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BACKGROUND: This study characterizes the clinical utility and validity of the Karius test (KT), a plasma microbial cell-free DNA sequencing platform, as an infection surveillance tool among hematopoietic stem cell transplant (HCT) recipients, including monitoring for cytomegalovirus (CMV) and detecting infections relative to standard microbiologic testing (SMT). METHODS: A prospective, observational cohort study was performed among adult HCT recipients as inpatients and outpatients. Serial KTs were performed starting with 1 sample within 14 days before HCT, then weekly from 7-63 days posttransplant then monthly from 3-12 months post-HCT. Diagnostic performance of KT versus CMV polymerase chain reaction was evaluated with positive percent agreement and negative percent agreement. Infectious events (

Cytomegalovirus colitis should be considered in a patient presenting with bloody stool even among immunocompetent patients.

The compartmentalization of eukaryotic cells presents considerable challenges to the herpesvirus life cycle. The herpesvirus tegument, a bulky proteinaceous aggregate sandwiched between herpesviruses' capsid and envelope, is uniquely evolved to address these challenges, yet tegument structure and organization remain poorly characterized. We use deep-learning-enhanced cryogenic electron microscopy to investigate the tegument of human cytomegalovirus virions and noninfectious enveloped particles (NIEPs; a genome packaging-aborted state), revealing a portal-biased tegumentation scheme. We resolve atomic structures of portal vertex-associated tegument (PVAT) and identify multiple configurations of PVAT arising from layered reorganization of pUL77, pUL48 (large tegument protein), and pUL47 (inner tegument protein) assemblies. Analyses show that pUL77 seals the last-packaged viral genome end through electrostatic interactions, pUL77 and pUL48 harbor a head-linker-capsid-binding motif conducive to PVAT reconfiguration, and pUL47/48 dimers form 45-nm-long filaments extending from the portal vertex. These results provide a structural framework for understanding how herpesvirus tegument facilitates and evolves during processes spanning viral genome packaging to delivery.

INTRODUCTION: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. CASE PRESENTATION: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous hemorrhage and ultimately underwent right eye enucleation. Interestingly, histopathological analysis of the enucleated eye revealed concomitant CMV retinitis alongside retinoblastoma. After consultation with infectious disease, antiviral treatment was not initiated as the patient remained asymptomatic and maintained a recovered immune system. Repeat CMV PCR confirmed viral clearance. The patient received a prosthetic eye and continues to be monitored for retinoblastoma recurrence. CONCLUSION: Clinicians should be aware of the potential for CMV retinitis to develop in retinoblastoma patients receiving chemotherapy, which may complicate clinical decision-making and management. Timely identification of CMV retinitis in this setting may improve patient ocular outcomes and overall prognosis.

Primary infection or reactivation of latent human cytomegalovirus (HCMV) or herpes simplex viruses (HSV) 1 or 2 during pregnancy can transmit the virus in utero or during natural childbirth to the fetus. The majority of these infections are asymptomatic at birth but may present later with potentially lethal disseminated infection or meningitis (HSV), or long-term neurodevelopmental sequelae including sensorineural hearing loss or neurodevelopmental impairments (HCMV). Unfortunately, early signs and symptoms of disseminated viral infections may be misdiagnosed as bacterial sepsis. Therefore, immediate testing for viral etiologies may not be ordered or even considered by skilled clinicians. In asymptomatic HCMV infections, early detection is necessary to monitor for and treat future neurologic sequelae. In acutely ill-appearing infants, specific detection of viruses against other disease-causing agents is vital to inform correct patient management, including early administration of the correct antimicrobial(s). An ideal test should be rapid, inexpensive, require low sample volumes, and demonstrate efficacy in multiple tissue matrices to aid in timely clinical decision-making for neonatal infections. This work discusses the development of a rapid probe-free qPCR assay for HSV and HCMV that enables early and specific detection of these viruses in neonates. The assays probe free chemistry would allow easier extension to a broad-based multiplexed pathogenic panel as compared to assays utilizing sequence-specific probes or nested PCR.

Background: The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy. Case presentation: A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed. Conclusion: Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies. [ABSTRACT FROM AUTHOR]

Introduction: Intrauterine transfusion is the treatment for fetal anemia resulting from maternal alloimmunization, infections (parvovirus B19 and cytomegalovirus), single demise of a monochorionic twin, chorioangioma, and other rare conditions. Fetal analgesia is mandatory to reduce movement and pain perception during the procedure. This study aims to evaluate perinatal outcomes for such procedures, following the routine use of fetal analgesia in our clinical practice. Materials and methods: Retrospective analysis of cases from 2009 to 2022, including all confirmed fetal anemia with fetal blood sampling. After fetal analgesia, Rh-negative concentrated red blood cells were transfused, with ultrasonographic follow-up 24 h and 1 week later. In case of suspected brain lesion, magnetic resonance imaging was performed. Elective delivery was considered in case of persistent anemia after 34 weeks. Post-natal follow-up and comprehensive obstetric and perinatal outcomes data were collected. Results: Altogether 59 anemic fetuses were included, with 34 (57.6%) being hydropic. The causes of anemia were maternal alloimmunization (22, 37.3%), infections (13, 22%), monochorionicity (10, 16.9%), rare conditions (9, 15.3%), and two chorioangiomas (3.4%). The median gestational age at the procedure was 25.2 weeks (18-32 weeks), with no related preterm premature rupture of membranes (<48 h), or side effects from fetal analgesia. Gestational age at delivery was 33weeks (26-41 weeks), with survival rate of 90%. There were four fetal demises, two termination of pregnancies, and eight neonatal deaths due to persistent severe anemia after preterm delivery. The main contributors to adverse outcome were the type of anemia, and the management with a preterm delivery. Conclusion: Intrauterine transfusion of red blood cells under analgesia is safe, with low incidence of obstetric complication. [ABSTRACT FROM AUTHOR]

