This study aimed To describe the 10-year temporal trends of serum Epstein-Barr virus (EBV) DNA positivity among pediatric patients tested at Hangzhou Children's Hospital, and to explore demographic and seasonal variations across pre-pandemic, pandemic, and post-pandemic periods. A total of 11,689 serum samples from children aged 0-15 years who underwent EBV nucleic acid testing at Hangzhou Children's Hospital from January 2016 to December 2025 were retrospectively analyzed, including 2,160 positive results. Demographic characteristics (sex, age), visit type (outpatient/inpatient), and temporal distributions (year, month) were examined. Monthly detection rates were calculated using monthly testing denominators. Group comparisons were performed using chi-square tests; the linear-by-linear association Chi-square test was applied to annual rates. Multivariable negative-binomial regression with offset for monthly test volumes and interrupted time-series analysis (ITSA) were used to evaluate independent associations with secular trend, seasonality, and pandemic phase. The overall EBV-DNA detection rate was 18.48% (2,160/11,689) among tested samples. A deduplication sensitivity analysis yielded a corrected patient-level rate of 18.26%, confirming robustness. Females (20.04%) had a higher rate than males (17.26%, χ[2] = 14.66, p < 0.01). Outpatients (28.24%) showed a higher rate than inpatients (16.62%, χ[2] = 141.6, p < 0.01). Age distribution was concentrated in children aged 1-8 years (86.02% of positives), peaking at 5 years (25.14%) and lowest in infants < 1 year (2.46%). Annual detection rates rose from 7.25% (2016) to 29.69% (2025) (linear-by-linear association Chi-square test, p < 0.01). Monthly detection rates suggested a descriptive bimodal pattern, with an autumn peak (September-November, 21.07%) and a spring peak (March-May, 17.88%), although formal testing did not reach statistical significance (joint Wald χ[2] = 14.72, df = 11, p = 0.195). Across pandemic phases, unadjusted rates were 12.03% (pre-pandemic), 19.61% (pandemic), and 21.64% (post-pandemic). Multivariable negative-binomial regression revealed that the long-term secular trend was the only significant predictor (adjusted rate ratio [aRR] = 1.029 per month, 95% CI: 1.000-1.059, p = 0.047), while pandemic phase (aRR = 1.171, p = 0.347) and post-pandemic phase (aRR = 1.233, p = 0.288) were not significant. ITSA showed no significant level or slope changes at either breakpoint (all p > 0.05). In this hospital-based tested population, serum EBV-DNA positivity showed a significant upward secular trend over 2016-2025. The post-pandemic increase was primarily driven by a pre-existing secular trend rather than a discrete "rebound" attributable to immunity debt. Due to selection bias from non-standardized testing indications, these findings should not be generalized to the general pediatric community. Future studies with population-based sampling and serological differentiation of primary infection versus reactivation are needed.

The pediatric gastric mucosa harbors a diverse bacterial and viral community, and its relationship to gastric inflammation remains incompletely understood. We characterized bacterial and viral detection in gastric biopsies from 193 children undergoing endoscopy for chronic abdominal pain, analyzing 507 samples from the antrum, corpus, and incisura angularis. Molecular detection revealed frequent herpesvirus presence, with HHV6 and HHV7 predominating, while Epstein-Barr virus (EBV) was detected in a smaller but consistent subset. HHV6/HHV7 also showed non-uniform anatomical distribution across gastric regions. Multivariable analyses identified Helicobacter pylori (H. pylori) as the microorganism most strongly associated with moderate-to-severe chronic inflammation. EBV DNA detection also showed a positive association with inflammation, including in H. pylori-negative patients. Zoonotic non-H. pylori Helicobacter (NHPH) species were commonly detected but did not show consistent population-level associations with inflammation. Overall, these findings support the presence of a heterogeneous gastric microbial landscape in children. Within this landscape, H. pylori remained the microorganism most strongly associated with gastric inflammation, whereas EBV showed the most consistent pattern of association among the remaining microorganisms. These observations generate hypotheses regarding potential interactions among gastric microorganisms that should be addressed in longitudinal and mechanistic studies.

