reduce this risk, more research is required. Peer Review History: Received 1 December 2023; Revised 19 January 2024; Accepted 27 February; Available online 15 March 2024 Academic Editor: Dr. Muhammad Zahid Iqbal, AIMST University, Malaysia, drmmziqbal@gmail.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Andrzej Szymański, Poznan University of Technology, Poland, andrzej.szymanski@put.poznan.pl Dr. Fátima Morales Marín, University of Murcia, Spain, fatima.morales@um.es

Can the Epstein-Barr Virus Play a Role in the Development of Prostate Cancer?

Prostate cancer (PCa) is the fourth most frequently diagnosed cancer worldwide, accounting for 7.3% of all cancers. PCa mortality is the fifth most common cause of cancer death. Despite well-known factors influencing the development of PCa, such as age, race/ethnicity and family history, many researchers have raised the possibility of persistent infections with oncogenic viruses. Therefore, we aimed to assess the frequency of Epstein-Barr virus (EBV) DNA in tissue collected from PCa patients. Next, the frequency and the level of Epstein-Barr virus capsid antigen (EBVCA) and Epstein-Barr nuclear antigen 1 (EBNA1) antibodies in both IgA and IgG classes were measured. The antibody titer was also analyzed depending on the risk group, Gleason score (GS) and tumor, node, metastasis (TNM) classification. Serum samples were analyzed using the Microblot-Array EBV IgM, IgA and IgG test kits. The study group consisted of 115 patients diagnosed and histopathologically confirmed with PCa. In 49% of patients included in the study, EBV DNA was detected in the tumor tissue. The studies showed both higher seroprevalence and higher antibody titers in patients with EBV-positive PCa compared to patients with EBV-negative PCa. We also observed a dependence of antibody titer on pathological features, such as GS, risk group and T stage.

Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course

PurposePost-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS.MethodsThe PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed.ResultsOur data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups.ConclusionOur data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.

Sequential activation of DNA viruses by the RNA virus SARS-CoV-2 in patients with long COVID syndrome

Abstract Background Reactivation of Epstein-Barr virus (EBV) has been suggested to play role in long lasting multiorgan symptoms several months after the initial COVID-19 illness. Purpose The aim of our prospective study was to 1) to evaluate the reactivation of DNA viruses of EBV, Cytomegalovirus, Herpes simplex, Varicella zoster and Parvovirus-B19 by SARS-CoV-2 in patients with the diagnosis of long-COVID syndrome, 2) to investigate the effect of supposed virus reactivation on clinical conditions and long COVID syndromes. Methods Patients with long COVID syndrome were prospectively included into the Vienna PostCoV Registry between March 15th 2021 and September 30th 2021. - The time between COVID-19 infection and first clinical visit was 219±98 days (7±3 months). Clinical symptoms were documented and patients were divided into symptoms-oriented subgroups with dominantly respiratory, cardiovascular or neuropsychologic complaints. Qualitative and quantitative viral IgG and IgM titer of the selected DNA viruses of n=105 patients were compared with age and sex-matched healthy (non-infected, non-vaccinated, n=105) controls, who had neither spike- nor nucleocapsid antibodies, nor clinical history of COVID-19 disease. Results Long Covid patients had significantly higher cumulative number of IgM positivity of the DNA viruses (18.1% vs 6.7%, p=0.02), and significantly elevated quantitative EBV IgG (420±296 vs 339±282 mg/dL, p=0.033) and Parvo-B19 IgM (0.28±0.29 vs 0.03±0.12 mg/dL, p<0.001) titer as compared to healthy controls. Significantly more patients with long COVID symptoms had an EBV IgG titer above the detection limit as compared with healthy controls (40% vs 28%, p=0.018), suggesting EBV virus reactivation and chronic EBV infection. EBV IgG titer was significantly higher in patients with dominant respiratory symptoms, while elevated Parvo-B19 IgM titer was observed in patients with dominant cardiovascular complaints. In patients with long-COVID syndrome the quantitative EBV IgG titer increased with the time between infection and blood sampling (logarithmic correlation, p=0.011), suggesting the subclinical continuous EBV activation by the SARS-CoV2 RNA virus, while the quantitative Parvo-B19 IgM titer decreased linearly during the observation period. Conclusions In this study of patients with long-COVID syndrome, SARS-CoV-2 infection apparently activated certain types of DNA viruses (EBV, and Parvo-B19), as demonstrated by the significantly higher incidence of cumulative IgM positivity, and elevated EBV IgG and parvovirus-B19 IgM titers, in long-COVID patients compared to healthy controls.