Background: Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. Methods: Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). Results: Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. Conclusion: CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Bone marrow transplantation (BMT) saves lives in Omenn syndrome, a severe immunodeficiency disorder. Timely genetic diagnosis and matched donor BMT are crucial. Emphasis on newborn screening and multidisciplinary care improves outcomes for infants with inherited disorders. Prompt intervention and comprehensive management are vital for a successful transplant outcome. Omenn syndrome represents a severe variant of combined immunodeficiency characterized by disregulated immune responses and susceptibility to recurrent infections. We present the case of a 3‐month‐old female infant initially presenting with upper respiratory infection symptoms and a diffuse rash, unresponsive to local treatment. At 4 months of age, the patient underwent allogeneic bone marrow transplantation (BMT) utilizing stem cells from a fully matched sibling donor. Pre‐transplant conditioning included antimicrobial prophylaxis and supportive therapies. Following BMT, the patient received immunosuppressive medications to prevent graft rejection and graft‐versus‐host disease. Clinical monitoring post‐transplant showed timely neutrophil and platelet engraftment, with subsequent follow‐up demonstrating stable clinical parameters and negative cytomegalovirus status. The case highlights the importance of timely diagnosis and treatment in managing severe immunodeficiency disorders, demonstrating the potential for successful outcomes with appropriate timely interventions. Regular monitoring and follow‐up appointments were crucial in ensuring the success of the treatment. This case also emphasizes the significance of multidisciplinary care and genetic testing in identifying and managing rare immunodeficiency disorders. The successful outcome in this case provides hope for improved treatment options and better patient outcomes in the future. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) infection is a major cause of transplantation‐related morbidity and mortality. This study assessed the utility of the QuantiFERON monitor (QFM; Qiagen) for the prediction of early CMV infection and viral burden. Methods: QuantiFERON‐CMV (QF‐CMV; Qiagen) and QFM were measured at the post‐allogeneic hematopoietic stem cell transplantation (HSCT) week 4. CMV DNA was measured at every visit until post‐HSCT week 24. The QFM cutoff specific to CMV infection was established. Result: At the post‐HSCT week 4, the QFM cutoff predicting CMV infection was 86.95 IU/mL. While QF‐CMV results at the post‐HSCT week 4 were associated with high‐level CMV infection (CMV DNA ≥ 5,000 IU/mL) but not with CMV infection (CMV DNA ≥ 500 IU/mL), QFM was associated with both CMV infection and high‐level CMV infection. Both indeterminate QF‐CMV and nonreactive QFM were associated with increased peak CMV DNA. Conclusion: Low QFM is a risk factor for CMV infection and increased CMV viral loads. QFM at post‐HSCT week 4 can be utilized as an assay to predict the risk and burden of early CMV infection in HSCT recipients, in conjunction with other risk factors. [ABSTRACT FROM AUTHOR]

Background: Reactivation of viral infections, in particular cytomegalovirus (CMV) and adenovirus (ADV), cause morbidity and non‐relapse‐mortality in states of immune deficiency, especially after allogeneic hematopoietic cell transplantation (allo‐HCT). Against the background of few available pharmacologic antiviral agents, limited by toxicities and resistance, adoptive transfer of virus‐specific T‐cells (VST) is a promising therapeutic approach. Methods: We conducted a single‐center retrospective analysis of adult patients treated with ADV‐ or CMV‐specific T‐cells in 2012–2022. Information was retrieved by review of electronic health records. Primary outcome was a response to VST by decreasing viral load or clinical improvement. Secondary outcomes included overall survival and safety of VST infusion, in particular association with graft‐versus‐host disease (GVHD). Results: Ten patients were included, of whom four were treated for ADV, five for CMV, and one for ADV‐CMV‐coinfection. Cells were derived from stem cell donors (6/10) or third‐party donors (4/10). Response criteria were met by six of 10 patients (4/4 ADV, 2/5 CMV, and 0/1 ADV‐CMV). Overall survival was 40%. No infusion related adverse events were documented. Aggravation of GVHD after adoptive immunotherapy was observed in two cases, however in temporal association with a conventional donor lymphocyte infusion and a stem cell boost, respectively. Conclusion: In this cohort, CMV‐ and ADV‐specific T‐cell therapy appear to be safe and effective. We describe the first reported case of virus‐specific T‐cell therapy for CMV reactivation not associated with transplantation but with advanced HIV infection. This encourages further evaluation of adoptive immunotherapy beyond the context of allo‐HCT. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) mismatched, donor IgG‐positive/recipient IgG‐negative, solid organ transplant recipients (SOTRs) are at high risk of CMV invasive disease. Post‐prophylaxis disease is an issue in this population. Some programs employ surveillance after prophylaxis (SAP) to limit the incidence of post‐prophylaxis disease. Methods: This was a single‐center retrospective cohort study that included all CMV mismatched SOTRs from 2003 to 2017. Patients underwent SAP with weekly CMV plasma viral load for 12 weeks. The subjects were classified into three post‐prophylaxis DNAemia patterns: no DNAemia, one episode of DNAemia, and multiple episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also determined 5‐year mortality based on DNAemia pattern stratified by organ transplant type. Results: Post‐prophylaxis recurrent DNAemia occurred in 63% of lung recipients and 32% of non‐lung recipients (p =.003). Tissue invasive CMV disease was diagnosed in 3% of the population and CMV syndrome was diagnosed in 33%. Recurrent DNAemia was not associated with 5‐year mortality. Conclusion: In this cohort, undergoing SAP tissue invasive disease was uncommon and CMV DNAemia recurrence did not have an impact on long‐term mortality. [ABSTRACT FROM AUTHOR]

