Immunization with Components of the Viral Fusion Apparatus Elicits Antibodies That Neutralize Epstein-Barr Virus in B Cells and Epithelial Cells.

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with epithelial-cell cancers and B cell lymphomas. An effective EBV vaccine is not available. We found that antibodies to the EBV glycoprotein gH/gL complex were the principal components in human plasma that neutralized infection of epithelial cells and that antibodies to gH/gL and gp42 contributed to B cell neutralization. Immunization of mice and nonhuman primates with nanoparticle vaccines that displayed components of the viral-fusion machinery EBV gH/gL or gH/gL/gp42 elicited antibodies that potently neutralized both epithelial-cell and B cell infection. Immune serum from nonhuman primates inhibited EBV-glycoprotein-mediated fusion of epithelial cells and B cells and targeted an epitope critical for virus-cell fusion. Therefore, unlike the leading EBV gp350 vaccine candidate, which only protects B cells from infection, these EBV nanoparticle vaccines elicit antibodies that inhibit the virus-fusion apparatus and provide cell-type-independent protection from virus infection.

Comparison of plasma proteomic profiles of patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and infectious mononucleosis.

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.

Risk of multiple sclerosis in individuals with infectious mononucleosis: a national population-based cohort study using hospital records in England, 2003-2023.

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.

Evaluation of novel Epstein-Barr virus-derived antigen formulations for monitoring virus-specific T cells in pediatric patients with infectious mononucleosis.

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.

Siblings reduce multiple sclerosis risk by preventing delayed primary Epstein-Barr virus infection.

Epstein-Barr virus infection, and perhaps almost exclusively delayed Epstein-Barr virus infection, seems to be a prerequisite for the development of multiple sclerosis. Siblings provide protection against infectious mononucleosis by occasionally preventing delayed primary Epstein-Barr virus infection, with its associated high risk of infectious mononucleosis. Each additional sibling provides further protection according to the age difference between the index child and the sibling. The closer the siblings are in age, the higher the protection, with younger siblings being more protective against infectious mononucleosis than older siblings. If the hypothesis that delayed Epstein-Barr virus infection is necessary for the development of multiple sclerosis is true, then the relative risk of multiple sclerosis as a function of sibship constellation should mirror the relative risk of infectious mononucleosis as a function of sibship constellation. Such an indirect hypothesis test is necessitated by the fact that age at primary Epstein-Barr virus infection is unknown for practically all people who have not experienced infectious mononucleosis. In this retrospective cohort study using nationwide registers, we followed all Danes born during the period 1971-2018 (n = 2 576 011) from 1977 to 2018 for hospital contacts with an infectious mononucleosis diagnosis (n = 23 905) or a multiple sclerosis diagnosis (n = 4442), defining two different end points. Relative risks (hazard ratios) of each end point as a function of sibship constellation were obtained from stratified Cox regression analyses. The hazard ratios of interest for infectious mononucleosis and multiple sclerosis could be assumed to be identical (test for homogeneity P = 0.19), implying that having siblings, especially of younger age, may protect a person against multiple sclerosis through early exposure to the Epstein-Barr virus. Maximum protection per sibling was obtained by having a 0-2 years younger sibling, corresponding to a hazard ratio of 0.80, with a 95% confidence interval of 0.76-0.85. The corresponding hazard ratio from having an (0-2 years) older sibling was 0.91 (0.86-0.96). Our results suggest that it may be possible essentially to eradicate multiple sclerosis using an Epstein-Barr virus vaccine administered before the teenage years. Getting there would require both successful replication of our study findings and, if so, elucidation of why early Epstein-Barr virus infection does not usually trigger the immune mechanisms responsible for the association between delayed Epstein-Barr virus infection and multiple sclerosis risk.

Histopathology of peritonitis due to infectious mononucleosis with background Chlamydia trachomatis infection: A case report and literature review.