Epstein-Barr virus (EBV) infection is ubiquitous, affecting over 90% of the global population, and while typically benign, it can rarely cause acute liver failure - a life-threatening complication that is frequently fatal. This review comprehensively reviews two overlapping clinical and pathogenetic patterns of EBV-associated hepatic failure - isolated severe EBV hepatitis and EBV-triggered hemophagocytic lymphohistiocytosis (HLH) - which are best understood as ends of a clinical spectrum rather than discrete entities. In isolated EBV hepatitis, liver injury is driven by CD8-positive T cells attacking EBV-infected B cells, causing bystander hepatocyte necrosis; inflammation remains confined to the liver, and supportive care is usually sufficient. By contrast, EBV-HLH involves EBV-infected monoclonal T or natural killer cells triggering a systemic cytokine storm (including interferon-gamma, tumor necrosis factor-alpha, interleukin-6, and interleukin-18) with hemophagocytosis, requiring immediate immunosuppression. In one pediatric cohort, an EBV DNA load exceeding 100,000 copies per milliliter was associated with a more than ten-fold increase in mortality, although no universally validated cutoff has been established across age groups or sample types; T-cell EBV DNA load provides additional prognostic information. Blood purification is an experimental adjunctive strategy in refractory cases, supported by very low-certainty evidence. We also discuss risk factors, diagnostic algorithms (including EBV DNA load, HLH-2004 criteria, and histopathology), therapeutic strategies (supportive care, antiviral therapy, immunomodulation, and liver transplantation), and future research priorities. Early recognition of HLH is life-saving. This review provides a practical clinical framework for differentiating these two entities and highlights knowledge gaps for future investigation.

Sequence-selective control of gene expression by synthetic DNA-binding molecules is attractive for developing chemical biology tools and potential therapeutic applications. Here we report a cyclic pyrrole/lysine polyamide (cPKP) that preferentially binds AT-rich DNA, with selective recognition of ATAT and ATGT motifs. In a HeLa nuclear extract-based transcription system, cPKP repressed transcription in a promoter-dependent manner, showing stronger inhibition of a cytomegalovirus (CMV) core promoter than of the human c-MYC promoter. RNA sequencing showed that cPKP was associated with downregulation of genes whose proximal promoters were enriched for ATAT and ATGT motifs, while causing limited perturbation of global cellular homeostasis in HeLa cells. Together, these results establish cPKP as a motif-selective DNA-binding scaffold that can modulate transcription in a promoter-dependent manner with limited global transcriptomic perturbation in human cells.

Human herpesviruses (HHV) remain latent after primary infection and may reactivate during critical illness. HHV reactivation has been associated with adverse clinical outcomes, yet its pathogenic significance and optimal management remain unclear. This review summarizes the dysregulated immune mechanisms and risk factors for HHV reactivation in critical illness, treatment options, outcomes, current diagnostic challenges, and emerging precision medicine approaches. Critical illness induces profound immune dysregulation characterized by an initial hyperinflammatory response followed by immunosuppression, T-cell exhaustion, impaired natural killer cell function, and disrupted antiviral surveillance. These changes facilitate reactivation of latent HHV, including herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6). HSV and CMV reactivation in mechanically ventilated and septic patients have been associated with prolonged mechanical ventilation, longer intensive care unit (ICU) stay, secondary infections, and increased mortality. However, the distinction between clinically significant disease from asymptomatic reactivation remains challenging. Current evidence does not support routine antiviral prophylaxis in immunocompetent ICU patients. Emerging approaches including metagenomic next-generation sequencing, host transcriptomics, immune phenotyping, and multi-omics integration may improve risk stratification and identify patient subgroups that are most likely to benefit from targeted intervention. HHV reactivation may serve as a biomarker and potential mediator of adverse outcomes. Improved understanding of host-virus interactions, coupled with precision medicine that integrates virological and immunological data, is required to differentiate clinically relevant reactivation from epiphenomena and to guide individualized therapeutic strategies.