Background: Valganciclovir prophylaxis against cytomegalovirus (CMV) is recommended for solid organ transplant recipients, but is associated with drawbacks, including expense and leukopenia. Our center adopted a strategy of serial assessment with a CMV‐specific T cell immunity panel (CMV‐TCIP) and cessation of valganciclovir prophylaxis upon demonstration of adequate CD4+ responses in kidney transplant patients at high risk of CMV disease. Methods: We retrospectively reviewed adult recipients of a kidney or pancreas transplant between August 2019 and July 2021 undergoing serial CMV‐TCIP monitoring. Included patients were considered high risk for CMV, defined by donor positive (D+)/recipient negative (R−) CMV IgG serostatus, or recipient positive (R+) patients who received induction with a lymphocyte‐depleting agent. Prophylaxis was discontinued after a patient's first CMV‐specific CD4+ T cell value of ≥0.20%. Risk of clinically significant CMV infection (csCMVi) in those who underwent early discontinuation of CMV prophylaxis and predictors of CMV T cell immunity were analyzed. Results: Of 54 included patients, 22 stopped prophylaxis early due to CMV‐specific CD4+ T cell immunity at a median of 4.7 (IQR: 3.8–5.4) months after transplant. No instances of csCMVi were observed in the 22 patients who had prophylaxis discontinued early, of whom 19/22 were CMV R+ and 3/22 were CMV D+/R−. Donor/recipient CMV serostatus was predictive of immunity (p <.001). Conclusion: Early discontinuation of valganciclovir prophylaxis in patients with CMV CD4+ T cellular immunity appears safe and potentially beneficial in this preliminary series, especially in R+ patients. Further study is warranted, given that truncated prophylaxis may yield patient‐level benefits. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the indications for maternal TORCH (Toxoplasma gondii, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)) serology, with a focus on the yield in isolated fetal growth restriction (FGR). Materials and Methods: A retrospective review of antenatal TORCH testing between January 2014 and December 2018 was carried out at two hospitals in Melbourne, Australia. TORCH testing ordered for pregnancy losses and stillbirth was excluded. Results: Medical records of 718 pregnancies were reviewed, representing 760 fetuses. Isolated FGR was the indication for TORCH screening in 71.2% of pregnancies. Screens ordered for isolated FGR were positive in 7.4% (95% CI 5.5–10.0%). There were 49 positive maternal immunoglobulin M (CMV = 34, Toxoplasma = 15). Two acute maternal infections during pregnancy were diagnosed (CMV = 1, Toxoplasma = 1), with both screens ordered to assess symptomatic maternal illness. There was one neonatal CMV infection, born to a woman with symptomatic primary CMV. No maternal or neonatal rubella or HSV infections were identified. We found a diagnostic yield of TORCH screening for isolated FGR of 0.0% (95% CI 0.00–0.8%). An estimated AUD$64 269.75 was expended on maternal TORCH screens in this study. Conclusion: Maternal TORCH testing for isolated FGR is of no diagnostic yield and should be abandoned. [ABSTRACT FROM AUTHOR]

L'infection congénitale à cytomégalovirus (CMV) est la cause infectieuse la plus fréquente de handicap neurosensoriel congénital. Au cours de la grossesse, il existe différents temps de prévention permettant de réduire les atteintes liées au CMV. La sensibilisation aux mesures d'hygiène préventives doit être mise en œuvre dès la période préconceptionnelle et le plus tôt possible pendant la grossesse afin de limiter les primo-infections et les réinfections à CMV. Ces dernières années, la grande nouveauté dans la prise en charge des infections maternelles primaires à CMV, consiste en l'utilisation du valaciclovir en prévention de la transmission materno-fœtale. Plusieurs études univoques mettent en évidence une réduction du taux de transmission au fœtus de près de 60 à 70 % après séroconversion du premier trimestre de la grossesse grâce à l'instauration rapide du traitement maternel par valaciclovir. Ces nouvelles données viennent donc relancer le débat sur le dépistage systématique du CMV. Congenital cytomegalovirus (CMV) infection is the leading cause of congenital neurosensorial disability. During pregnancy, various timing measures are available to reduce CMV-related harm. Sensitization to preventive hygiene measures should be implemented during the preconception period and as early as possible during pregnancy to limit primary and secondary CMV infections. In recent years, a significant development in the management of primary maternal CMV infections has been the use of valaciclovir to prevent maternal–fetal transmission. Several studies have shown a reduction in the fetal transmission rate of nearly 60 to 70% after seroconversion in the first trimester of pregnancy. These new findings, therefore, rekindle the debate on systematic CMV screening. [ABSTRACT FROM AUTHOR]

Background: Letermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R−) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here. Methods: In this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R−, D+/R+, and D−/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee. Results: Among 22 participants (12 were D+/R−) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R− participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52. Conclusion: Letermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs. Trial registration: ClinicalTrials.gov NCT04129398. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. Methods: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. Results: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). Conclusions: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is common and often self‐limited. Reactivation results in a variety of disease presentations, especially in the setting of immunocompromise. While cutaneous manifestations of systemic CMV infection are rare, dermatologic manifestations of CMV are increasingly reported with a wide morphologic spectrum clinically. Three male patients, with untreated human immunodeficiency virus (HIV), penile lichenoid dermatitis treated with long‐term topical and intralesional corticosteroids, and metastatic Merkel cell carcinoma on immune checkpoint inhibitor therapy, each presented with isolated cutaneous ulcers. The ulcers were located on the perianal skin, glans of the penis, and distal thumb. In each case, nonspecific histopathologic features were seen. However, very rare dermal cytomegalic cells with nuclear and cytoplasmic inclusions were present and highlighted with an immunohistochemical stain for CMV. Isolated ulcers due to CMV infection may occur in the setting of systemic or localized immunosuppression. A high index of suspicion is needed upon histopathologic evaluation, as few cytomegalic cells may be present and accurate diagnosis is crucial for prompt and appropriate clinical management. [ABSTRACT FROM AUTHOR]

