Cytomegalovirus Research Articles

Predictive Factors of Cytomegalovirus Colonic Reactivation in Patients with Active Ulcerative Colitis

Cytomegalovirus (CMV)-associated colitis reflects the adverse impact of CMV reactivation on ulcerative colitis (UC). Its diagnosis requires the detection of viral markers in intestinal biopsies sampled during endoscopy, which may constitute invasive and expensive analyses. Moreover, less than 30% of acute flare-ups in steroid refractory UC are associated with CMV colitis. This retrospective study aimed to identify non-invasive factors that are predictive of CMV reactivation, and was conducted from 2014 to 2019 in a cohort of UC patients consulting at the University Hospital of Saint-Etienne, France. Patient characteristics, disease activity, immunosuppressive treatment and tissue CMV DNA load were collected at the time of UC relapse. Factors potentially associated with CMV reactivation were analyzed through a multivariate analysis. A total of 173 UC patients providing 323 pairs of intestinal biopsies were analyzed. In the CMV seropositive subgroup, a Mayo endoscopic score ≥2 (OR 2.553, 95% CI 1.353–4.818, p = 0.004) was identified as a predictive factor of CMV colitis in the multivariate analysis; in contrast, biological parameters exhibited no predictive value. In addition, the use of anti-TNFα monoclonal antibodies was associated with a reduced risk of CMV reactivation (OR 0.384, 95% CI 0.158–0.935, p = 0.035). Intestinal biopsies appear to be unavoidable for assessing disease activity and CMV reactivation in UC patients.

Gastrointestinal cytomegalovirus infection in persons with HIV: a retrospective case series study

BackgroundGastrointestinal (GI) cytomegalovirus (CMV) infection remains an important cause of morbidity among persons with HIV (PWH), even in the late antiretroviral therapy (ART) era. However, its varied clinical presentations and outcomes are not fully understood.MethodsWe conducted a retrospective review of 21 PWH with histologically confirmed GI-CMV infections admitted to a tertiary hospital in Nanjing, China, between September 2018 and September 2023. Clinical features, endoscopic findings, histology, treatment responses, and outcomes were examined.ResultsPatients were predominantly male (95.2%) with a median age of 42 years. Over 80% had CD4 cell counts below 50 cells/µL; at admission, they were not on effective ART or had only recently initiated it, with a median HIV viral load of 5.2 log copies/mL (IQR: 4.9–5.7). Diarrhea (71.4%) was the most common presentation, followed by fever (52.4%), abdominal pain (47.6%), and GI bleeding (38.1%). The median symptom duration was 2.0 months (IQR: 1.0–5.0). Nearly half the patients had concurrent CMV end-organ disease—most commonly CMV retinitis—and 95.2% had at least one AIDS-defining illness; GI mycobacterial co-infection was found in three patients. The colon was the most frequently affected GI site, followed by the stomach and esophagus. Endoscopic findings included ulcers, erosions, proliferative lesions, and diffuse mucosal hemorrhage. All patients initially received intravenous ganciclovir and/or foscarnet for a median of 30 days (IQR: 20–39). The 9 patients with CMV retinitis were given oral ganciclovir maintenance. Gastrointestinal surgery was needed in 9.5% of cases. The 6-month mortality rate was 4.8%.ConclusionGI-CMV infection primarily affects PWH with profound immunosuppression (CD4 < 50 cells/µL) and inadequate or absent ART. These patients frequently have other AIDS-defining illnesses and CMV end-organ diseases, complicating their management. For PWH with GI-CMV infection, clinicians should address not only CMV itself but also coexisting conditions arising from advanced immunodeficiency to improve outcomes.

