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Objective: To investigate the diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis (IM). Methods: A total of 135 children with IM as the IM group and 100 healthy volunteers as the healthy group were included in this retrospective study. Peripheral blood lymphocyte subsets marked as CD3+, CD4+, CD8+, CD16 + CD56+, and CD19 + in the peripheral blood were quantified using flow cytometry. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, AUROC curve, and Kappa consistency test to assess the diagnostic value of these markers in IM. Results: The AUROC curve for CD8 + cells and for CD4+/CD8 + ratios both achieved a value of 1 with the sensitivity and specificity of 100% (P<0.001). The Kappa coefficients were 1 for CD8+, CD4+/CD8 + ratios and the combined EBV analysis, indicating a 100% consistency with the clinical diagnosis. Significant differences were also observed in the CD3+, CD4+, CD16 + CD56+, and CD19 + lymphocyte subsets between the IM group and the healthy group (P<0.05). Conclusion: The evaluation of CD8 + and CD4+/CD8 + ratios in peripheral blood lymphocytes represents a significant advancement in the diagnosis of IM. Peripheral blood lymphocyte testing offers a reliable, sensitive, and specific diagnostic tool to enhance the clinical management of children with IM. [ABSTRACT FROM AUTHOR]

Objective: Infectious mononucleosis (IM) or mono is typically caused by primary infection with Epstein-Barr virus (EBV) and may have a months-long, complicated course. We utilized population-based data to add to the limited literature on health care utilization following EBV infection. Methods: The Rochester Epidemiology Project includes medical records for ∼60% of residents living in 27 counties of Minnesota (MN) and Wisconsin (WI). Persons meeting a case definition of recent EBV infection from 1 January 1998 to 31 December 2021 were compared to three persons not meeting the definition, matched on case's sex, age, and index date. Emergency department (ED) visits and hospitalizations in the two groups were compared during 5-years' follow-up divided into three periods (short-term ≤3 months, mid-term >3 months–1 year, long-term >1–5 years). Adjusted hazard ratios (AHR) were estimated to account for the potential influence of confounding variables. Results: In total, 6,423 persons had a recent EBV infection and were matched to 19,269 comparators. The risk of an ED visit was significantly higher among cases in the short-term period (24.3% vs referents: 7.6%, p <.001; AHR = 3.71, 95% CI = 3.41–4.03). Cases also had an increased risk of hospitalization in the short-term (5.2% vs 1.6%: referents, p <.001; AHR = 3.53, 95% CI = 2.94–4.24). For ED visits but not hospitalization, the excess risk persisted into the mid-term follow-up period. Persons without a concurrent clinical diagnosis of IM continued to have an increased risk of hospitalizations up to 1 year after index date (AHR = 1.45, 95% CI = 1.09–1.91) and an increased risk of ED visits up to 5 years after the index date (AHR = 1.29, 95% CI = 1.14–1.46). Conclusion: There is a substantial short- and mid-term increased risk of serious health care encounters associated with recent EBV infection. Mid- and long-term risks are increased in patients who do not have a concomitant diagnosis of IM. [ABSTRACT FROM AUTHOR]

Introduction The U.S. Military members experiencing combat-related injuries have a higher chance of developing infections by multidrug-resistant (MDR) bacteria at admission to military hospitals. MDR wound infections result in higher amputation rates and greater risks for subsequent or chronic infections that require readmission or extended stay in the hospital. Currently, there is no FDA-clear, deployable early diagnostic system for suitable field use. We are reporting our efforts to improve a previously developed Rapid Label-free Pathogen Identification (RAPID) system to detect viable MDR bacteria in wound infections and perform antibiotic susceptibility testing (AST). Specifically, we added multiplex and automation capability and significantly simplified the sample preparation process. A functional prototype of the improved system was built, and its performance was validated using a variety of lab-prepared spiked samples and real-world samples. Materials and Methods To access the baseline performance of the improved RAPID system in detecting bacteria presence, we selected 17 isolates, most of them from blood or wound infections, and prepared mono-strain spiked samples at 104 to 106 cfu/mL concentration. These samples were processed and analyzed by the RAPID system. To demonstrate the AST capability of the system, we selected 6 strains against 6 different antibiotics and compared the results from the system with the ones from the gold standard method. To validate the system's performance with real-world samples, we first investigated its performance on 3 swab samples from epicutaneous methicillin-resistant Staphylococcus aureus –exposed mouse model. The AST results from our system were compared with the ones from the gold standard method. All animal experiments were approved by the Johns Hopkins University Animal Care and Use Committee (Protocol No. MO21M378). Then, we obtained swab samples from 7 atopic dermatitis (AD) patients and compared our AST results with the ones from the gold standard method. The human subject protocol was approved by the Johns Hopkins Medicines Institutional Review Boards (Study No. CR00043438/IRB00307926) and by USAMRDC (Proposal Log Number/Study Number 20000251). Results High-quality data were obtained from the spiked samples of all 17 strains. A quantitative analysis model built using these data achieved 94% accuracy in predicting the species ID in 8 unknown samples. The AST results on the spiked samples had shown 100% matching with the gold standard method. Our system successfully detects the presence/absence of viable bacteria in all 3 mouse and 7 AD patient swab samples. Our system shows 100% and 85.7% (6 out of 7) accuracy when compared to the oxacillin susceptibility testing results for the mouse and the AD patient swabs, respectively. Conclusions Our system has achieved excellent performance in detecting viable bacteria presence and in performing AST in a multiplex, automated, and easy-to-operate manner, on both lab-prepared and real samples. Our results have shown a path forward to a rapid (sample-to-answer time ≤3 hours), accurate, sensitive, species-specific, and portable system to detect the presence of MDR combat-related wound infections in the field environment. Our future efforts involve ruggedizing the RAPID system and evaluating performance under relevant environmental conditions. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) reactivation in COVID-19 patients has been reported, but studies on its clinical significance are lacking. We herein report the occurrence of infectious mononucleosis (IM) due to EBV reactivation in a 60-year-old man with rheumatoid arthritis being treated with methotrexate and tocilizumab. The patient presented with a fever and tested positive for COVID-19. Laboratory findings revealed an increased atypical lymphocyte count, decreased platelet count, and elevated liver enzyme levels. Flow cytometry showed predominant expansion of reactive T cells. EBV reactivation was confirmed using real-time polymerase chain reaction. The patient was treated with remdesivir, and clinical improvement was observed after 10 days of treatment. Follow-up showed a gradual decrease in the EBV-DNA load with no recurrence of atypical lymphocytes. These findings suggest that COVID-19 in immunocompromised patients may lead to unexpected EBV reactivation and IM, even for patients outside the age at which IM is likely to occur. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions. Materials and Methods: The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality. Results: Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (hazard ratio [HR], 5.320; 95% confidence interval [CI], 3.208 to 8.820; p < 0.001) and NPC (HR, 7.116; 95% CI, 1.617 to 31.314; p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR, 2.225; 95% CI, 1.858 to 2.663; p < 0.001). Conclusion: This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures. [ABSTRACT FROM AUTHOR]