Background: Acquired human cytomegalovirus (CMV) is a noteworthy disease in infants. This case study will highlight the influence of early diagnosis of CMV retinitis (CMVR) on avoid visual impairment. Clinical Findings: We describe a preterm female infant with a birth weight of 2060 gr that was admitted for tracheostomy placement due to hypoxic-ischemic encephalopathy. There were no signs of CMV infection or sepsis in laboratory results upon admission such as serology (IgG, IgM antibodies), Toxoplasma gondii, Rubella virus, Herpes simplex virus, CMVR and urine polymerase chain reaction (PCR). Primary Diagnosis: Incidentally, upon screening for retinopathy of prematurity, diffuse occlusive vasculitis was detected in the retinal image on the 112th day of life. Intervention: Intravenous and intraocular ganciclovir were administered for 4 weeks. Outcomes: In the follow-up visit 6 weeks after discharge from the hospital, visual impairment was detected on both sides. Practice Recommendations: This is a report of a case of acquired CMVR, a silent finding, as an uncommon complication in preterm neonates during the hospital stay. This diagnosis should be taken into consideration in preterm infants, since early diagnosis and treatment are crucial to avoid visual impairment. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV)-specific cell-mediated immunity is important for control of CMV after transplant. Assays exist to measure this, but their place in therapy is unclear, particularly in CMV high-risk recipients, without pretransplant exposure. Objective: The objective of this study was to evaluate predictive potential of a positive assay to determine freedom from DNAemia and describe subsequent 3-month CMV outcomes. Methods: Adult CMV high-risk kidney and/or pancreas transplant recipients were included if a CMV inSIGHT T Cell Immunity Panel (TCIP, Eurofins Viracor) was ordered and resulted between 1 August, 2019 and 30 July, 2022. Results: Seventy-six patients were included in our study; 49 tested during prophylaxis and 27 during treatment. Most TCIP assays obtained in the prophylaxis cohort were negative (n = 46, 93.9%). Rate of post-TCIP CMV infection was 10.2%. In those tested during treatment, 33.3% were positive and rate of post-TCIP CMV recurrence was 22.2%. The positive predictive value of the assay to successfully predict immunity was 66.7% during both prophylaxis and treatment. There were 4 cases of TCIP predictive failure with progressive CMV replication. At time of replication, 2 patients had concomitant clinical confounders thought to influence immune control of viral replication. All patients had intensification of immunosuppression prior to recurrent replication, but after TCIP was collected. Conclusion and Relevance: The data obtained from the TCIP are not static, immune control of CMV in latency can change and must be evaluated in clinical context. Timing of TCIP after transplant is significant, and patient-specific factors remain important to assess the likelihood of CMV in each unique patient-specific scenario. A CMV stewardship program can aid in application and interpretation of results. [ABSTRACT FROM AUTHOR]

Introduction: Dyskeratosis congenita is a rare genetic disorder characterized by abnormalities of the skin, nails, and oral mucosa. Retinal involvement in this condition is uncommon. Here, we present a case of a young male patient diagnosed with presumptive cytomegalovirus retinitis, ultimately found to be concomitant with dyskeratosis congenita. Case Presentation: A non-HIV-infected young male with recurrent infections, including aspergillus pneumonia and pneumocystis pneumonia, presented with presumptive cytomegalovirus retinitis in both eyes. Systemic manifestations included cutaneous hyperpigmentation, nail dystrophy, and oral mucosal leukoplakia. Genetic testing revealed a mutation in the DKC1 gene. The final diagnosis was dyskeratosis congenita complicated by presumptive cytomegalovirus retinitis. Conclusion: Cytomegalovirus retinitis can serve as an ocular complication of dyskeratosis congenita. When a patient presents with cytomegalovirus retinitis, a comprehensive systematic examination should be conducted as it indicates severe immunodeficiency. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. Case presentation: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella. Conclusion: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard‐of‐care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV).Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D‐/R‐), survived <90 days post‐LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 109/L), severe leukopenia (WBC ≤ 2.0 × 109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte‐colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post‐PPX CMV infection.204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non‐lymphocyte‐depleting induction (96.6%) and moderate‐risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post‐transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post‐PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high‐risk serostatus showed similar trends, though did not reach statistical significance.In this single‐center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post‐PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX. [ABSTRACT FROM AUTHOR]

The complement system is an evolutionarily ancient component of innate immunity that serves as an important first line of defense against pathogens, including viruses. In response to infection, the complement system can be activated by three distinct yet converging pathways (classical, lectin, and alternative) capable of engaging multiple antiviral host responses to confront acute, chronic, and recurrent viral infections. Complement can exert profound antiviral effects via multiple mechanisms including the induction of inflammation and chemotaxis to sites of infection, neutralization/opsonization of viruses and virally infected cells, and it can even shape adaptive immune responses. With millions of years of co-evolution and the ability to establish life-long infections, herpesviruses have evolved unique mechanisms to counter complement-mediated antiviral defenses, thus enabling their survival and replication within humans. This review aims to comprehensively summarize how human herpesviruses engage with the complement system and highlight our understanding of the role of complement in human cytomegalovirus (HCMV) infection, immunity, and viral replication. Herein we describe the novel and unorthodox roles of complement proteins beyond their roles in innate immunity and discuss gaps in knowledge and future directions of complement and HCMV research. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). Targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, the inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference < 10th centile, failed hearing screen, and prematurity. During the first three years of use of this program (2021–2023), 940 (12.3%) of 7651 live-born infants were tested. The most common indication was birthweight < 10th centile (n = 633, 67.3%). Eleven neonates were diagnosed as congenitally infected, for a prevalence of 1.17% (95%CI 0.48–1.86) on tested neonates and of 0.14% (95%CI 0.06–0.23) on live-born infants. None of the cCMV-infected newborns had a failed hearing screen as a testing indication. Implementation of an expanded cCMV screening program appears feasible and of clinical value. [ABSTRACT FROM AUTHOR]