Monitoring of cytomegalovirus, Epstein-Barr virus and adenovirus infections in hematopoietic stem cell transplant recipients

Purpose: Haematopoietic stem cell transplant (HSCT) recipients with iatrogenic immunosuppression are high-risk patients for viral infections. The aim of this study was to investigate the incidence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) infections in HSCT recipients. 
 Materials and Methods: We prospectively monitored 35 patients aged 0-17 years who had allogeneic (n=30) and autologous (n=5) HSCT by quantitative real-time polymerase chain reaction tests for CMV, EBV, and ADV. The monitoring was performed one week before HSCT and weekly for the first 100 days, once a month up to one year after HSCT. In addition, seropositivity for viruses was analysed by Enzyme-Linked Immuno Sorbent Assay a week before transplantation.
 Results: Before transplantation, all 35 (100%) patients who underwent HSCT were CMV IgG positive, 30 (85.7% - 95% CI: 74.1%-97.3%) HSCT recipients were found to be EBV IgG positive. CMV infection was found in 24 (80% - 95% CI: 65.7%-94.3%), ADV infection in 11 (36.7% - 95% CI: 19.4%-53.9%) and EBV infection in 8 (26.7% - 95% CI: 10.8%-42.5%) allogeneic HSCT patients. In this group, CMV DNA viral load in 8 (26.7%) patients, of which one (3.3%) coinfected with EBV DNA and one (3.3%) with ADV DNA, was higher than 1000 copies/mL which was required for pre-emptive treatment. Among 5 autologous HSCT recipients, CMV DNA was detected in 2 patients, EBV DNA in 5 and ADV DNA in 2. Pre-emptive treatment was given to 11 (%31.4 - 95% CI: 16%-46.8%; 6 CMV, 2 EBV, 1 ADV, 1 CMV-EBV and 1 CMV-ADV infection) of 35 patients. Thus, the development of viral disease was prevented in 7 (63.6% - 95% CI: 35.2%-92.1%). Of the total 35 patients, only 2 (5.7% - 95% CI: 0.0%-13.4%) died due to viral infection. 
 Conclusion: Early diagnosis of viral infections by prospective monitoring of viral loads in HSCT patients would be effective in preventing morbidity and mortality by ensuring timely initiation of pre-emptive therapy.

Seroprevalence of Epstein Barr IgG antibody among patients presenting at a tertiary hospital in Port Harcourt, Nigeria

Epstein Barr virus (EBV) has become increasingly recognized as one of the causes of cancer in humans and in Nigeria, its seroepidemiology, has not been fully elucidated. EBV vaccination is not a part of the Expanded Programme of Immunization (EPI) therefore, immunization against the virus is non-existent. This study was conducted to assess the seroprevalence of EBNA IgG antibody in patients in Port Harcourt, Nigeria. Demographic data and sera were collected from 80 consenting patients of different gender and ages from the University of Port Harcourt Teaching Hospital, Rivers State. Their sera were screened for EBV IgG antibodies using enzyme linked immunosorbent assay (ELISA) kit (DIA.PRO Diagnostic Bioprobes, Milano). Of the 80 sera evaluated for EBV Immunoglobulin G antibody, 68 (85%) were positive and 12 (15%) were negative. Seropositivity rate was higher in males (89.3%) than in females (82.9%). Patients within 21-25years had the highest prevalence rate of 87.2%. Age and gender were not significantly associated with the seroprevalence of EBNA IgG antibodies. From the result, the immunity gap in the population is significant. Hence, there is need for vaccination of susceptible individuals in order to ensure the control and elimination of Epstein Barr virus in Nigeria.

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.

Epstein-Barr virus-associated acute pancreatitis: a clinical report and review of literature

BackgroundAcute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults.Case presentationA 3-year-old female was admitted to the “G. Di Cristina” Children's Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered.ConclusionsAcute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected.