Epstein-Barr virus (EBV) is a major cause of infectious mononucleosis (IM), characterized by fever, fatigue, sore throat, lymphadenopathy, atypical lymphocytosis, and elevated liver enzymes. However, ascites is a rare complication associated with IM. We present a rare case of IM with ascites and peritonitis in a patient who underwent a peritoneal biopsy. A 20-year-old woman presented with fatigue and abdominal distension. Laboratory examination revealed atypical lymphocytes in peripheral blood (54%) and elevated liver enzymes. EBV serological tests revealed a recent primary infection (EBV VCA IgM 1:160). Computed tomography revealed moderate ascites and peritonitis. Adenocarcinoma was suspected based on the ascites' cytology. Considering possible complications of IM and adenocarcinoma, a laparoscopic biopsy was performed. Histological findings of biopsy specimens from the peritoneum, omentum, and fimbria of the fallopian tube demonstrated severe inflammatory cell infiltration and focal aggregation of large EBV-encoded RNA-1 (EBER1)-positive B cells, mimicking EBV-positive polymorphous B-cell lymphoproliferative disorder. Furthermore, intracytoplasmic inclusion bodies of Chlamydia trachomatis were observed by immunohistochemistry. Real-time polymerase chain reaction detected C. trachomatis in cervical secretions. Two months after laparoscopy, ascites decreased, and the diagnosis was IM-associated peritonitis with C. trachomatis infection. IM should be considered as a differential diagnosis in young patients with ascites.

Infectious mononucleosis due to Epstein-Barr virus reactivation in an immunocompromised 60-year-old patient with COVID-19.

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.

Cytokine Storm Syndromes Associated with Epstein-Barr Virus.

Epstein-Barr virus (EBV) is a ubiquitous and predominantly B cell tropic virus. One of the most common viruses to infect humans, EBV, is best known as the causative agent of infectious mononucleosis (IM). Although most people experience asymptomatic infection, EBV is a potent immune stimulus and as such it elicits robust proliferation and activation of the B-lymphocytes it infects as well as the immune cells that respond to infection. In certain individuals, such as those with inherited or acquired defects affecting the immune system, failure to properly control EBV leads to the accumulation of EBV-infected B cells and EBV-reactive immune cells, which together contribute to the development of often life-threatening cytokine storm syndromes (CSS). Here, we review the normal immune response to EBV and discuss several CSS associated with EBV, such as chronic active EBV infection, hemophagocytic lymphohistiocytosis, and post-transplant lymphoproliferative disorder. Given the critical role for cytokines in driving inflammation and contributing to disease pathogenesis, we also discuss how targeting specific cytokines provides a rational and potentially less toxic treatment for EBV-driven CSS.

Effects of ganciclovir combined with recombinant human interferon-α on clinical efficacy and immune function in children with infectious mononucleosis.

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.

High Epstein-Barr virus capsid antigen IgG level associates with the carriership of CD8+ T cell somatic mutations in the STAT3 SH2 domain.

High carrier prevalence of STAT3 SH2 domain somatic mutations was recently discovered in CD8+ T cells. We found these low-allele-fraction clones in 26% of donors, without difference between multiple sclerosis (MS) patients and controls. Here we tested whether anti-viral antibodies associate with the carriership of these mutant clones. We compared antibody responses against common viruses in mutation carriers vs. non-carriers. Plasma samples of 152 donors (92 MS patients, 60 controls) were analyzed for antibodies against cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6A and parvovirus B19. The mutation carrier status associated with EBV VCA IgG level (p = 0.005) and remained significant after logistic regression (p = 0.036). This association was contributed similarly by MS patients and controls. These results suggest that EBV contributes to the generation or growth of these clones. The pathogenic role of the STAT3 mutant clones in MS is presently unclear, but their detailed characterization warrants further study.

Association between Antibiotic Exposure and the Risk of Rash in Children with Infectious Mononucleosis: a Multicenter, Retrospective Cohort Study.