The article briefed on the epidemiological features of cytomegalovirus infection and shared the successes and experiences of studying these diseases in recent years. Cytomegaly is an infectious disease of viral origin that is fairly common and its manifestations can range from symptomatic forms of internal organs and the central nervous system to severe injuries. The detection of symptoms of cytomegaly in newborns confirms that the fetus is infected inside the uterus. The presence of cytomegalovirus in the mating of an infected newborn proves that infection occurs through the mating. However, the receipt of cytomegaloviruses from the skin and muscle of the embryo excluded through the surgical procedure, and samples made from the lungs and kidneys of the embryo perpetrated on their own, means that the fetus is infected through ciftia in the womb. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We encountered an extremely low birth weight infant with breast milk‐transmitted cytomegalovirus (CMV) infection. To determine the transmission route, we conducted direct sequence analysis of two variable CMV genes, UL139, and UL146. When utilizing breast milk, the possibility of acquired CMV infection should be considered and tested for prompt diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. Methods: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. Results: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). Conclusion: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease. [ABSTRACT FROM AUTHOR]

To report a rare case of cytomegalovirus (CMV)-associated non-necrotizing viral retinopathy, occlusive retinal vasculitis, papillitis, and retinal neovascularization in a young 41-year-old woman. Case report. The patient presented with features of papillitis, peripapillary cotton-wool spots, pre-retinal hemorrhages, and occlusive vasculitis. Her visual acuity was 20/100 in the left eye. She developed a worsening of the disease upon initiation of systemic corticosteroids. Her serum immunoglobulins (Ig) (both IgG and IgM) were highly positive for CMV. Anterior chamber paracentesis was positive for CMV DNA using real-time polymerase chain reaction. After stopping systemic corticosteroids, she was initiated on oral valganciclovir, with rapid resolution of the vasculitis and cotton-wool spots. After three months, the patient developed retinal neovascularization and underwent pan-retinal photocoagulation. However, her uveitis was inactive, and her visual acuity improved to 20/25. Non-necrotizing viral retinopathy has been associated with either varicella zoster virus (VZV) or herpes simplex virus (HSV). Our case highlights that CMV can also lead to non-necrotizing retinopathy and must be suspected in patients who may be negative for VZV and HSV. Appropriate anti-viral treatment can prevent severe vision loss in these patients. [ABSTRACT FROM AUTHOR]

To present the process from acute Posner-Schlossman syndrome (PSS) relapse to remission under 2% ganciclovir (GCV), corticosteroids and anti-glaucoma agents on 323 patients. A retrospective study enrolling 323 PSS patients. Demographics and ophthalmic examination results were generated. Patients were treated with GCV, corticosteroids and anti-glaucoma agents andfollowed up every 2–6 weeks. Patients were divided into the GCV monotherapy (N = 65, 20.12%), GCV and corticosteroids (G+C, N = 106) and GCV, corticosteroid and IOP-lowering drugs (G+C+L, N = 152) group. The G+C+L group had the highest intraocular pressure (IOP, 26.33 ± 10.26 mmHg, P < 0.001) and largest cup-to-disc ratio (0.58 ± 0.19, P < 0.05). After treatment, IOP of three groups dropped to similar level. Ninety-nine (30.65%) patients were corticosteroid-dependent whose daily corticosteroid consumption decreased after using GCV (from 2.23 ± 1.02 to 0.97 ± 0.98 drops/day). 2% GCV solutions worked effectively on PSS relapse with corticosteroids and anti-glaucoma agents. In patients suspected of CMV infection, proper GCV could reduce the chance of corticosteroid dependence. [ABSTRACT FROM AUTHOR]

To report a case series of human immunodeficiency virus (HIV)-negative patients with healed cytomegalovirus retinitis presenting with proliferative retinopathy (in the form of neovascularisation elsewhere). Retrospective case series. Multimodal imaging was performed at each follow-up visit. Three patients with non-HIV immune dysfunction were followed up after healing of CMV retinitis. All three developed neovascularisation. Patient 1 after 4 months presented with vitreous haemorrhage for which pars plana vitrectomy was performed. Patient 2 developed neovascularization at disc and neovascularisation elsewhere 4 months after resolution, and patient 3 despite being affected by bilateral CMV retinitis, presented with unilateral neovascularization at 14 month after resolution of retinitis. Increased incidence of this rare entity could be attributed to partial immune dysfunction in non-HIV patients, limited area of retinitis with a more aggressive occlusive vasculitis. Extensive occlusion with more area of viable retina for angiogenic factor production explains this phenomena. It emphasizes the need for continued follow-up even after healing and to differentiate it from reactivation of retinitis and immune recovery uveitis.Abbreviation: CMV: cytomegalovirus; HIV: human immunodeficiency virus; BCVA: best corrected visual acuity [ABSTRACT FROM AUTHOR]