Background: Exanthematous drug eruption and infectious mononucleosis (IM) are both exanthematous diseases. Current research on exanthematous drug eruption and IM mainly targets identifying these disorders, the resulting differences at the metabolism level have not yet been systematically analyzed. Materials and methods: A total of 30 cases of exanthematous drug eruption and IM, 10 patients without exanthema and 10 healthy volunteers were enrolled, 3 mL of fasting venous blood was collected, the serum metabolite content was detected by gas chromatography‐mass spectrometry metabolomics. Results: A total of 165 metabolites were identified, exhibiting significant differences in plasma metabolic trends between exanthematous drug eruption and IM, and pinpointed 28 potential biomarkers. Notable changes were seen in the metabolic activities of the pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA‐cycle), and galactose metabolism, characterized by increased levels of gluconate, gluconolactone, glucose, galactaric acid, and mannose, along with decreased amounts of pyruvic acid, succinic acid, malic acid, and glycerol, indicating an impairment in the exanthematous drug eruption group's capacity to endure oxidative stress and regulate energy metabolism. In contrast to its medication without rash counterpart, the exanthematous drug eruption group's plasma displayed distinct metabolic routes, predominantly in the processing of arginine and proline, along with the TCA. This resulted in a marked reduction in urea levels and a rise in pyruvate, citrate, and ornithine, indicating hypoxic stress as the primary cause of these rashes. In contrast to the healthy control group, the IM group showed 26 potential biomarkers, marked by increased levels of ketoglutaric acid, malic acid, pyruvic acid, and oxoglutaric acid, and reduced amounts of glutamine, galacturonic acid, arachidonic acid, trimethylphosphonic acid ester, gluconolactone, and indole acetic acid. Mainly, the metabolic pathways included the TCA, breaking down alanine, aspartate and glutamate metabolism, and the processing of D‐glutamine and D‐glutamate metabolism, underscoring the body's crucial role in generating energy and inflammatory agents through the citric acid cycle. Conclusions: The comparison of serum metabolomic features of exanthematous drug eruptions and IM outlines a unique pattern closely related to the differences in the pathogenesis of these two exanthematous diseases. [ABSTRACT FROM AUTHOR]

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Introduction: Epstein-Barr virus (EBV) is an oncogenic human herpesvirus associated with ~350,000 cases of lymphoid and epithelial malignancies every year, and is etiologically linked to infectious mononucleosis and multiple sclerosis. Despite four decades of research, no EBV vaccine candidate has yet reached licensure. Most previous vaccine attempts focused on a single viral entry glycoprotein, gp350, but recent data from clinical and pre-clinical studies, and the elucidation of viral entry mechanisms, support the inclusion of multiple entry glycoproteins in EBV vaccine design. Methods: Here we generated a modified vaccinia Ankara (MVA)-vectored EBV vaccine, MVA-EBV5-2, that targets five EBV entry glycoproteins, gp350, gB, and the gp42gHgL complex. We characterized the genetic and translational stability of the vaccine, followed by immunogenicity assessment in BALB/c mice and rhesus lymphocryptovirus-negative rhesus macaques as compared to a gp350-based MVA vaccine. Finally, we assessed the efficacy of MVA-EBV5-2-immune rhesus serum at preventing EBV infection in human CD34+ hematopoietic stem cell-reconstituted NSG mice, under two EBV challenge doses. Results: The MVA-EBV5-2 vaccine was genetically and translationally stable over 10 viral passages as shown by genetic and protein expression analysis, and when administered to female and male BALB/c mice, elicited serum EBV-specific IgG of both IgG1 and IgG2a subtypes with neutralizing activity in vitro. In Raji B cells, this neutralizing activity outperformed that of serum from mice immunized with a monovalent MVA-vectored gp350 vaccine. Similarly, MVA-EBV5-2 elicited EBV-specific IgG in rhesus macaques that were detected in both serum and saliva of immunized animals, with serum antibodies demonstrating neutralizing activity in vitro that outperformed serum from MVA-gp350-immunized macaques. Finally, pre-treatment with serum from MVA-EBV5-2-immunized macaques resulted in fewer EBV-infected mice in the two challenge experiments than pretreatment with serum from pre-immune macaques or macaques immunized with the monovalent gp350-based vaccine. Discussion: These results support the inclusion of multiple entry glycoproteins in EBV vaccine design and position our vaccine as a strong candidate for clinical translation. [ABSTRACT FROM AUTHOR]