Present evidence suggests that the administration of antibiotics, particularly aminopenicillins, may increase the risk of rash in children with infectious mononucleosis (IM). This retrospective, multicenter cohort study of children with IM was conducted to explore the association between antibiotic exposure in IM children and the risk of rash. A robust error generalized linear regression was performed to address the potential cluster effect, as well as confounding factors such as age and sex. A total of 767 children (aged from 0 to 18 years) with IM from 14 hospitals in Guizhou Province were included in the final analysis. The regression analysis implied that exposure to antibiotics was associated with a significantly increased incidence of overall rash in IM children (adjusted odds ratio [AOR], 1.47; 95% confidence interval [CI], ~1.04 to 2.08; P = 0.029). Of 92 overall rash cases, 43 were probably related to antibiotic exposure: two cases (4.08%) in the amoxicillin-treated group and 41 (8.15%) in the group treated with other antibiotics. Regression analysis indicated that the risk of rash induced by amoxicillin in IM children was similar to that induced by other penicillins (AOR, 1.12; 95% CI, ~0.13 to 9.67), cephalosporins (AOR, 2.45; 95% CI, ~0.43 to 14.02), or macrolides (AOR, 0.91; 95% CI, ~0.15 to 5.43). Antibiotic exposure may be associated with an increased risk of overall rash in IM children, but amoxicillin was not found to be associated with any increased risk of rash during IM compared to other antibiotics. We suggest that clinicians be vigilant against the occurrence of rash in IM children receiving antibiotic therapy, rather than indiscriminately avoiding prescribing amoxicillin.

Bilateral upper eyelid swelling (Hoagland sign) in Epstein-Barr infectious mononucleosis: prospective experience.

BACKGROUND: The typical presentation of Epstein-Barr virus infectious mononucleosis includes fever, pharyngitis, measles-like rash, jaundice, and enlarged lymph nodes, liver, or spleen. A painless bilateral swelling of the upper eyelid, sometimes with drooping of the lateral aspect, may also occur. This sign, referred to as Hoagland sign, is not or only marginally mentioned in reviews and textbooks. METHODS: Between 2019 and 2021, two of us evaluated all subjects with a positive acute Epstein-Barr virus serology for the typical signs of mononucleosis and for the possible existence of the Hoagland sign. RESULTS: During the mentioned period, the diagnosis of mononucleosis was made in 26 (14 females and 12 males) subjects aged from 9.0 to 33 years. The initial presentation included fever in 24, enlarged cervical lymph nodes in 23, pharyngitis in 21, a palpable liver in 7, a palpable spleen in 7, jaundice in 2, and a measles-like rash in 2 cases. The Hoagland sign was noted in 14 cases. Patients with and without Hoagland sign did not significantly differ with respect to age and sex. CONCLUSIONS: The Hoagland sign is an easily identifiable clinical sign that is common and likely helpful early in the course of Epstein-Barr virus infectious mononucleosis. There is a need to expand awareness of this sign among physicians.

Comparative study of biomarkers for the early identification of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in infectious mononucleosis.

BACKGROUND AND AIM: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early. METHODS: We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them. RESULTS: Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 µg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%. CONCLUSIONS: IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations.

An update on Epstein-Barr virus-and human T-lymphotropic virus type-1-induced cutaneous manifestations. CME Part II.

The Epstein-Barr virus (EBV) is a DNA virus that infects 90% of the human population, is responsible for certain cutaneous lymphomas (extranodal NK/T-cell lymhoma, hydroa vacciniforme lymphoproliferative disorder, lymphomatoid granulomatosis, others), and can be associated with a variety of cutaneous manifestations (eg, infectious mononucleosis, severe mosquito bite allergy, chronic active EBV disease, Gianotti-Crosti syndrome). EBV-related skin disorders are frequent in certain populations (South and Cental America, Africa, Asia, and Oceania) and can be diagnostically challenging. The human T-lymphotropic virus type-1 is a retrovirus, which is known to be associated with adult T-cell leukemia/lymphoma, neurologic disorders, but also cutaneous non-neoplastic manifestations (infective dermatitis, infections, and infestations). We performed an updated revision of the clinical dermatologic and histopathologic findings associated with the cutaneous non-neoplastic and preneoplastic disorders occurring in association with the EBV and human T-lymphotropic virus type-1.

Diagnosis of Epstein-Barr and cytomegalovirus infections using decision trees: an effective way to avoid antibiotic overuse in paediatric tonsillopharyngitis.