To investigate predisposing immunosuppressive conditions causing cytomegalovirus retinitis (CMVr) and risk factors for delayed diagnosis in patients diagnosed between 2008 and 2018 in the Swedish population of 10 million. Sixty-three consecutive patients (100 eyes) were diagnosed with CMVr. The most common immunosuppressive state predisposing for CMVr was hematopoietic stem cell transplant recipients (27%) and hematological malignancy (24%). Two patients (3.2%) had no other predisposing factor than diabetes mellitus (DM). Patients with delayed diagnosis (≤30 days) were older than those with earlier diagnosis, mean age 68.7 (±9.8) and 48.8 (±17.6), respectively, p =.001. Signs of intraocular inflammation (IOI) were seen in 42 (70%) of cases and more common in delayed than early diagnosis, 16 (89%) and 21 (60%) respectively (p =.03). Delayed diagnosis was more common in older individuals with signs of IOI. DM may be a risk factor for CMVr, and clinical signs can be mistaken for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection and disease is a condition usually described in immunocompromised patients, but among them, those with connective tissue diseases are poorly represented. Here we present the clinical, laboratory characteristics, management and outcomes of systemic lupus erythematosus (SLE) patients who presented with a CMV infection/disease to a high complexity hospital in southwestern Colombia between 2011 and 2020. 16 SLE patients were found to have a CMV infection. SLE was predominantly characterized by renal involvement (10 patients; 62.50%), and 14 patients (87.5%) were receiving steroids previous to the CMV infection. The entire sample required hospital admission, mainly related to acute kidney injury, and nine patients were admitted to the intensive care unit (ICU). Gastrointestinal organ damage was the most common CMV disease manifestation. All patients received ganciclovir, five of them (31.25%) suffered from septic shock, and seven (43.75%) died. Age ≥38 years and the presence of septic shock at admission were correlated to the mortality outcome. To our knowledge, this is the first publication evaluating SLE patients with CMV infection/disease in a Colombian population. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus–) undergoing repeat keratoplasty. Methods: This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. Results: Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus– group (29%) (P < 0.001). CMV infection in the cornea increased the risk of repeat graft failure and shortened the median survival time (hazard ratio, 3.876; 95% confidence intervals, 2.554–5.884; P < 0.001). The characteristics of graft failure included exacerbation of ocular surface inflammation, neovascularization, and opacification. Epithelial defects, high IOP, and endothelial decompensation were observed at an increased frequency in the CMV+ group (all P < 0.005). Recurrent CMV infection presented as early endothelial infection in the CMV+ group. Recurrence of CMV infection was confined to the graft endothelium without involving the stroma and epithelium post-repeat endothelial keratoplasty. Conclusions: CMV infection post-keratoplasty leads to persistent endothelial damage and graft opacification and significantly increases the risk of repeat graft failure. Localized recurrence of CMV infection in the endothelial grafts underscores the importance of monitoring and treatment. Trial Registration: Chictr.org.cn, ChiCTR1800014684. [ABSTRACT FROM AUTHOR]

Background and Aim: Inner ear infection with some viruses may be one of the possible causes of Sensorineural Hearing Loss (SNHL). This study aims to determine the frequency of Herpes Simplex Virus 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV) in perilymph and peripheral blood samples of cochlear-implanted children. Methods: In this cross-sectional study, 30 children with severe-to-profound SNHL (aged 1.1–5 years) underwent cochlear implantation surgery. During surgery, their perilymph and peripheral blood samples were collected. The samples were analyzed separately for the presence of herpes HSV-1, HSV-2, and CMV by real-time Polymerase Chain Reaction (PCR) method. The load of IgG and IgM antibodies against these viruses was determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: The frequency of CMV in perilymph samples was 16.7% (5 patients) and in peripheral blood samples was 3.3% (1 patient). The IgG antibody against CMV and HSV1 was positive in 80% and 46.7% of the patients, respectively. The IgM antibody against CMV was positive in 10%. The mean IgM serum antibody load against HSV-1, HSV-2, and CMV was 2.70, 1.70, and 5.47, respectively, and the mean IgG antibody load against these viruses was 56.07, 2.50, and 23.67, respectively. Conclusion: The IgG test is positive in cochlear-implanted children with CMV in their perilymph samples, and the CMV genome is not present in their peripheral blood. This may indicate the previous presence of this virus in the ear and its role in hearing loss. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral infections in etiopathogenesis. The aim of this study was to summarize the relationship between viral infections and BPD through a systematic review and meta-analysis. We searched PubMed, Embase, the Web of Science Core Collection, and the Cochrane Database on December 19, 2023. We included observational studies that examined the association between viral infections and BPD in preterm infants. We extracted data on study methods, participant characteristics, exposure assessment, and outcome measures. We assessed study risk of bias using the Newcastle-Ottawa Scale (NOS). We included 17 and 15 studies in the qualitative review and meta-analysis, respectively. The meta-analysis showed a significant association between viral infection and BPD diagnosed at 36 weeks postmenstrual age (odds ratio (OR): 2.42, 95% confidence interval: 1.89–3.09, 13 studies, very low certainty of evidence). In a subgroup analysis of specific viruses, cytomegalovirus (CMV) proved to be significantly associated with BPD diagnosed at 36 weeks postmenstrual age (OR: 2.34, 95% confidence interval: 1.80–3.05, 11 studies). We did not find an association between viral infection and BPD diagnosed on the 28th day of life, probably due to the small sample size of the included prospective studies. Conclusion: Viral infections, especially CMV, are associated with an increased risk of BPD in preterm infants. Methodologically reliable prospective studies with large samples are needed to validate our conclusions, and high-quality randomized controlled studies are needed to explore the effect of prevention or treatment of viral infections on the incidence of BPD. What is Known: • Studies have attempted to identify viral infections and bronchopulmonary dysplasia in preterm infants; however, results have been inconsistent. What is New: • Systematic demonstration that viral infections, particularly cytomegalovirus, are positively associated with bronchopulmonary dysplasia diagnosed in preterm infants at the 36th week of postmenstrual age. • The importance of screening for viral infections in preterm infants, especially cytomegalovirus. More high-quality studies should be produced in the future to investigate the causal relationship between viral infections and bronchopulmonary dysplasia. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of unilateral cytomegalovirus (CMV) panuveitis with occlusive vasculitis after injection of intravitreal dexamethasone implant in a patient with type 2 diabetes mellitus. Methods: Observational case report. Results: A 60-year-old immunocompetent man with well-controlled type 2 diabetes mellitus was treated with intravitreal dexamethasone implant for recurrent uveitis that was responsive to steroids. Three months after implantation, the patient develops panuveitis with occlusive vasculitis. Anterior chamber tap confirms diagnosis of cytomegalovirus retinitis. Intravitreal foscarnet and oral valganciclovir led to quiescent disease. Conclusions: Patients treated with local immunosuppressants should be monitored carefully to assess treatment response and complications, even in the absence of frank immunodeficiency. Quantitative viral PCR can be an effective way to monitor treatment response to antiviral therapy. [ABSTRACT FROM AUTHOR]