Contribution of Sorting Nexin 3 in the Cytomegalovirus Assembly

Background/Objectives: Cytomegalovirus (CMV) infection expands early endosomes (EEs) into tubular extensions that may contribute to the control of virus replication and virion assembly. Sequential recruitment of protein coats and sorting nexins (SNXs) creates membrane zones at the EEs that serve as scaffolds for membrane tubulation and retrieval of cargo proteins, including host cell signaling proteins and viral glycoproteins. This study aims to investigate whether the SNX3-dependent zone of EEs contributes to CMV replication and assembly. Methods: Protein localization was analyzed by confocal imaging and expression by Western blot. The contribution of SNX3 to murine CMV (MCMV) replication, assembly compartment (AC) formation, and virion release was analyzed by siRNA and shRNA depletion. The impact of other downstream SNXs that act in EE tubulation was investigated by combined siRNA knockdowns of SNX1, SNX2, SNX4, SNX17, and SNX27 on cell lines expressing shRNA for SNX3. Results: The SNX3-162 isoform acting at EEs was efficiently knocked down by siRNA and shRNA. The SNX3-dependent EE zone recruited SNX27 and contributed to Rab10-dependent tubulation within the pre-AC. SNX3 was not essential for MCMV replication but contributed to the SNX27-, SNX17- and SNX4-dependent release of virions. Silencing SNX3 further reduced the release of virions after silencing SNX27, SNX4, and SNX17, three SNXs that control recycling to the plasma membrane. Conclusions: SNX3 contributes to the formation of pre-AC and MCMV assembly. It acts sequentially with SNX27, SNX4, and SNX17 along the recycling pathway in the process of the production and release of infection virions, suggesting that multiple membrane sources may contribute to the secondary envelopment of MCMV virions.

Prevalence and clinical manifestations of cytomegalovirus infection in patients with Posner-Schlossman syndrome: A systematic review and meta-analysis.

Prevalence and clinical manifestations of cytomegalovirus infection in patients with Posner-Schlossman syndrome: A systematic review and meta-analysis.

Awareness and knowledge of cytomegalovirus infection among pregnant women in French-speaking Switzerland

BackgroundIn Switzerland, cytomegalovirus (CMV) is the most common congenital infection, affecting more than 400 newborns per year. It is also the leading non-genetic cause of neurosensory impairment in children. The aims of this study were to assess the awareness, general knowledge and knowledge of hygiene measures related to CMV among pregnant women in French-speaking Switzerland, as well as identify baseline characteristics potentially associated with a better knowledge of CMV.MethodsA regional cross-sectionnal study carried out in French-speaking Switzerland between May and December 2022, using a 36-item questionnaire available through a QR code.ResultsThe majority of pregnant women surveyed, 61.6% (514/834), had already heard about CMV. Half the participants (50.4%, 375/743) knew how to protect themselves against this infection. Only 7.2% (60/834) were aware of all the consequences of congenital CMV infection in newborns, and only 1.2% (10/834) knew all the general facts about this virus (transmission, screening, treatment, fetal and maternal risks). An education above secondary level and having a high-risk profession (daycare of healthcare providers) appeared to be factors independently associated with greater awareness and knowledge of CMV, and of the hygiene measures to protect against it. Having been followed by a midwife (only or in addition to an obstetrician) was also associated with a greater knowledge of the virus, and age over 30 and being multiparous were also factors independently associated with a better knowledge of hygiene measures to adopt against CMV.ConclusionAwareness of CMV among pregnant women appears to have improved since a previous study conducted in Geneva in 2015. While knowledge of preventive measures among participants was insufficient to ensure comprehensive protection against CMV infection, it represents a significant improvement compared to previous studies. Further efforts are needed to enhance this knowledge to maximize its potential impact on prevention behaviors.

Persistence of CMV-specific anti-HIV CAR T cells after adoptive immunotherapy.