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)...

Epidemiology of the Epstein-Barr Virus in Autoimmune Inflammatory Rheumatic Diseases in Northern Brazil.

The present study aimed to describe the seroprevalence infection, Epstein-Barr virus (EBV) genotypes, relate the infection’s profile with the epidemiological and corticotherapy data of patients with Autoimmune inflammatory rheumatic diseases (AIRD). A cross-sectional study was carried out with 139 individuals, 92 with systemic lupus erythematosus (SLE), 27 with rheumatoid arthritis (RA) and 20 with other autoimmune diseases, who were undergoing clinical follow-up in Brazil. Serological tests for the detection of EBV anti-VCA IgM and IgG antibodies, as well as the amplification of a segment of the EBV EBNA-3c gene by conventional PCR were performed to identify the infection and the viral subtype. The Epstein–Barr nuclear antigen 3 (EBNA3C) gene participates of maintenance of viral latency and infected B-lymphocytes immortalization by unclear signaling cascades. The association of active/latent EBV infection with EBV infection profile was assessed by Fisher’s exact test and multiple logistic regression. The seroprevalence of EBV anti-VCA IgG was 100%, while that of anti-VCA IgM was 1.43% (2/139). Active-phase infection was confirmed by the presence of EBV DNA in 40.29% of the population evaluated (56/139), with 45.65% (42/92) in SLE, 25.92% (7/27) in the RA and in 35% (7/20) in other autoimmune diseases. It was observed that individuals with SLE had a higher prevalence of active/lytic EBV infection and that oral corticosteroid therapy at a dose lower than 20 mg/day increased the risk of EBV activity by up to 11 times. Only the presence of EBV-1 was identified. Thus, EBV lytic infection was higher in individuals with SLE when compared to other autoimmune diseases with rheumatologic involvement and the lytic activity of the virus precedes corticosteroid-induced immunosuppression.

CARDIAC TAMPONADE AS A PRESENTING FEATURE OF METASTATIC GI CARCINOMA

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disease. It is characterized by abnormalities in immunoregulation due to a non-malignant proliferation of lymphocytes and secretion of inflammatory cytokines. HLH is typically associated with acquired immunodeficiencies such as in hematopoietic stem cell transplantation. We present a case of a young woman who was treated in our ICU for confirmed HLH which was attributed to an Epstein-Barr virus (EBV) infection that reactivated during her post-transplant immunosuppression. CASE PRESENTATION: A 46-year-old female presented to her primary care physician with gradual dyspnea, spontaneous gum bleeding and lower extremity bruising. She was diagnosed with anemia during her pregnancy. Eventually developed leukopenia and pancytopenia. She was later diagnosed with aplastic anemia and underwent a conditioning regimen prior to peripheral blood stem cell transplantation (PBSCT) with cyclophosphamide, fludarabine, total body irradiation, and rabbit anti-thymocyte globulin (ATG). She had an allogeneic PBSCT from a 10/10 HLA-matched unrelated donor (MUD). Her pre-transplant workup was positive EBV IgG. Donor pre-transplant workup was negative for EBV. Post-transplant immunosuppression consisted of rituximab and tacrolimus. Two months post-transplant, she was admitted for non-neutropenic fevers and diagnosed with Clostridium difficile colitis, acute kidney injury, EBV viremia (>800000 IU/ml), and widespread lymphadenopathy concerning for EBV-associated biopsy proven monomorphic PTLD. She was treated with two doses of Rituximab. Due to worsening encephalopathy, liver function tests and metabolic acidosis, ICU transfer initiated for continuous renal replacement therapy (CRRT). She developed acute respiratory failure and septic shock; was intubated, requiring vasopressors. During her ICU stay, HLH was considered. Bone marrow aspiration and biopsy performed confirmed HLH. High dose dexamethasone therapy was initiated. She also received two doses of Etoposide and a dose of tocilizumab in ICU. She was successfully extubated to high flow nasal cannula. Next Day, given her worsening mental status; Emapalumab (GAMIFANT, Novimmune SA), a fully human anti–IFN-gamma monoclonal antibody for HLH, was administered. Her cognitive function further declined, and she progressed to multiorgan failure and death. DISCUSSION: Aplastic anemia is a hematologic disorder characterized by pancytopenia and bone marrow aplasia. Bone marrow transplantation and immunosuppressive therapy are the modalities currently used, with success rates ranging 60% to 80%. Most treatment options for EBV-HLH have unclear effectiveness in adults. CONCLUSIONS: Despite trying rituximab, dexamethasone, etoposide, tocilizumab and Emapalumab, our transplant patient exhibits a unique and ambiguous intersection of EBV-associated refractory HLH, unresponsive to treatments. REFERENCE #1: Imashuku S, Kuriyama K, Sakai R, Nakao Y, Masuda S, Yasuda N, et al. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center. Med Pediatr Oncol. 2003;41(2):103-9. REFERENCE #2: Fox CP, Shannon-Lowe C, Gothard P, Kishore B, Neilson J, O'Connor N, et al. Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults characterized by high viral genome load within circulating natural killer cells. Clin Infect Dis. 2010;51(1):66-9. REFERENCE #3: Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, et al. Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. N Engl J Med. 2020;382(19):1811-22. DISCLOSURES: No relevant relationships by Padmastuti Akella, source=Web Response No relevant relationships by Saira Imran, source=Web Response No relevant relationships by Aizaaz Khan, source=Web Response No relevant relationships by Kevin Lazo, source=Web Response