BACKGROUND: The incidence of tonsillopharyngitis is especially prevalent in children. Despite the fact that viruses cause the majority of infections, antibiotics are frequently used as a treatment, contrary to international guidelines. This is not only an inappropriate method of treatment for viral infections, but it also significantly contributes to the emergence of antibiotic-resistant strains. In this study, EBV and CMV-related tonsillopharyngitis were distinguished from other pathogens by using machine learning techniques to construct a classification tree based on clinical characteristics. MATERIALS AND METHODS: In 2016 and 2017, we assessed information regarding 242 children with tonsillopharyngitis. Patients were categorized according to whether acute cytomegalovirus or Epstein-Barr virus infections were confirmed (n = 91) or not (n = 151). Based on symptoms and blood test parameters, we constructed decision trees to discriminate the two groups. The classification efficiency of the model was characterized by its sensitivity, specificity, positive predictive value, and negative predictive value. Fisher's exact and Welch's tests were used to perform univariable statistical analyses. RESULTS: The best decision tree distinguished EBV/CMV infection from non-EBV/CMV group with 83.33% positive predictive value, 88.90% sensitivity and 90.30% specificity. GPT (U/l) was found to be the most discriminatory variable (p < 0.0001). Using the model, unnecessary antibiotic treatment could be reduced by 66.66% (p = 0.0002). DISCUSSION: Our classification model can be used as a diagnostic decision support tool to distinguish EBC/CMV infection from non EBV/CMV tonsillopharyngitis, thereby significantly reducing the overuse of antibiotics. It is hoped that the model may become a tool worth considering in routine clinical practice and may be developed to differentiate between viral and bacterial infections.

Risk factors for persistent fever in children with infectious mononucleosis.

BACKGROUND: Fever is a common symptom in children with infectious mononucleosis (IM). However, the significance of the duration of a fever is poorly understood. This study aimed to analyze the risk factors for persistent fever in children with IM. METHODS: Patients diagnosed with IM (aged <18 years; except those with concomitant hematological malignancies or tumor diseases) in a high-volume academic hospital in 2019 were reviewed from a prospectively maintained database. Children with transient fever (≤7 days) were compared with those with persistent fever (>7 days). The risk factors for persistent fever in children with IM were examined using binary logistic regression. Furthermore, the predictive ability of these risk factors was assessed and presented using a receiver operating characteristic (ROC) curve. RESULTS: Of the 184 children included in this study, 131 (71.96%) belonged to the transient fever group and 53 (28.04%) belonged to the persistent fever group (median age: 49 and 64 months, respectively; p = 0.093). Statistical significance was observed in hepatomegaly, alanine aminotransferase level, blood triglyceride level, and blood Epstein-Barr virus polymerase chain reaction (EBV-PCR) copy number (all p < 0.05). Binary logistic regression revealed that high blood triglyceride level was the risk factor for persistent fever in children with IM. High blood triglyceride level predicted persistent fever duration with an area under the ROC curve of 0.73 and an optimal cutoff value of 1.315 mmol/L. CONCLUSION: High blood triglyceride level was the risk factor for persistent fever in children with IM. Thus, children with elevated levels of blood triglycerides need additional care. To diagnose IM, a blood EBV-PCR is more useful than a throat-swab EBV-PCR.

Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers.

Since the early 1980s, Epstein-Barr virus (EBV) infection has been described as one of the main risk factors for developing multiple sclerosis (MS), and recently, new epidemiological evidence has reinforced this premise. EBV seroconversion precedes almost 99% of the new cases of MS and likely predates the first clinical symptoms. The molecular mechanisms of this association are complex and may involve different immunological routes, perhaps all running in parallel (i.e., molecular mimicry, the bystander damage theory, abnormal cytokine networks, and coinfection of EBV with retroviruses, among others). However, despite the large amount of evidence available on these topics, the ultimate role of EBV in the pathogenesis of MS is not fully understood. For instance, it is unclear why after EBV infection some individuals develop MS while others evolve to lymphoproliferative disorders or systemic autoimmune diseases. In this regard, recent studies suggest that the virus may exert epigenetic control over MS susceptibility genes by means of specific virulence factors. Such genetic manipulation has been described in virally-infected memory B cells from patients with MS and are thought to be the main source of autoreactive immune responses. Yet, the role of EBV infection in the natural history of MS and in the initiation of neurodegeneration is even less clear. In this narrative review, we will discuss the available evidence on these topics and the possibility of harnessing such immunological alterations to uncover predictive biomarkers for the onset of MS and perhaps facilitate prognostication of the clinical course.

INFECTIOUS MONONUCLEOSIS DURING THE WAR AND COVID INFECTION PANDEMIC IN UKRAINE.