We investigated the basic characteristics of a new murine cytomegalovirus (MCMV) vector platform. Using BAC technology, we engineered replication-competent recombinant MCMVs with deletions of up to 26% of the wild-type genome. To this end, we targeted five gene blocks (m01-m17, m106-m109, m129-m141, m144-m158, and m159-m170). BACs featuring deletions from 18% to 26% of the wild-type genome exhibited delayed virus reconstitution, while smaller deletions (up to 16%) demonstrated reconstitution kinetics similar to those of the wild type. Utilizing an innovative methodology, we introduced large genomic DNA segments, up to 35 kbp, along with reporter genes into a newly designed vector with a potential cloning capacity of 46 kbp (Q4). Surprisingly, the insertion of diverse foreign DNAs alleviated the delayed plaque formation phenotype of Q4, and these large inserts remained stable through serial in vitro passages. With reporter-gene-expressing recombinant MCMVs, we successfully transduced not only mouse cell lines but also non-rodent mammalian cells, including those of human, monkey, bovine, and bat origin. Remarkably, even non-mammalian cell lines derived from chickens exhibited successful transduction. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) primary infection, re-infection, and reactivation from latency cause morbidity in immune-compromised patients. Consequently, potential therapeutic strategies remain of interest for the treatment of infection. Naturally occurring triterpenoids derived from plants have been demonstrated to have anti-viral activity, although their precise mechanisms of action are not always fully understood. Here, we investigate the activity of Mormordin Ic (Mc) and demonstrate that it is potently anti-viral against HCMV. Through investigation of the mechanistic basis of this anti-viral activity, we identify that it is inhibitory to both viral and host gene expression, and to highly induced genes in particular. We go on to observe that Mc impacts on RNA Pol II activity and, specifically, reduces the occupancy of elongating RNA Pol II at a viral promoter. Next, we demonstrate that Mc is inhibitory to HCMV reactivation, and in doing so identify that it has greater activity against the canonical major immediate early promoter compared to the alternative ip2 promoter located downstream. Finally, we see evidence of RNA Pol II occupancy at the ip2 promoter in undifferentiated myeloid cells. Thus, Mc is potently anti-viral and a potential tool to probe the activity of multiple promoters considered important for controlling HCMV reactivation. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection poses significant risks in allogeneic haematopoietic stem cell transplant (allo‐HSCT) recipients. Despite advances in antiviral therapies, issues such as drug resistance, side effects, and inadequate immune reconstitution remain. This systematic review and meta‐analysis aim to evaluate the efficacy and safety of adoptive cell therapy (ATC) in managing CMV infections in allo‐HSCT recipients. Adhering to preferred reporting items for systematic reviews and meta‐analyses guidelines, we conducted a comprehensive database search through July 2023. A systematic review and meta‐analysis were conducted on studies involving HSCT patients with CMV infections treated with ATC. The primary outcome was the response rate to ATC, and secondary outcomes included adverse events associated with ATC. The Freeman–Tukey transformation was applied for analysis. In the meta‐analysis of 40 studies involving 953 participants, ATC achieved an overall integrated response rate of 90.16%, with a complete response of 82.59% and a partial response of 22.95%. ATC source, HLA matching, steroid intake, and age group markedly influenced response rates. Donor‐derived T‐cell treatments exhibited a higher response rate (93.66%) compared to third‐party sources (88.94%). HLA‐matched patients demonstrated a response rate of 92.90%, while mismatched patients had a lower rate. Children showed a response rate of 83.40%, while adults had a notably higher rate of 98.46%. Adverse events were minimal, with graft‐versus‐host disease occurring in 24.32% of patients. ATC shows promising response rates in treating CMV infections post‐HSCT, with an acceptable safety profile. However, to establish its efficacy conclusively and compare it with other antiviral treatments, randomised controlled trials are essential. Further research should prioritise such trials over observational and one‐arm studies to provide robust evidence for clinical decision‐making. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodResultsLimitationsImplicationsInformation related to herpes simplex virus 1 and 2 (HSV-1 and 2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) seroprevalence in France is either lacking, incomplete, or outdated, despite their public health burden.We used routinely collected serological data between 2018 and 2022 to estimate HSV-1, HSV-2, VZV, EBV, and CMV seroprevalence in France. To account for demographic differences between our analytic samples and the French population and get estimates for sparsely sampled districts and age classes, we used a multilevel regression and poststratification approach combined with Bayesian model averaging via stacking weights.The observed seroprevalence (number of positive tests/number of tests) were 64.6% (93,294/144,424), 16.9% (24,316/144,159), 93.0% (141,419/152,084), 83.4% (63,199/75, 781), and 49.0% (23,276/47,525), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV. Between 2018 and 2022, France had a model-based average (equal-tailed interval at 95%) expected seroprevalence equal to 61.1% (60.7,61.5), 14.5% (14.2,14.81), 89.5% (89.3,89.8), 85.6% (85.2,86.0), and 50.5% (49.3,51.7), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV infections. We found an almost certain lower expected seroprevalence in Metropolitan France than in overseas territories for all viruses but VZV, for which it was almost certainly greater. The expected seroprevalences were likely greater among females for all viruses.Our results relied on the assumption that individuals were sampled at random conditionally to variables used to build the poststratification table.The analysis highlights spatial and demographic patterns in seroprevalence that should be considered for designing tailored public health policies. [ABSTRACT FROM AUTHOR]