Introduction: Epstein-Barr virus (EBV) infection, with a global prevalence exceeding 95%, typically manifests in children as infectious mononucleosis. However, clinical practice frequently encounters diverse atypical presentations characterized by multisystem involvement, often resulting in an unfavorable clinical course. Our objective is to describe the clinical manifestations and results of EBV infection in a tertiary pediatric hospital in Mexico. Method: An observational, transversal, retrospective, and descriptive study that included a systematic review of medical records (2012-2022) of patients under 18 years of age with detectable EBV particles in peripheral blood. Results: The study included 26 patients with a median age of 5 years and a male predominance of 53.8%. Predominant symptoms were fever (85%) and lymphadenopathy (35%). Sixty-five percent had severe and atypical manifestations, including pneumonia and hepatic, hematologic-oncologic, and autoimmune diseases. Anemia, thrombocytopenia and leukopenia were common, with lymphocytosis in 19% of cases. The median EBV viral load was 2816 copies/mL (range: 555-355,500 copies/mL). Four deaths related to EBV infection were reported. Viral load in these cases also varied widely from 594 to 121,000 copies/mL. Supportive care was administered to 85% of patients, while others received antiviral treatment, steroids, and rituximab. Conclusion: Atypical manifestations were common, especially in children with multisystem involvement. EBV should be considered as a potential contributor to a diverse spectrum of clinical presentations, emphasizing the need for comprehensive evaluation and awareness in clinical diagnosis. [ABSTRACT FROM AUTHOR]

Diseases of the tonsils and adenoids are extremely common in children and make up a significant part of the paediatric ENT surgeon's practice, as well as presenting frequently to paediatric and primary care teams. The majority of adenotonsillar pathology in children is either infective or obstructive in nature. This article discusses the anatomy and pathophysiology of acute and chronic adenotonsillar disease and discusses how to evaluate a child with suspected adenotonsillar pathology clinically, in both the outpatient and emergency scenario. Surgical management and the adenoidectomy and tonsillectomy techniques are described. The current multidisciplinary working group guidelines regarding surgery for obstructive sleep apnoea in children are also highlighted. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate the diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis (IM). Methods A total of 135 children with IM as the IM group and 100 healthy volunteers as the healthy group were included in this retrospective study. Peripheral blood lymphocyte subsets marked as CD3+, CD4+, CD8+, CD16 + CD56+, and CD19 + in the peripheral blood were quantified using flow cytometry. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, AUROC curve, and Kappa consistency test to assess the diagnostic value of these markers in IM. Results The AUROC curve for CD8 + cells and for CD4+/CD8 + ratios both achieved a value of 1 with the sensitivity and specificity of 100% (P

Vasculitis of the retina and the optic nerve is one of the most complex, rare and challenging issues in clinical ophthalmology. Managing patients with this diagnosis is difficult because practical ophthalmologists lack sufficient experience, clinical manifestations and courses of the disease are versatile and technical means of full-scale diagnostics and observation, including fluorescein angiography are limited. The report illustrates a particular case of optic nerve vasculitis in a young female patient. We assumed that an infectious mononucleosis that she had experienced led to immune dysfunction and the development of autoimmune vasculitis of the optic nerve. An immunosuppressive therapy was prescribed, which allowed achieving a good clinical result.

This clinical case describes a rare clinical complication of infectious mononucleosis associated with Epstein-Barr virus in a 19-year-old patient. The current literature sources; medical history; examination data and discharge epicrisis of the patient are analyzed. Rupture of the spleen is an extremely rare complication that develops in 1% of patients against the background of infection. At the same time; the diagnosis of the complication is not very difficult – it is necessary to conduct ultrasound of the abdominal organs in dynamics in the event of a rupture clinic (critical days of the disease are especially important – 10-20 days). But due to its rarity; many clinicians forget about the possibility of developing this complication. The main purpose of the work is to attract attention and alertness to the potentially fatal complication of infectious mononucleosis.

Abstract Background Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM). Methods We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset). Results All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (r s = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells. Conclusions All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.

Objective: To evaluate the effects of ganciclovir combined with recombinant human interferon on clinical efficacy and immune function of children with infectious mononucleosis(IM). Methods: This was a retrospective study. Children (n=120) with IM hospitalized in Beijing Children’s Hospital Affiliated to Capital Medical University Baoding Hospital from January 2020 to January 2022 were selected and randomly divided into study group and control group((n=60). Patients in the control group were treated with ganciclovir by intravenous infusion, and patients in the study group were given ganciclovir+recombinant human interferon-α1b. The time for eliminating clinical symptoms, the levels of inflammatory cytokines, immune function condition and T-lymphocyte subsets between the two groups were compared and analyzed. Results: After treatment, the time for body temperature returned to normal, time for recovery from cervical lymphadenopathy, time for recovery from hepatosplenomegaly and time for disappearance of angina and oral mucosal congestion in the study group were significantly shorter than those in the control group(p= 0.00); after treatment, the levels of TNF-a and IL-6 in the study group were significantly lower than those in the control group; the indexes of CD3+ and CD8+ in the study group were significantly lower than those in the control group; after treatment, the levels of CD4+ and CD4+ /CD8+ in the study group were significantly higher than those in the control group. Conclusion: Ranciclovir combined with recombinant human interferon-α1b, rapid improvements of clinical symptoms, significantly decreased inflammatory cytokines, improved T-lymphocyte function and no significant increase in adverse drug reactions were found in children with IM. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pelvic inflammatory disease associated with cytomegalovirus infection in immunocompetent adults might be difficult to diagnose because of the rarity and relatively inconspicuous symptoms of infectious mononucleosis. Even if the main complaint is lower abdominal pain, careful search for symptoms latent outside the abdomen could lead to the diagnosis. [ABSTRACT FROM AUTHOR]