OBJECTIVE: The aim: To analyze the current views on diagnosis and management of infectious mononucleosis in children. The purpose of our work is also a comparative characteristic of the incidence of infectious mononucleosis in Ukraine and the city of Poltava (2006-2022). PATIENTS AND METHODS: Materials and methods: The data of scientific literature have been analyzed, using the bibliosemantic method of study. We used a retrospective analysis of statistical data on the incidence of infectious mononucleosis 2006-2022 and the most frequent cases of infectious pathology in children in the period 2019- 2022, and also conducted an analysis of the percentage of those vaccinated according to the vaccination calendar. RESULTS: Results: We had an increase in the incidence in 2009, but in subsequent years it was in the range of 23-25.2 per 100.000 children. The incidence of patients diagnosed with infectious mononucleosis per 100.000 of the children population in the Poltava region is one of the lowest in Ukraine, accounting for 8.1 - 10.1% over the past 3 years, which can be explained by the decrease in visits by parents and their children to the hospital to avoid contact with patients with the coronavirus disease and the fact that our region also had rather lower rates of children with Covid-19 compared in Ukraine. CONCLUSION: Conclusions: the situation with the spread of infectious mononucleosis in children in Ukraine is such that it causes concern, and when comparing the incidence in 2009 and 2022, the authors noted an increase in the overall incidence of this nosology by 5%.

Analysis of two laboratory tests for determination of EBV-IM in children.

This study aimed to explore the application value of two laboratory tests in the diagnosis of Epstein-Barr virus-associated infectious mononucleosis (EBV-IM) in children. From January 2018 to December 2020, 166 patients with EBV-IM were included in this study. Two methods were used in the analysis. The results of both tests were compared and analyzed. The age of onset of EBV-IM is mainly distributed in the range of 0-6 years, and no difference by gender is observed. The sensitivity and specificity of EBV testing by PCR were 49.4% and 89.8%, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.714 (0.662-0.762). When using the immunofluorescence method to detect EBV antibodies, the two indices with the highest diagnostic efficacy were low-affinity EBV-CA IgG and EBV-CA IgM, and their AUC values were 0.798 (0.751-0.840) and 0.663 (0.609-0.713), respectively. When combining the two indices for testing, the AUC values of EBV-CA IgM + low-affinity EBV-CA IgG, EBV-DNA+EBV-CA IgM, and EBV-DNA+low-affinity EBV-CA IgG were 0.904 (0.867-0.933), 0.768 (0.719-0.812), and 0.963 (0.937-0.981), respectively. The diagnostic efficacy of the combined EBV-DNA+EBV-CA IgM + low-affinity EBV-CA IgG test was optimal compared with that of a single index or the combination of two indices, with an AUC of 0.999 (0.986-1.000; p < 0.05), sensitivity of 100%, and specificity of 89.8%. The combined immunofluorescence and real-time PCR methods have high sensitivity and specificity and good application value in the clinical diagnosis of EBV-IM.

Adenosine deaminase as a marker for the severity of infectious mononucleosis secondary to EBV in children.

BACKGROUND: Infectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed to determine whether adenosine deaminase is a marker of severity in children with infectious mononucleosis, especially those with elevated alanine transaminase levels. METHODS: This case-control study was conducted at the Children's Hospital of Soochow University. A total of 104 children with infectious mononucleosis and 50 controls with other acute infections and fever, tonsillitis, or lymphadenitis, were enrolled in the study. Among the 104 children with infectious mononucleosis, 54 had normal alanine transaminase levels and 50 had elevated alanine transaminase levels. The children's clinical and laboratory data were analyzed to assess the diagnostic value of adenosine deaminase in the three groups. RESULTS: The adenosine deaminase level in the infectious mononucleosis group was significantly higher than that in the control group (P < 0.001). The adenosine deaminase levels were highly correlated with lymphocyte count, CD3+CD8+ T cells (%), CD4+/CD8+ ratio, and CD3-CD19+ (%) (r > 0.7, P < 0.01). The sensitivity and specificity of adenosine deaminase in predicting children with infectious mononucleosis were 97.1% and 94.0%, respectively. Furthermore, multivariate regression analysis revealed that adenosine deaminase level was a risk factor for elevated alanine transaminase in children with infectious mononucleosis. CONCLUSIONS: Adenosine deaminase may be a marker of the severity of infectious mononucleosis in children, and a predictor of elevated alanine transaminase in children with infectious mononucleosis.