The success of chimeric antigen receptor (CAR)-T cell (Tc) immunotherapy in refractory B-cell acute lymphoblastic leukemia (B-ALL) suggests adaptation of this strategy toward HIV. Because cytomegalovirus (CMV) vaccine vectors generated Tc responses that controlled viral replication, these studies aim to genetically modify CMV-specific Tc with HIV-CAR2 vectors and link HIV immunotherapy to persistent CMV antigen stimulation. To mimic a clinical scenario, rhesus macaques were challenged with the CCR5-tropic simian/human immunodeficiency virus (SHIV-D) prior to antiretroviral therapy (ART). Autologous CMV-specific Tc were transduced with the control CEA-CAR2 or CD4-CAR2/maC46 vectors and reinfused. After stopping ART, the plasma viral load (PVL) in the control rebounded and was sustained above 1.7 × 104 copies/mL; PVL in CD4-CAR2-treated animals was delayed up to 6 weeks and 10-fold lower. The CD4 CAR-Tc frequency peaked at day 7 and was detected in lymphoid tissues at 6 weeks. Both CEA-CAR2 and CD4-CAR2 persisted in PBMCs for about 2 years, which indicates that the CMV-specific CAR Tc were maintained based on their CMV specificity. However, long-term PVL was stable in all animals. Thus, CMV-specific CAR-Tc were active initially, persisted long term, but failed to control viral replication.IMPORTANCEBecause of latent viral reservoirs and a dysfunctional immune response, HIV replication rebounds when antiretroviral therapy is interrupted. Therefore, cytomegalovirus (CMV)-specific Tc were genetically modified with anti-HIV CD4-CAR2 vectors to link the targeting of the HIV envelope to the persistent CMV immune response. In this clinical scenario with simian/human immunodeficiency virus (SHIV) challenge and antiretroviral therapy (ART) suppression, early activity of the CAR Tc delayed rebound in the rhesus macaque/SHIV challenge model. However, even with long-term persistence of CAR Tc in the blood, control of viral replication was not achieved. These data suggest that CAR Tc will require additional interventions to cure HIV infection.

Potential Relationship Between Helicobacter pylori Infection and Autoimmune Disorders: A Narrative Review.

Potential Relationship Between Helicobacter pylori Infection and Autoimmune Disorders: A Narrative Review.

Retrospective Analysis of Hearing Outcomes of Cochlear Implantation in Patients with Deafness Due to Congenital CMV Infection

Cytomegalovirus (CMV) infection in pregnant women is one of the most common causes of congenital infection in children. It is often asymptomatic but can lead to serious complications, including progressive sensorineural hearing loss. Profound hearing loss is an indication for cochlear implantation (CI). Electrode impedance and neural response telemetry (NRT) thresholds can be measured to confirm correct electrode placement and speech processor programming. Background/Objectives: The aim of the study is to evaluate the hearing outcome of children with profound sensorineural hearing loss or deafness due to cCMV infection after CI compared to a control group of children born with other causes of congenital hearing loss and to identify prognostic factors predicting the outcome of patients with hearing loss due to cCMV infection after CI. Methods: A retrospective study was conducted in patients implanted between 2016 and 2023 at the Department of Otolaryngology of the Institute of the Polish Mother’s Memorial Hospital Research Institute in Łódź. Pre- and postoperative hearing levels, electrode impedance and neural response telemetry (NRT) thresholds were compared. The degree of pre-implantation hearing loss was assessed by the level of the recorded V-wave in the ABR test. Post-implantation hearing assessment was based on the last available free-field tonal audiometry measurement. Impedance measurements were included: intraoperative, 1, 6, 12 months after CI, respectively, and NRT thresholds. Results: The final analysis included 84 patients with profound sensorineural hearing loss and complete audiological follow-up data: 13 patients with congenital CMV (cCMV) infection and 71 patients with other causes of deafnes. The analysis included 175 implanted ears: 17 in the CMV group and 158 in the control group. The age at implantation ranged from 1 to 11 years in the CMV and from 1 to 13 years in the control group. Mean preoperative hearing thresholds were 94.54 dB in the CMV group and 97.04 dB in the control group. At the most recent postoperative evaluation, mean thresholds improved to 33.83 dB and 36.42 dB, respectively. No statistically significant differences were observed between the groups. Mean intraoperative NRT values were 79.74 in the CMV group and 86.90 in the non-CMV group. Final NRT values were 129.77 and 130.76, respectively. Mean impedance values measured intraoperatively and at 1, 6 and 12 months postoperatively were 11.09 kOhm, 13.40 kOhm, 8.35 kOhm and 8.25 kOhm in the CMV group; and 12.28 kOhm, 14.06 kOhm, 9.60 kOhm and 8.00 kOhm in the control group, respectively. Conclusions: CI in children with deafness caused by cCMV infection is an effective treatment option. Initial electrical impedance values of the electrodes increase after implant activation and decrease in subsequent months of follow-up, suggesting the absence of active adhesion processes in the cochlea.