Spontaneous splenic rupture (SSR) is a relatively rare but potentially lethal complication of infectious mononucleosis (IM). While SSR is extremely rare in patients with proven IM, it is the most lethal complication of the infection (9% mortality rate) and can present completely asymptomatically or with abdominal pain and hemodynamic instability. As adolescents and young adults are the most affected population group, with this case report, we intend to raise the vigilance of any doctor treating those patients in the emergency department. We present the case of a 16-year-old patient with an atraumatic splenic rupture and hemoperitoneum secondary to an Epstein–Barr virus (EBV) infection. The patient underwent an exploratory laparotomy, and a splenectomy was performed. This case demonstrates that, even if SSR in patients with IM is extremely rare, it should always be considered in a patient with a relevant clinical presentation. [ABSTRACT FROM AUTHOR]

Background: Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM). Methods: We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset). Results: All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (rs = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells. Conclusions: All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity. [ABSTRACT FROM AUTHOR]

Introduction: infectious mononucleosis is an infection caused by various viruses, the most common being the Epstein-Barr Virus, which affects adolescents and young adults. Only 10% of pediatric patients are symptomatic and not all present the typical triad of the disease. Clinic case: this report presents a case of infectious mononucleosis due to Epstein-Barr Virus, which highlights a course of disease in an unusual age group, with compromised liver function that resolves with symptomatic treatment. Conclusions: patients with infectious mononucleosis due to Epstein-Barr Virus should undergo long-term follow-up to identify complications early.

BackgroundBilateral optic neuritis associated with optic disc swelling is a common feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, extensive deep retinal haemorrhages have not been described in the context of MOG-associated optic neuritis. Here, we report a case of infectious mononucleosis with marked binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages in the presence of MOGAD.Case reportA 39-year-old Chinese woman presenting with subacute binocular vision reduction with no light perception was diagnosed with MOGAD. Fundus examination revealed the presence of binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages with severe optic disc swelling greater in the right eye than in the left and dilated and tortuous retinal venules. The patient tested positive for the Epstein–Barr virus (EBV) antigen (595 U/mL) and the EBV capsid antigen (>750 U/mL). She had a fever and right upper quadrant abdominal pain, and a doctor determined splenomegaly 1 week before the onset of orbital pain and decreased vision acuity. Medical history and laboratory tests indicated the presence of concurrent infectious mononucleosis. Other investigational indicators of retinal haemorrhages, including hypertension, diabetes mellitus, vascular disease, systemic lupus erythematosus, metabolic disease, and renal or liver dysfunction, were absent.DiscussionThis case suggests that retinal haemorrhage is a possible complication of infectious mononucleosis in the presence of MOGAD.

IntroductionEpstein-Barr virus (EBV) is an oncogenic human herpesvirus associated with ~350,000 cases of lymphoid and epithelial malignancies every year, and is etiologically linked to infectious mononucleosis and multiple sclerosis. Despite four decades of research, no EBV vaccine candidate has yet reached licensure. Most previous vaccine attempts focused on a single viral entry glycoprotein, gp350, but recent data from clinical and pre-clinical studies, and the elucidation of viral entry mechanisms, support the inclusion of multiple entry glycoproteins in EBV vaccine design.MethodsHere we generated a modified vaccinia Ankara (MVA)-vectored EBV vaccine, MVA-EBV5-2, that targets five EBV entry glycoproteins, gp350, gB, and the gp42gHgL complex. We characterized the genetic and translational stability of the vaccine, followed by immunogenicity assessment in BALB/c mice and rhesus lymphocryptovirus-negative rhesus macaques as compared to a gp350-based MVA vaccine. Finally, we assessed the efficacy of MVA-EBV5-2-immune rhesus serum at preventing EBV infection in human CD34+ hematopoietic stem cell-reconstituted NSG mice, under two EBV challenge doses.ResultsThe MVA-EBV5-2 vaccine was genetically and translationally stable over 10 viral passages as shown by genetic and protein expression analysis, and when administered to female and male BALB/c mice, elicited serum EBV-specific IgG of both IgG1 and IgG2a subtypes with neutralizing activity in vitro. In Raji B cells, this neutralizing activity outperformed that of serum from mice immunized with a monovalent MVA-vectored gp350 vaccine. Similarly, MVA-EBV5-2 elicited EBV-specific IgG in rhesus macaques that were detected in both serum and saliva of immunized animals, with serum antibodies demonstrating neutralizing activity in vitro that outperformed serum from MVA-gp350-immunized macaques. Finally, pre-treatment with serum from MVA-EBV5-2-immunized macaques resulted in fewer EBV-infected mice in the two challenge experiments than pretreatment with serum from pre-immune macaques or macaques immunized with the monovalent gp350-based vaccine.DiscussionThese results support the inclusion of multiple entry glycoproteins in EBV vaccine design and position our vaccine as a strong candidate for clinical translation.