Epidemiological risk factors associated with primary infection by Epstein–Barr virus in HIV-1-positive subjects in the Brazilian Amazon region

To identify the prevalence and risk factors for primary Epstein–Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51–15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01–2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12–2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79–1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22–3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1–10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population.

Acute Epstein‐Barr virus associated haemophagocytosis in an Asian female: What is the diagnosis?

Acute <scp>Epstein‐Barr</scp> virus associated haemophagocytosis in an Asian female: What is the diagnosis?

EBV Reactivation Incidence and Severity in Multiple Sclerosis Patients Treated with Autologous Haematopoietic Stem Cell Transplant and Comparing with Aplastic Anaemia Treated with ATG—Single Site Experience

INTRODUCTION: Autologous haematopoietic stem cell transplant(HSCT) with anti-thymocyte globulin (ATG) based conditioning is currently being explored for its efficacy and safety in the treatment of Multiple Sclerosis (MS). Despite increasing experience gained, the procedure still carries significant risk of morbidity. Epstein Barr Virus (EBV) infection and its role in pathogenesis of MS remain undetermined. EBV reactivation and post-transplant lymphoproliferative disorders (PTLD) are well described in allogeneic HSCT and uncommon with auto HSCT for other malignant conditions. Similarly patients with Aplastic anaemia (AA) treated with standard immunosuppressive therapy with ATG/ciclosporin also have increased risk of EBV reactivation but reports of PTLD in this group are very rare. The incidence of clinically significant EBV reactivation in MS patients undergoing HSCT is increasingly recognised. This retrospective study reports rates of EBV reactivation, PTLD incidence and associated clinical sequelae in patients with MS undergoing HSCT as compared with AA patients receiving ATG in our centre.PATIENTS AND METHODS: 36 patients with MS had AHSCT between Feb 2012 and 2017. 35 were conditioned using standard protocol of cyclophosphamide and ATG (2.5mg/kg/day for 3 days), and one with BEAM-ATG. A Comparator group of 40 patients with AA consecutively treated with ATG (40mg/kg/day for 4 days) between Sept 2013 and Nov 2016 was selected. Prior exposure to EBV (EBV IgG) was assessed pre-HSCT. EBV levels monitoring was performed on whole blood samples by quantitative polymerase chain reaction (PCR) as per standard centre protocol. Data was collected retrospectively.RESULTS: All patients had previous EBV exposure. All MS patients with relapsing remitting (n=22) and primary/secondary progressive (n=14) disease were previously treated with median 2 (range, 0-6) disease modifying therapies (DMT) and 23 had at least 1 highly active DMTs. Median age of 43yrs (range, 22-64yrs) versus 52yrs (range, 19-68yrs) in AA group, with 35 patients severe/very severe AA and 5 non-severe treated with ATG. Where follow up data was available there was no difference in EBV reactivation rates (80.6% vs 65% P-0.13). The median time to EBV detection was 28 days (IQ range, 19-41d) vs 11 days (IQ range 5-39 d)with a maximal EBV DNA titre at median of 39 days (IQ range 29.5-49.5d) vs 11.5 days(IQ Range 0-43.5) in MS and AA cohort respectively.Patients were stratified into their maximum level of reactivation based on the amount of EBV copy numbers; 0-100,000 copies, 100,000 - 500,000 copies and >500,000 copies. In MS group (Table 1), 8 patients had symptomatic EBV reactivation; defined as persistent fever, lymphadenopathy and/or B symptoms. 10 (34.5%) MS patients had EBV copies>500,000. 3 of these had findings consistent with PTLD on CT scan, however none had histological diagnosis. 