Small glycomimetic antagonists of the cytomegalovirus glycoprotein UL141 prevent binding to TRAIL death receptor.

Human cytomegalovirus (HCMV) UL141 inhibits immune recognition of virally infected cells by natural killer (NK) cells and cytotoxic T cells through modulation of cellular receptors (e.g., TRAIL-R2/-R1, CD155, CD112). Recent findings suggest that UL141 is also a critical component of the HCMV virion, that further emphasizing its significance. In this study, we aimed to develop a small synthetic compound as a UL141 antagonist. Building on our crystal structure analysis, we designed compounds to specifically bind viral UL141, thereby blocking its interaction with target receptors thus inhibiting its immunoevasive functions. We evaluated a small library of synthesized compounds composed of diverse saccharide units conjugated with non-saccharide moieties, such as non-ionic glycolipids, pyrrolidines, and 'click' conjugates. An ELISA-like TMB binding assay, coupled with dynabeads coating, was employed to assess the ability of these compounds to inhibit TRAIL-R2 binding in vitro. The most promising compounds capable of inhibiting complex formation were further analyzed using surface plasmon resonance (SPR). Compound 18 exhibited the strongest binding affinity to UL141, with KD of 2.93 μM. Molecular docking studies identified specific binding sites on UL141, and the fragmented molecular orbital (FMO) method was applied to evaluate interaction energy patterns between the antagonist and the UL141 protein. Mutational analysis was conducted to validate the identified binding sites on UL141. Additionally, cellular cytotoxicity assays were performed to confirm the non-toxic properties of these compounds. Collectively, our findings suggest that synthetic glycomimetics represent promising candidates for targeting the viral glycoprotein HCMV UL141, thereby disrupting TRAIL death receptor signaling thus mitigating viral activity.

Efficacy and safety of ROH-101 (0.15% ganciclovir gel) for cytomegalovirus corneal endotheliitis: an open-label, uncontrolled, phase 3 study in Japan.

Cytomegalovirus (CMV) corneal endotheliitis often causes severe visual impairment owing to irreversible corneal endothelial dysfunction. Given the side effects of systemic antiviral therapy, development of an approved topical antiviral agent for CMV corneal endotheliitis is desirable. This study evaluated the efficacy and safety of topical 0.15% GCV gel, ROH-101, in the treatment of CMV corneal endotheliitis in Japanese patients. Open-label, multicenter, uncontrolled, phase 3 study (jRCT2051210064). The study was conducted from August 2021 to December 2022, with a 2-week run-in period with 0.1% fluorometholone eye drops alone, a 12-week treatment period with additional ROH-101, and a 24-week post-treatment observation period after discontinuation of ROH-101. The primary endpoint was the proportion of patients achieving a CMV DNA copy number in the aqueous humor of less than 103 copies/mL at week 12. The clinical findings and safety were assessed over the treatment and post-treatment observation periods. Twelve eyes of 12 patients with PCR-proven CMV corneal endotheliitis were enrolled. Treatment was discontinued in 1 eye owing to an adverse event. The other 11 eyes completed 12 weeks of treatment with 63.6% achieving the primary endpoint. The clinical findings, such as corneal edema, coin-shaped lesions, and anterior chamber inflammation, improved in all 11 eyes and did not worsen in 8 eyes that completed the post-treatment observation period. Endothelial cell density was well maintained, and none of the 11 eyes showed corneal endothelial dysfunction. Mild adverse drug reactions were reported in 3 eyes (8.3%). ROH-101 was a safe and efficacious treatment in Japanese patients diagnosed with CMV corneal endotheliitis.