Splenic rupture in haemodynamically unstable patients has traditionally been managed with splenectomy. This case report discusses the successful management of atraumatic splenic rupture, a rare but life-threatening complication of Epstein-Barr virus (EBV) infection, in a hemodynamically unstable patient. The patient, diagnosed with infectious mononucleosis (IM) secondary to EBV, presented with severe abdominal pain and a syncopal episode. Imaging revealed an American Association for the Surgery of Trauma (AAST) grade III splenic injury, which was subsequently upgraded to a grade IV injury on repeat imaging. The patient's condition deteriorated even with initial resuscitation, leading to splenic angioembolization. The procedure was successful and the patient was discharged after 5 days. This case highlights the efficacy of splenic artery embolization (SAE) in haemodynamically unstable patients with atraumatic splenic rupture, particularly in centers with interventional radiology resources, offering an alternative to splenectomy and its associated complications.

Abstract In this study, Raman spectroscopy is applied to trace lymphocytes activation following contact with the Epstein–Barr virus (EBV) of the herpesvirus family. The biomarker of cell activation is found to be the 520 cm−1 band, indicating formation of immunoglobulins. The blood samples are obtained from patients diagnosed with infectious mononucleosis and treated at the University Hospital in Kraków. The lymphocytes’ Raman spectra are collected using a mapping technique, exciting samples with a 514.5 nm line of Ar + laser. Measurements are performed on the 1st, 4th, 6th, 12th and 30th day of hospitalization, until the patient has recovered. The highest intensity of the immunoglobulin marker is observed on the 4th day of hospitalization, while the results of the blood count of patients show the greatest increase in the number of lymphocytes at the beginning of hospitalization. No activated lymphocytes were observed in the blood of healthy volunteers. Some information is provided by the evaluation of B-cell activation by estimating the activated areas in the cells, which are determined by the presence of the Ig marker. The 900 cm−1 band and band around 1450 cm−1 are also analyzed as markers of the presence of the latent membrane protein, LMP2A (and 2B), of the EBV viral protein. The anomalous degree of depolarization observed in B-cells in the course of EBV infection appears to be due to the influence of a virus protein, disrupting BCR signal transduction.

Background: The goal was to study the difference of virological, immunologic, and inflammatory indicators between Epstein-Barr associated infectious mononucleosis (EBV-IM) and EBV associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to explore the evaluation indicators for monitoring the therapeutic efficacy of EBVHLH. Methods: Twenty children with EBV-IM (IM group) and 10 children with EBV-HLH (HLH group) were selected. Virology indicators were detected; the absolute count of lymphocyte, and lymphocyte subsets were detected; the levels of immunoglobulin and ferritin were assayed. Results: Compared to the IM group, the HLH group showed a decrease in EBV-specific VCA-IgM antibody levels (U = 29.0, p = 0.006) and an increase in EBV-specific NA-IgG antibody levels (U = 17.0, p = 0.001), while there was no significant difference in EB-DNA loads (t = 0.417, p = 0.680). The counts of lymphocytes, and various lymphocyte subsets in the HLH group were lower than those in the IM group. Inflammatory markers in the HLH group were significantly higher than those in IM group. Dynamic monitoring of virological, immunological, and inflammatory indicators in HLH patients during treatment showed that EBV DNA gradually decreased in patients with good prognosis. Inflammatory indicators significantly decreased and returned to normal, lymphocyte count significantly increased and returned to normal during treatment. However, patients with poor prognosis showed rebound increase in EBV DNA and inflammatory indicators in the later stage of treatment, while lymphocyte count further decreased with the recurrence of the disease. Conclusions: Exhausted and damaged immune function in host by persistent stimulation of EB viral antigen is one of the main pathogeneses of EB-HLH. Lymphocyte count and serum ferritin level are effective indicators to monitor the therapeutic efficacy during the treatment to HLH. [ABSTRACT FROM AUTHOR]

Background: Epstein–Barr virus (EBV) is thought to be a necessary causative agent in the development of multiple sclerosis (MS). Infectious mononucleosis (IM), which occurs up to 70% of adolescents and young adults with primary EBV infection, appears to be a further risk factor but few studies have been highly powered enough to explore this association by time since IM diagnosis. Objective: The objective was to quantify the risk of MS in individuals with IM compared with the general population, with particular focus on time since IM diagnosis. Methods: In this retrospective cohort study using English national Hospital Episode Statistics from 2003 to 2023, patients with a hospital diagnosis of IM were compared with the general population for MS incidence. Results: MS incidence in patients with IM was nearly three times higher than the general population after multivariable adjustment (adjusted hazard ratio = 2.8, 95% confidence interval (CI = 2.3–3.4), driven by strong associations at long time intervals (>5 years) between IM diagnosis and subsequent MS diagnosis. Conclusion: While EBV infection may be a prerequisite for MS, the disease process of IM (i.e. the body's defective immune response to primary EBV infection) seems to be, in addition, implicated over the long term. [ABSTRACT FROM AUTHOR]

Cholestatic hepatitis is a rare complication of acute Epstein-Barr virus (EBV) infection. Here, we presented a case of acute cholestatic hepatitis secondary to acute infectious mononucleosis, who presented with complaints of abdominal pain, yellowing of the eyes and body, itching, widespread body pain, fever, nausea and vomiting. It was emphasized that EBV infection should also be considered in the differential diagnosis of cholestatic hepatitis etiology. [ABSTRACT FROM AUTHOR]