BackgroundGuillain-Barré syndrome (GBS) can be difficult to recognise in advanced untreated HIV, particularly where cerebrospinal fluid analysis and electrophysiology are unavailable.MethodsWe retrospectively reviewed adults with advanced HIV who were not receiving antiretroviral therapy and presented with acute symmetrical weakness at an Indian HIV specialty centre during 2019-2020. Cases were classified as clinically probable GBS with Brighton Collaboration level 3 diagnostic certainty.ResultsEight cases were identified among 139 admissions (5.8%). Mean CD4 count 78 cells/mm[3]. All eight had multiple concurrent infectious conditions. Herpesvirus-associated syndromes included ulcerative oesophagitis compatible with a herpesvirus-associated process (n=5), antecedent herpes zoster (n=2), or diarrhoeal illness with supportive CMV IgG serology (n=1). Seven recovered after multimodal treatment; one died.ConclusionsThis repeated clinical pattern of coexistence is hypothesis-generating but does not establish active viral reactivation, directionality, or causality. Pragmatic syndromic recognition and treatment remain necessary when definitive diagnostics are unavailable.

Background and objectives Varicella-zoster (VZV) virus infection can be severe in children with nephrotic syndrome. Lack of varicella vaccination through the national immunisation programme in India leaves many vulnerable to infection. We conducted this study to document the seroprevalence of Varicella antibodies in patients with nephrotic syndrome. Methods This cross-sectional study (Oct 2024-May 2025) was conducted at a tertiary-care teaching hospital in India, in children (1-18 y) with nephrotic syndrome (both steroid-sensitive and steroid-resistant) in disease remission. Serum VZV IgG antibodies were measured using the EUROIMMUN ELISA kit; titres ≥100 IU/L were considered seroprotective. Results 100 patients were enrolled (median age 8 y). None had received varicella vaccination, and only two reported prior infection. Overall seroprotection was 22% with a geometric mean titre of 9.472 IU/L [median (IQR) 7.59 (3.35; 73.38) IU/L]. No significant difference was observed in titres between steroid-sensitive and steroid-resistant nephrotic syndrome (P=0.532), but seroprotection increased with age (11.1% in <5 y to 33.3% in >10 y). Interpretation and conclusions Low seroprevalence likely reflects the inadequacy of natural immunity and absence of routine varicella vaccination, warranting larger seroprevalence studies and future research on the need for priority immunisation for this high-risk population.

Objective: To investigate the impact of collateral cytomegalovirus (CMV) -positive versus CMV-negative donors on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Method: This retrospective cohort study analyzed CMV-related events and survival outcomes in allo-HSCT recipients with CMV seropositive who received grafts from CMV-negative (CMV-negative donor group) or collateral CMV-positive (collateral CMV-positive donor group) haploidentical donors at Peking University People's Hospital from January 2017 to March 2025. Results: A total of 126 patients were enrolled, including 16 CMV-negative and 58 collateral CMV-positive donors before the availability of letermovir, and 27 CMV-negative and 25 collateral CMV-positive donors after the availability of letermovir. With a median follow-up of 1 091 (660, 1 536) days, before the availability of letermovir in China, the CMV-negative donor group had a significantly higher incidence of refractory CMV viremia (87.5% vs 50.0%, P=0.007) and a longer median duration of first CMV viremia [29 (95% CI: 25-33) vs 17 (95% CI: 15-19) days, P=0.004] than the collateral CMV-positive donor group. The use of letermovir significantly delayed the onset of first post-transplant CMV viremia in both groups: from day 37 (95% CI: 31-43) to day 140 (95%CI: 136-144) in the CMV-negative donor group (P<0.001) and from day 36 (95% CI: 33-39) to day 111 (95% CI: 76-146) in the collateral CMV-positive donor group (P=0.013). With letermovir prophylaxis, the difference in the median duration of the first CMV viremia between the CMV-negative and collateral CMV-positive donor groups was no longer significant [18 (95% CI: 17-19) vs 12 (95%CI: 0-25) days, P=0.313]. Letermovir reduced the incidence of refractory CMV viremia in the CMV-negative donor group (40.7% vs 87.5%, P=0.003), but the incidence remained higher than that in the collateral CMV-positive donor group (40.7% vs 12.0%, P=0.020). Regardless of letermovir use, there were no statistically significant differences in the 3-year overall survival, non-relapse mortality, or cumulative relapse rate between the CMV-negative and collateral CMV-positive donor groups (all P>0.05). Multivariate analysis showed that CMV disease was an independent risk factor for overall survival (HR=3.0, 95%CI: 1.3-7.3, P=0.014) and non-relapse mortality (HR=3.1, 95%CI: 1.1-8.8, P=0.035). Refractory CMV viremia was an independent risk factor for CMV disease (HR=12.0, 95%CI: 2.9-50.7, P=0.001). Logistic regression analysis showed that having a CMV-negative donor status without letermovir prophylaxis was an independent risk factor for refractory CMV viremia (P=0.005) . Conclusion: CMV-negative donors increase the risk of CMV-related events in recipients. Although letermovir prophylaxis mitigates this risk, the incidence of refractory CMV viremia remains higher in the CMV-negative donor group than in the collateral CMV-positive donor group, whereas the overall survival outcomes are comparable between the two donor sources.