Molecular cloning and host range analysis of three cytomegaloviruses from Mastomys natalensis.

Herpesvirus-based vectors are attractive for use as conventional or transmissible vaccines against emerging zoonoses in inaccessible animal populations. In both cases, cytomegaloviruses (CMVs) as members of the subfamily Betaherpesvirinae are particularly suitable for vaccine development as they are highly specific for their natural host species, infect a large proportion of their host population, and cause mild infections in healthy individuals. The Natal multimammate mouse (Mastomys natalensis) is the natural reservoir of Lassa virus, which causes deadly hemorrhagic fever in humans. M. natalensis was recently reported to harbor at least three different cytomegaloviruses (MnatCMV1, MnatCMV2, and MnatCMV3). Herein, we report the molecular cloning of three complete MnatCMV genomes in a yeast and bacterial artificial chromosome (YAC-BAC) hybrid vector. Purified viral genomes were cloned in yeast by single-step transformation-associated recombination (STAR cloning) and subsequently transferred to Escherichia coli for further genetic manipulation. The integrity of the complete cloned viral genomes was verified by sequencing, and the replication fitness of viruses reconstituted from these clones was analyzed by replication kinetics in M. natalensis fibroblasts and kidney epithelial cells. We also found that neither parental nor cloned MnatCMVs replicated in mouse and rat fibroblasts, nor did they show sustained replication in baby hamster kidney cells, consistent with the expected narrow host range for these viruses. We further demonstrated that an exogenous sequence can be inserted by BAC-based mutagenesis between open reading frames M25 and m25.1 of MnatCMV2 without affecting replication fitness in vitro, identifying this site as potentially suitable for the insertion of vaccine target antigen genes.IMPORTANCECytomegaloviruses (CMVs) recently discovered in the Natal multimammate mouse (Mastomys natalensis) are widespread within the M. natalensis population. Since these rodents also serve as natural hosts of the human pathogen Lassa virus (LASV), we investigated the potential suitability of M. natalensis CMVs (MnatCMVs) as vaccine vectors. We describe the cloning of three different MnatCMV genomes as bacterial artificial chromosomes (BACs). The replicative capacity and species specificity of these BAC-derived MnatCMVs were analyzed in multiple cell types. We also identified a transgene insertion site within one of the MnatCMV genomes suitable for the incorporation of vaccine target antigens. Together, this study provides a foundation for the development of MnatCMVs as transmissible MnatCMV-based LASV vaccines to reduce LASV prevalence in hard-to-reach M. natalensis populations and, thereby, zoonotic transmission to humans.

Human cytomegalovirus gH/gL/gO binding to PDGFRα provides a regulatory signal activating the fusion protein gB that can be blocked by neutralizing antibodies.

Development of vaccines and therapeutics targeting the fusion apparatus of human cytomegalovirus (HCMV) has been limited by the lack of an in vitro cell-cell fusion assay that faithfully models the receptor-dependent fusion characteristic of HCMV entry. The cell-cell fusion assay described here demonstrated that the binding of gH/gL/gO to its receptor, PDGFRα, serves to regulate the activity of the fusion protein gB, and this is specifically vulnerable to inhibition by neutralizing antibodies. Moreover, the measurement of fusion kinetics allows for mutational studies of the fusion mechanism, assessing the influence of genetic diversity among the viral glycoproteins and studying the mechanism of neutralizing antibodies.