In this study, Raman spectroscopy is applied to trace lymphocytes activation following contact with the Epstein–Barr virus (EBV) of the herpesvirus family. The biomarker of cell activation is found to be the 520 cm−1 band, indicating formation of immunoglobulins. The blood samples are obtained from patients diagnosed with infectious mononucleosis and treated at the University Hospital in Kraków. The lymphocytes’ Raman spectra are collected using a mapping technique, exciting samples with a 514.5 nm line of Ar + laser. Measurements are performed on the 1st, 4th, 6th, 12th and 30th day of hospitalization, until the patient has recovered. The highest intensity of the immunoglobulin marker is observed on the 4th day of hospitalization, while the results of the blood count of patients show the greatest increase in the number of lymphocytes at the beginning of hospitalization. No activated lymphocytes were observed in the blood of healthy volunteers. Some information is provided by the evaluation of B-cell activation by estimating the activated areas in the cells, which are determined by the presence of the Ig marker. The 900 cm−1 band and band around 1450 cm−1 are also analyzed as markers of the presence of the latent membrane protein, LMP2A (and 2B), of the EBV viral protein. The anomalous degree of depolarization observed in B-cells in the course of EBV infection appears to be due to the influence of a virus protein, disrupting BCR signal transduction. [ABSTRACT FROM AUTHOR]

Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively. [ABSTRACT FROM AUTHOR]

Key Clinical Message Pelvic inflammatory disease associated with cytomegalovirus infection in immunocompetent adults might be difficult to diagnose because of the rarity and relatively inconspicuous symptoms of infectious mononucleosis. Even if the main complaint is lower abdominal pain, careful search for symptoms latent outside the abdomen could lead to the diagnosis.

Key Clinical Message In patients with symptoms of viral infection and marked thickening of the gallbladder wall, it is important to suspect acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis. Abstract A 35‐year‐old Japanese man presented with fever, abdominal right upper quadrant pain, and liver dysfunction. Positive immunoglobulin M and ‐G antibodies and negative nuclear antigen for Epstein–Barr virus were observed. Abdominal ultrasonography revealed a markedly thickened gallbladder wall. Acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis was diagnosed.

The purpose of the study was to evaluate the clinical and laboratory features of infectious mononucleosis with liver damage in children hospitalized in an infectious diseases hospital.Materials and methods. A comparative retrospective study was conducted from January 2018 to June 2021. 200 Medical records of an inpatient were selected by random sampling. Inclusion criteria: age from 1 to 17 years, clinical presentation of infectious mononucleosis, absence of severe concomitant pathology. All patients underwent a standard laboratory examination, additionally determined the DNA of herpes viruses in the blood by PCR. Depending on the presence of cytolysis syndrome (ALT level > 31 U/l), all patients were divided into 2 groups: children with hepatic manifestations of IMN – 80 patients (40%) and without them – 120 (60%). Statistical analysis of the obtained results was carried out using the statistical program Statistica 8 (USA).Results. Epstein – Barr virus was the cause of the development of IMN clinic in 59% (118/200) of cases of monoinfection and in 14.5% (29/200) in combination with other herpesviruses. All participants in the study had moderate disease. An increase in the level of alanine aminotransferase (ALT) above 150 U/L was recorded in 9.5% (19/200) of the examined, no one had more than 1000 U/L, the median was 72.5 (MKR 48–138.5) U/L. Liver damage was more often recorded in children older than 3 years, girls predominated (53.8%, p = 0.017). In patients with liver damage, the following were recorded: moderately severe fever and lymphadenopathy (p < 0.05), hepatosplenomegaly (p < 0.001), lymphocytic leukocytosis (p < 0.05), thrombocytopenia (p < 0.001), atypical mononuclear cells were detected more often (p < 0.001), less often an increase in the level of CRP (p = 0.008).Conclusions. Our study showed that liver damage in IMN is registered in 40% of hospitalized children. Obviously, children with moderate forms of IMN need laboratory and instrumental monitoring of the state of the hepatobiliary system and appropriate correction of therapy.

Infectious mononucleosis is an acute anthroponotic disease that develops as a result of human infection with viruses of the Herpesviridae family: Epstein – Barr virus (EBV), cytomegalovirus (CMV), herpes viruses of the 6th (HHV-6) and 7th types.The aim of our work was to study the clinical features and laboratory parameters of the course of infectious mononucleosis in patients of three age groups.Material and methods. A retrospective analysis of 156 medical records of patients who were on outpatient treatment by an infectious disease specialist at Clinical Medicine Center MedMix was carried out. Patients were divided into three categories according to the age criterion: the first group from 0 to 5 years consisted of 58 (37.2 %) children, the second group was represented by persons from 5 to 18 years old – 58 (37.2 %), the third group was formed by patients from 18 to 53 years old – 40 (25.6 %) people.Results and its discussion. Among children aged 0 to 5 years, boys (67.2 %) more frequently fell sick, and in the group from 18 to 53 years, females (70 %) were more likely to have the disease. Clinical symptoms such as generalized lymphadenopathy (82.7 %), nasopharyngeal lesions (79.3 %) and changes in the general blood test (86.2 %) were most frequently detected in children aged up to 5 years, while fever (81 %) and oropharyngeal lesions (74.1 %) were most frequently detected in patients aged from 5 to 18 years. Liver damage with the development of acute induced viral hepatitis was recorded in all age groups (24.1, 27.6 and 30 %). EBV infection was most frequently diagnosed among children aged from 5 to 18 years and persons aged from 18 to 53 years (in 62.1 and 70 % of cases, respectively, p < 0.05). Mixed infection with the combination of VEB + CMV + HHV-6 was significantly more frequent in children under 5 years of age (34.5 %; p < 0.05).Conclusions. In childhood, the clinical manifestations of infectious mononucleosis were more pronounced. Such intense course of the disease caused frequent visits to an infectious disease specialist and diagnostics with the establishment of an etiological agent. The dominance of EBV infection in the development of infectious mononucleosis in all groups was established. However, at the age up to 5 years, the most common mixed infections were the following combinations: EBV + CMV, EBV + HHV-6, EBV + CMV + HHV-6 and CMV + HHV-6.