AbstractAlemtuzumab is a potent lymphocyte-depleting immunotherapy used in solid organ transplan­tation (SOT), that is increasingly being applied in diverse lymphoproliferative disorders (LPDs). However, a significant toxicity limiting expanded usage is cytomegalovirus (CMV) infection, for which standardized preventive strategies exist in SOT but not in LPDs due to a poor understanding of infection risk in this population, with early LPD studies largely limited to stem cell transplantation. Using one of the most diverse arrays of LPDs studied to date, our retrospective cohort study of non-transplant patients receiving alemtuzumab over a ten-year period at a large regional cancer center examines the incidence and clinical profile of infected patients. Among 24 patients, we identified a composite CMV infection rate of 42% with a symptomatic rate of 21%. We also noted significant variations in preventive strategies, which alongside a high infection rate presents an opportunity to improve outcomes through further work in standardization. [ABSTRACT FROM AUTHOR]

Hypereosinophilia is a rare presentation in all age groups, particularly when it is severe, persistent, and progressive. We describe the clinical characteristics and course of severe hypereosinophilia in a full-term Saudi female neonate. A febrile respiratory illness evolved with a progressive increase in peripheral blood leukocyte and eosinophil counts, reaching 44.9% of leukocytes and an absolute value of 57,000 cells/µl. Different etiological examinations (for viral, bacterial, immunodeficiency, hyper IgE syndrome, gene mutations) revealed extremely high CMV antigenemia and a homozygous mutation in the STAT1 gene. Anhelation was relieved by oxygen and anti-viral treatment. Steroids brought a dramatic response in peripheral blood counts within 24 h. After a 6-week course of antiviral and steroid treatment at home, she had an excellent general condition. Conclusion: Although a rare pathology, it is important to consider genetic disorders when there is an atypical immune response to viral infections. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) reactivation is a significant concern following allogeneic stem cell transplantation. While previous research has highlighted the anti-CMV reactivation effect of γδ T cells in immunocompromised transplant patients, their characterization in recipients at high risk of CMV reactivation remains limited. Methods: This study focused on D+/R+ recipients (where both donor and recipient are CMV seropositive) at high risk of CMV reactivation. We analyzed 28 patients who experienced CMV recurrence within 100 days post-allogeneic hematopoietic stem cell transplantation, along with 36 matched recipients who did not experience CMV recurrence. Clinical data from both groups were compared, and risk factors for CMV reactivation were identified. Additionally, CMV viral load was measured, and flow cytometric analysis was conducted to assess changes in peripheral blood γδ T cell proportions, subpopulation distribution, and differentiation status. We also analyzed the CDR3 repertoire of the TCR δ chain in different γδ T cell subsets. Functional analysis was performed by measuring the lysis of CMV-infected cells upon stimulation. Results: CMV reactivation post-transplantation was associated with acute graft-versus-host disease (aGvHD) and reactivation of non-CMV herpesviruses. Notably, CMV reactivation led to sustained expansion of γδ T cells, primarily within the Vδ2neg γδ T cell subpopulation, with a trend toward differentiation from Naive to effector memory cells. Analysis of the δ chain CDR3 repertoire revealed a delay in the reconstitution of clonal diversity in Vδ2neg γδ T cells following CMV reactivation, while Vδ2pos T cells remained unaffected. Upon stimulation with CMV-infected MRC5 cells, the Vδ2neg γδ T cell subpopulation emerged as the primary effector cell group producing IFN-γ and capable of lysing CMV-infected cells. Moreover, our findings suggest that NKG2D is not necessary involved in Vδ2neg γδ T cell-mediated anti-CMV cytotoxicity. Conclusion: This study provides novel insights into the role of γδ T cells in the immune response to CMV reactivation in transplantation recipients at high risk of CMV infection. Specifically, the Vδ2neg γδ T cell subpopulation appears to be closely associated with CMV reactivation, underscoring their potential role in controlling infection and reflecting CMV reactivation in HSCT patients. [ABSTRACT FROM AUTHOR]

Letermovir, a novel anti‐cytomegalovirus (CMV) agent acts by inhibiting the viral terminase complex and is approved for primary prophylaxis in CMV seropositive patients post allogeneic hematopoietic cell transplantation (HCT). The favorable efficacy and safety profile make it an attractive option for use as secondary prophylaxis in patients at high‐risk for CMV reactivation. In this study, we report the efficacy and safety of letermovir secondary prophylaxis after at least one treated episode of CMV reactivation in a cohort of 39 high‐risk patients. Thirty two (82%) patients received anti‐thymocyte globulin (ATG), 27 (69%) received a combination of ATG and post‐transplant cyclophosphamide for graft‐versus‐host disease (GVHD) prophylaxis. Twenty one patients (54%) received CMV seronegative grafts. In addition, 18 (46%) patients had HLA mismatched unrelated or haploidentical donors while 18 (46%) had active GVHD requiring immunosuppression at the time of commencing secondary prophylaxis. Letermovir was initiated at a median of 47 days (range, 41–56) after HCT and was administered for a median duration of 77 days (range, 46–90). A single breakthrough CMV reactivation was noted in this high‐risk cohort. Four additional episodes of CMV reactivation occurred at a median of 28 days (range, 23–59 days) after discontinuation of secondary prophylaxis. The drug was well tolerated and 77% of the cohort completed the planned duration of secondary prophylaxis. None of the patients discontinued treatment due to treatment‐related adverse effects. In conclusion, letermovir is effective and well tolerated and may be considered for secondary prophylaxis in patients at high risk for CMV reactivation. Prospective studies are required to validate these findings. [ABSTRACT FROM AUTHOR]