Senescence-related cytokine levels are associated with HIV-1 serostatus and persistence.

HIV-1 infection is associated with accelerated aging. The senescence-associated secretory phenotype (SASP) includes biological and cytokine profiles that induce cellular senescence and inflammaging. In this study, we leveraged the Multicenter AIDS Cohort Study (MACS) to evaluate the role of SASP in aging, HIV-1 reservoir, and inflammation in people with HIV-1 (PWH) on long-term suppressive antiretroviral therapy (ART). In this retrospective study, we included plasma and serum samples from 27 virally suppressed PWH and 10 people without HIV-1 (PWoH) collected in 2019 and 2023. SASP markers were quantified in the 2019 and 2023 samples. Plasma residual viremia, intact and defective proviral DNA were quantified in the 2019 samples. Correlations between SASP markers and HIV-1 reservoir were performed using the Spearman test, and the sparse partial least squares discrimination analysis was used to identify variables that distinguish HIV-1 serostatus. All study participants were male with a median age of 59 years. SASP markers did not show significant changes longitudinally in either group. We identified a set of markers that had moderate performance in distinguishing PWH and PWoH, including cytomegalovirus (CMV) serum antibody titer, matrix metalloproteinase 9 (MMP-9), growth/differentiation factor-15, Stanniocalcin-1 and SerpinE1. Among all the SASP markers, MMP-9 was significantly associated with intact HIV-1 proviral levels [ρ = 0.60, P = 0.002, false detection rate (FDR) = 0.03]. In this cohort study, we revealed the relationship between SASP markers and HIV-1 persistence. Future interventions targeting the senescence pathways may impact HIV-1 persistence.

Standardizing Care and Management of Cytomegalovirus Infections in Solid Organ Transplant Recipients: Highlights From the Fourth Consensus Guidelines.

Standardizing Care and Management of Cytomegalovirus Infections in Solid Organ Transplant Recipients: Highlights From the Fourth Consensus Guidelines.

Epidemiology and Economic Burden of Diagnosed Congenital Cytomegalovirus Infection in the First 2 Years of Life among Commercially Insured and Medicaid-Insured Individuals in the United States.

Epidemiology and Economic Burden of Diagnosed Congenital Cytomegalovirus Infection in the First 2 Years of Life among Commercially Insured and Medicaid-Insured Individuals in the United States.

Case Report: Maribavir for refractory cytomegalovirus viremia after renal transplantation in a child with Schimke’s immune-osseous dysplasia

Cytomegalovirus (CMV) is a major opportunistic pathogen in recipients of solid organ transplantation. Maribavir, a pUL97 protein kinase inhibitor, was approved for the treatment of refractory post-transplant CMV infection in the US in 2021. However, it is rarely used in pediatric patients worldwide. Here, we report the case of a Chinese boy with Schimke’s immune-osseous dysplasia (SIOD) who developed refractory CMV infection after a renal transplantation. An 11-year-old boy was hospitalized with recurrent abdominal and testicular pain 50 days after renal transplantation. Diagnoses included urinary tract infection, epididymitis, CMV viremia, stage 2 chronic kidney disease, and SIOD. After five days of treatment, his pain improved, but he developed persistent fever and shortness of breath. Blood CMV levels rose to 1.64 × 105 copies/ml after one month of ganciclovir treatment. Significant bone marrow suppression was observed after combined treatment with foscarnet. Anti-rejection treatment was discontinued due to compromised immune function. On day 40, maribavir was initiated with parental consent, resulting in undetectable CMV copies within four days. The patient’s clinical status and bone marrow suppression had improved. Continuing maribavir for two weeks led to the disappearance of CMV viremia, no bone marrow suppression, and normal liver and kidney functions. This case demonstrates the successful short-term use of maribavir in the treatment of refractory CMV infection in an immune-deficient child after renal transplantation. Further studies are required to explore the efficacy and safety of maribavir in pediatric patients.