Key Clinical Message: In patients with symptoms of viral infection and marked thickening of the gallbladder wall, it is important to suspect acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis. A 35‐year‐old Japanese man presented with fever, abdominal right upper quadrant pain, and liver dysfunction. Positive immunoglobulin M and ‐G antibodies and negative nuclear antigen for Epstein–Barr virus were observed. Abdominal ultrasonography revealed a markedly thickened gallbladder wall. Acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis was diagnosed. [ABSTRACT FROM AUTHOR]

The three primary differential diagnoses for a patient with systemic and hematological involvements (fever, lymphadenopathy, and hepatosplenomegaly), skin rashes, and sore pharynx are infections, connective tissue diseases, and malignancies. In this case report, we discuss possible illusory similarities between these categories that can aid in the diagnostic workup of primary care physicians. Practical Implications. The clinical course of (Infections mononncleosis, MI) patients with and their histopathological data rarely differ; Therefore, early testing for IM caused by EBV is recommended. This article will help physicians face similar cases

Primary Epstein‐Barr virus (EBV) infection occasionally causes EBV‐infectious mononucleosis (EBV‐IM) and EBV‐hemophagocytic lymphohistiocytosis (EBV‐HLH). Although EBV‐IM is mostly mild and self‐limiting, EBV‐HLH is a life‐threatening disease characterized by excessive immune activation. However, the pathogenesis of EBV‐HLH is yet to be fully elucidated. A diagnostic biomarker for EBV‐HLH is desirable because early diagnosis and treatment are critical for the effective management of patients. In this study, the proteomic profiling of plasma was performed using liquid chromatography‐mass spectrometry to identify proteins specific to EBV‐IM and EBV‐HLH. Furthermore, pathway analysis was performed for the proteins upregulated in patients with EBV‐IM and EBV‐HLH. Compared to healthy controls, 63 and 18 proteins were upregulated in patients with EBV‐IM and EBV‐HLH, respectively. Pathway and process enrichment analyses revealed that the complement system was the most enriched category of upregulated proteins in EBV‐IM, whereas proteins related to immune effector processes were the most enriched in EBV‐HLH. Among the 18 proteins upregulated in EBV‐HLH, seven were exclusive to EBV‐HLH. These specific proteins were associated with three pathways, and apolipoprotein E was commonly found in all the pathways. Proteomic analysis may provide new insights into the host response to EBV infection and the pathogenesis of EBV‐related diseases. [ABSTRACT FROM AUTHOR]

This study examined the distinctions between multisystem inflammatory syndrome associated with coronavirus disease 2019, Kawasaki disease, and infectious mononucleosis. These three inflammatory disorders have commonalities according to clinical and laboratory results, particularly in relation to eosinophil levels. In this retrospective, single-center study, we documented the examination records (acute phase reactants and complete blood count) and clinical and cardiological findings of 130 patients diagnosed with multisystem inflammatory syndrome, Kawasaki disease, and infectious mononucleosis. These patients were treated and received follow-up care in our hospital from March 12, 2020, to September 13, 2022, as per the hospital records. Statistical analyses were performed using NCSS 2007, version 1 software. Eosinopenia was more prevalent in children with multisystem inflammatory syndrome than in those with Kawasaki disease, who showed normal or elevated eosinophil counts. The eosinophil counts in patients with infectious mononucleosis typically fell within the normal range. Our study found no correlation between the eosinophil counts and cardiac involvement in pediatric patients with either condition. These findings indicate a higher prevalence of eosinopenia in patients with multisystem inflammatory syndrome, irrespective of cardiac involvement, than in those with Kawasaki disease. Despite similarities in clinical findings, Kawasaki disease and multisystem inflammatory syndrome in children necessitate further studies for distinct characteristic elucidation. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) is a DNA virus that infects almost all adults. It is usually asymptomatic or causes a self-limiting illness but rarely can present serious complications. Case Description: We hereby report the case of a 28-year-old female who presented to us with a history of fever with malaise and an episode of Malena. She was hemodynamically stable. She had thrombocytopenia, elevated transaminases, and polyserositis on workup. She was evaluated for the same and found to be EBV positive with remaining infective and autoimmune workup within normal limits. Her symptoms persisted for a total duration of approximately 3 weeks before she became asymptomatic and was discharged. Conclusion: This case highlights that EBV should be considered as a differential diagnosis in such cases with atypical presentations especially in young adults. [ABSTRACT FROM AUTHOR]