3 other MS patients had worsening neurological symptoms with one presenting as pseudo-relapse. All 6 of these patients were treated with anti-CD20 monoclonal therapy (Rituximab; 375mg/m2 weekly for 4 weeks) with rapid resolution of their symptoms. MS patients were more likely to develop high EBV (>500k) levels (p-0.03) and receiver operating characteristics (ROC) curve analysis (Fig 1) confirmed high EBV levels>500,000 correlate with high sensitivity 85.5%, specificity 82.5% (p-0.004) for clinical events requiring treatment. No significant rituximab related adverse events noted in treated group. As expected, no significant symptomatic EBV and no PTLD events were noted in AA cohort and none required any rituximab therapy for the EBV reactivations.Significantly raised paraproteinaemia was observed in 21 (72.4%) of MS cohort compared to 3 (11.5%) in the AA group (p < 0.01). 3 of the MS cohort experienced paraprotein levels greater than 20 g/L and one (IgG 61.1g/L) developed hyper-viscosity requiring plasma exchange and developed neurological symptoms mimicking a MS relapse.CONCLUSION: EBV reactivation was observed to occur commonly in patients with MS with significant symptoms and risk of neurological sequelae and PTLD events in this group, which is unlike the AA cohort treated with comparable ATG doses. Regular EBV monitoring in first 3 months should be mandated in MS patients undergoing HSCT and we recommend cut-off of 500,000 copy numbers as trigger for consideration of pre-emptive rituximab therapy. [Display omitted] DisclosuresPotter:Jazz: Honoraria; Pfizer: Other: Advisory board. Raj:Celgene: Speakers Bureau; Mallinckrodt: Speakers Bureau; MSD: Speakers Bureau; Bloodwise: Research Funding. Pagliuca:Bluebird: Honoraria; Gilead: Honoraria; Astellas: Consultancy, Speakers Bureau; Pfizer: Honoraria; Merck: Honoraria, Research Funding; Jazz: Honoraria; Basilea: Honoraria.

Identification of Epstein-Barr Virus Related Risk Factors for the Occurrence of Post-Transplant Lymphoproliferative Disorder in Lung Transplant Recipients

<h3>Purpose</h3> Post-transplant lymphoproliferative disorder (PTLD) is the second most common malignancy in solid organ transplantation. Based on recent registry data, ≈ 1.1% of lung transplants (LTx) develop PTLD within the first year. PTLD confers significant morbidity and mortality and has been associated with Epstein-Barr virus (EBV) infection. The threshold for EBV viremia predictive of PTLD is unknown. In the current study we examined risk factors for PTLD development and the relationship between EBV viremia and PTLD in LTx was assessed. <h3>Methods</h3> A single-center, retrospective review of all LTx recipients from 1/1/2009 - 7/31/2019 with EBV viremia was conducted. All patients (pts) with at least one positive EBV PCR test were reviewed for EBV viremia progression and PTLD occurrence. PTLD was confirmed by review of oncology notes, biopsy results, computed tomography and positron emission tomography scans. <h3>Results</h3> One hundred and forty-seven pts were included. Thirty-four (24.8%) underwent work-up for PTLD, of whom ten were diagnosed with PTLD. Median time from transplant to EBV viremia was 368 days (IQR 111-1201) with PTLD diagnosis occurring at a median of 521 days (IQR 150-741) after LTx. The PTLD(+) group had a higher baseline median EBV PCR of 2613 copies/mL (IQR 680-6099) vs 528 copies/mL (IQR 369-930) in PTLD(-) pts and an increased number of positive PCRs; 3.5 (IQR 2-10) vs 1 (IQR 1-2). In patients with EBV IgG data available, (<i>n</i>=66), Donor(+)/Recipient(-) pts were more likely to develop PTLD than other groups, RR = 18.3 (95% CI 3.93, 85.32); p<0.001. A cut-point analysis of EBV viral load determined that pts with a baseline EBV viral load >1930 copies/mL had a significantly higher risk of PTLD development, RR = 31.03 (95 %CI 9.44, 102.02); p<0.001. <h3>Conclusion</h3> EBV mismatch, higher viral loads, and persistence of viremia may be indicative of PTLD development. Patients with an EBV viral load >1930 copies/ml may benefit from closer surveillance.