Varicella zoster virus (VZV) reactivation with central nervous system (CNS) involvement is an uncommon but important cause of lymphocytic meningitis in both immunocompromised and immunocompetent individuals. While cranial presentations, especially V1 involvement, are well documented, spinal-dermatomal VZV meningitis is rarely reported. We conducted a systematic review of PubMed, Scopus, and Embase using PRISMA guidelines to identify all cases of laboratory-confirmed VZV meningitis or encephalitis with a dermatomal rash in immunocompetent adults affecting spinal levels C1 and below. Data extracted included demographics, dermatome distribution, CSF findings, treatment, and outcomes. We also report a novel case from our institution involving isolated C4-C5 involvement. Seventeen total cases met inclusion, including our 44-year-old male patient who presented with fever, severe headache, and a right-sided vesicular rash in the C4-C5 dermatomes. He was initially misdiagnosed with a tick-borne illness. Mean CSF values across all cases were WBC count 382/µL (SD ± 270), protein 177 mg/dL (SD ± 106), and glucose 52.7 mg/dL (SD ± 15.8). IV acyclovir was used in 15 of 17 cases, with oral acyclovir (41%) or valacyclovir (29%) as the most common step-down therapies. Mean treatment duration was 14 days, and average length of hospital stay was 6.4 days. All patients survived and made a full recovery. Spinal-dermatomal VZV meningitis can occur in immunocompetent adults, including cases with cervical involvement. Early recognition of the rash pattern and timely PCR testing are essential for accurate diagnosis and prompt antiviral therapy, which is associated with favorable outcomes.

Malignant catarrhal fever (MCF) is a severe lymphoproliferative disease of domestic and wild ruminants caused by macaviruses, mainly ovine gammaherpesvirus 2 (OvHV-2) and alcelaphine gammaherpesvirus 1 (AlHV-1). Although relevant in sub-Saharan Africa, molecular epidemiological data remain limited, particularly in Namibia. This study investigated the occurrence and diversity of MCF viruses in Namibian livestock and contextualised local strains globally.Fifteen samples from cattle and sheep suspected of MCF were collected across five Namibian regions in 2023. Viral DNA was screened by duplex nested PCR, followed by amplification and sequencing of selected OvHV-2 (ORF50, ORF75, Ov9.5) and AlHV-1 (ORF50, A9.5) genomic regions. Phylogenetic and genetic distance analyses assessed viral diversity.OvHV-2 was the most commonly reported, being detected in 13/15 samples from both symptomatic cattle and asymptomatic sheep, whereas AlHV-1 was identified in two bovine cases. OvHV-2 sequences showed limited diversity and clustered into two main clades, without clear geographic structuring and with intermixing between host species. Several Namibian strains were closely related to sequences from Africa, Europe, Asia, and North America, depending on the genomic region analysed. AlHV-1 sequences were related to strains from southern and eastern Africa.These findings support widespread OvHV-2 circulation and indicate sheep as a likely infection source for cattle. The lack of spatial structure and presence of multiple clades suggest complex transmission dynamics, potentially influenced by animal movements, although the role of livestock trade and wildlife-mediated transmission remains unclear. Enhanced molecular surveillance, biosecurity, and control of animal translocations are needed to mitigate MCF impact in the region.