Introduction: Infectious mononucleosis (IM) is a common infectious disease in children mainly caused by Epstein–Barr virus (EBV) infection, followed by abnormal immune response, and resulting in serious complications. However, there are few clinical analyses of immune responses in children with IM at different stages. Methods: This study combined EBV serological test and EBV DNA test to diagnose the infection status of children with IM, and the infection status was divided into primary acute IM infection (AIM), primary late IM infection (LIM) and reactivation IM infection (RIM). Results: The results revealed that the absolute numbers of leukocytes and CD8+ T lymphocytes in primary IM infection were significantly higher than those in reactivation infection, while the frequencies of CD4+ T lymphocytes and B cells were significantly lower than those in reactivation infection. In addition, the activities of ALT, AST, α‐HBDH and LDH in liver function indicators in primary infection were significantly increased compared with reactivation infection. Similarly, the EBV DNA levels of the primary infection were significantly higher than that of the reactivation infection. Conclusion: There are differences in immune response at different stages of infection, which can provide guidance for effective treatment in children with IM infection. [ABSTRACT FROM AUTHOR]

The three primary differential diagnoses for a patient with systemic and hematological involvements (fever, lymphadenopathy, and hepatosplenomegaly), skin rashes, and sore pharynx are infections, connective tissue diseases, and malignancies. In this case report, we discuss possible illusory similarities between these categories that can aid in the diagnostic workup of primary care physicians. Practical Implications. The clinical course of (Infections mononncleosis, MI) patients with and their histopathological data rarely differ; Therefore, early testing for IM caused by EBV is recommended. This article will help physicians face similar cases. [ABSTRACT FROM AUTHOR]

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Key Clinical Message When seeing patients who present with atypical lymphocytes and abdominal pain without accompanying symptoms of pharyngitis or lymphadenopathy, acalculous cholecystitis caused by CMV infection should be considered as a differential diagnosis. Abstract A teenage man presented with a fever and epigastric pain. The patient tested positive for cytomegalovirus IgG and IgM. Abdominal ultrasonography and contrast‐enhanced CT revealed hepatosplenomegaly and gallbladder wall thickening. MRI did not identify gallstones or tumorous lesions. He was diagnosed with infectious mononucleosis and acalculous cholecystitis caused by cytomegalovirus.

ObjectiveThis study aimed to investigate specific clinical diagnostic methods for children with infectious mononucleosis (IM) complicated by acute acalculous cholecystitis (AAC).MethodsWe conducted a retrospective analysis of 171 cases of IM diagnosed in the infectious disease ward of Children's Hospital of Nanjing Medical University between January 2020 and December 2020. All IM patients underwent abdominal ultrasound examinations to assess the liver, gallbladder, and spleen. Fourteen patients with symptoms of AAC underwent a follow-up assessment one week later.ResultsThe estimated incidence of AAC in hospitalized IM children was 8.2%. Both groups of patients presented with fever, abdominal pain, and eyelid edema upon admission. Characteristic radiological findings of AAC were observed, including gallbladder (GB) distention, increased GB wall thickness and increased common bile duct diameter. Analysis of laboratory results revealed no statistically significant differences in leukocyte, absolute lymphocyte count, CD3+, CD3 + CD4+, CD3+ CD8+, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or Gamma-Glutamyl Transferase (GGT) levels between the AAC(+) and AAC(−) groups on admission. However, these parameters were not significant risk factors for AAC. After discharge, relevant indicators in non-AAC patients gradually decreased to normal levels, while those in AAC(+) patients did not show a significant decrease.ConclusionWhile cases of IM complicated by AAC are relatively uncommon, the utilization of abdominal ultrasound offers a reliable tool for confirming this diagnosis. Routine abdominal ultrasound examinations are recommended for IM patients to improve early detection and treatment of associated conditions.

Introduction. Epstein–Barr virus (EBV) is one of the most common herpesviruses and has a pronounced genetic polymorphism. The study of the phylodynamic characteristics of the virus is an important aspect of the study of evolutionary changes in the LMP-1 gene and their consequences. The aim of the work was a philodynamic analysis of EBV isolates from Nizhny Novgorod region based on the C-terminal fragment of the LMP-1 gene. Materials and methods. The study included 158 EBV isolates obtained from blood leukocytes and saliva of children aged 1–17 years with a diagnosis of infectious mononucleosis caused by EBV (n = 68) and apparently healthy children of comparable sex and age (n = 29). LMP-1 genovariants were obtained using the Sanger sequencing method. Comparative analysis of amino acid sequences was performed using the MEGA X program. Philodynamic analysis of the obtained nucleotide sequences and isolates deposited in GenBank was carried out using the BEAST v. 1.10.4 software package. Recombination analysis was performed using the Simplot program. Results. 158 nucleotide sequences of the C-terminal fragment of the LMP-1 gene from Nizhny Novgorod region EBV isolates were obtained and deposited in the GenBank database. The circulation time of the nearest common ancestor for the modified B95-8 genovariants with G212S + E328Q + S366T and NC mutations with the D250N substitution has been established dating back to 1994 and 1923. The rate of evolution of these genovariants was the highest and amounted to 1.298 × 10–4 and 7.868 × 10–4 nucleotide substitutions/site/year. Recombinations were detected in the Nizhny Novgorod region sequences Med-, B95-8, China 1 with mutations G212S, G212S, E214Q, respectively. Conclusion. For the first time, a phylodynamic characterization of Nizhny Novgorod region isolates and LMP-1 EBV genovariants isolated in various regions of the world is given. The data obtained expand the existing understanding of the circulation of EBV LMP-1 genovariants in the territory of the European part of Russia.