COVID‐19 associated Kikuchi‐Fujimoto disease

We discuss the case of a 17-year-old male who presented with painful lymphadenopathy, fevers, weight loss, anorexia and a history of preceding anosmia. Histological features on lymph node biopsy were in-keeping with Kikuchi-Fujimoto disease (KFD). We later confirmed SARS-CoV-2 (COVID-19) infection on antibody testing. This case describes an atypical presentation of COVID-19 in a young patient and highlights an association between the virus and this rare disease.

A three year Seroepidemiological and molecular study of Epstein -Barr virus infection among different age groups with hematological malignancies in a Tertiary care centre of North India ( 2017 -2019).

Purpose:Epstein-Barr virus (EBV) is a member of the family Gamma Herpes viridae and is usually implicated in malignancies like non-Hodgkin's lymphoma, Hodgkin's lymphoma and Burkitt's lymphoma. The present study was designed with the aim to estimate the seroprevalence of EBV in people with hematological malignancies and further follow up was planned by viral load quantitation by Real time PCR in positive cases.Methods:The current study was planned for a period of three years and a total of 272 serum samples were tested from patients with hematological malignancies namely; HL, NHL, ALL, CLL. Serological testing was performed for the presence of IgM and IgG antibodies against EBV viral capsid antigen. Sera of the patients found positive for IgM was further subjected to viral DNA extraction and Real Time Quantitative PCR was performed by a commercial kit.Results:The overall seropositivity rate was 89.2% for EBV IgG antibodies and 56.1% for IgM antibodies. The seroprevalence for anti-EBV VCA IgM was found to be highest in the age group <10 years (34.8%) and 11–22 years (20.4%). Of the 109 EBV positive strains by PCR, 27.3% were HL, 35.2% NHL, 24.3% ALL and 13.7% were CLL. The mean viral load was 68.7 × 107 copies/ml DNA.Conclusion:Our study showed a higher seroprevalence and a definite causal relationship of EBV in lymphoma patients. Young adults showed a higher risk of hematological malignancies as compared to elder population. This study can prove to be an essential guide and aid to the primary care physicians in identifying the possible risk factors and seroprevalence in various age groups of EBV malignancy patients for their proper follow up and referral to higher speciality centres.

Self-collected oral flocked swabs to measure prevalence of Epstein-Barr Virus antibodies and DNA amongst university students

Epstein-Barr Virus (EBV) exposure and illness is common in undergraduate university students and may affect academic achievement, social life, and quality of life. We designed a study to measure EBV exposure (EBV-IgG, either Epstein-Barr nuclear antigen 1 (EBNA-1)-IgG or viral capsid antigen (VCA)-IgG) and current viral shedding (EBV-DNA) using self-collected oral swabs among university undergraduate students. Of 184 students enrolled, 129 (70.1%) tested positive for EBV-IgG. Salivopositivity was associated with being in a current relationship, but not with enrollment year. Forty (21.7%) of the participants tested positive for EBV-DNA, which was associated with all symptom scores, including history of sore throat, fever, swollen glands, muscle weakness, and fatigue in the previous 6 months. Our findings suggest that noninvasive, self-collected oral flocked swabs are feasible and potentially valuable for measuring EBV IgG antibodies and DNA.