OsHV-1 Promoter-driven Transgene Expression in Bivalve Cells: An In Vitro Study with an EGFP-tagged Oncogenic H-RasV12.

Bivalves, being extractive species, support sustainable aquaculture and the principles of a circular bioeconomy. Biotechnological interventions can improve bivalve aquaculture productivity. For example, transgene expression facilitates gene function analysis which enables the identification of desirable traits in bivalves for aquaculture. Transgene expression also finds applications in the development of bivalve cell lines that, in turn, support pathology research, eco-toxicology and aquaculture environment quality assessment, and advancing cultivated seafood technology (aligned with sustainability goals). In this study, the efficacy of a synthesized OsHV-1 (ostreid herpesvirus 1) promoter in driving transgene expression across diverse cell culture systems was tested, including primary cell cultures from the bivalve Magallana bilineata. The expression of the oncogenic H-RasV12, tagged with an enhanced green fluorescent protein (EGFP), under the control of the OsHV-1 promoter was also analyzed. The results showed that the OsHV-1 promoter exhibited better activity than the widely used CMV (cytomegalovirus) promoter, highlighting the potential of synthesized promoters for transgene expression in molluscan cells. Furthermore, the study suggests that optimizing gene delivery methods and incorporating multiple oncogenes could enhance molluscan cell transformation, paving the way for developing bivalve cell lines as valuable tools in aquatic biotechnology.

Cytomegalovirus Seroprevalence in Northern Poland in the Population Planning Pregnancy and Pregnant Women

Cytomegalovirus is an enveloped DNA virus. All forms of CMV infection—primary infection, reactivation, and infection with a different strain—may be asymptomatic. The risk of vertical transmission in the periconceptional period is approximately 20%, the risk of primary infection in the first trimester is approximately 30%, and in the third trimester the risk increases to 70%. However, the most severe forms of congenital cytomegaly in newborns are related to infections in the periconceptional period. Offering a vaccine to the seronegative patients planning pregnancy may decrease incidents of congenital cytomegaly in neonates. The authors performed retrospective analysis of seroprevalence of CMV in 909 women who reported for pre-conceptional visits or routine pregnancy follow-ups (2003–2023). In the analyzed group, 577 (63.7%) women were seropositive. No influence related to the women’s age and place of residence was found. Higher seroprevalence was observed in women with children or those working in contact with many people. In the group of 332 seronegative patients, 21 (0.6%) were diagnosed with primary infection during pregnancy. Vaccinating 36.3% of patients planning pregnancy could significantly decrease the risk of primary infection during pregnancy, vertical transmission of CMV, and symptomatic infection in the neonates.

Clinical characteristics, and outcomes of severe neonatal thrombocytopenia: a retrospective cohort study in China

BackgroundSevere neonatal thrombocytopenia, as a rare but life-threatening disease with multiple etiologies, has limited relevant reports in China. The single-center study was performed in a severe thrombocytopenic cohort to improve the prognosis of this disease.MethodsWe included all the patients diagnosed with severe thrombocytopenia (platelet counts ≤ 50 × 103/µL) in our institution between October 2016 and February 2021, and retrospectively reviewed their electronic records. Comparisons were made according to etiology and outcome.ResultsAmong the 5819 inpatients, 194 with severe thrombocytopenia were included in this study, with 64.4% of the cases manifesting thrombocytopenia within 72 h of life. The highest incidence was recorded among extremely low birth weight neonates (6.5%). The main etiologies included sepsis (22.2%), genetic syndromes (14.4%), perinatal asphyxia (9.8%), necrotizing enterocolitis (NEC; 8.8%), and cytomegalovirus infection (6.7%). The median platelet nadir was 5.0 × 103/µL [IQR:2.0 × 103/µL-16.0 × 103/µL], and 112 patients developed very severe thrombocytopenia (platelet counts ≤ 30 × 103/µL), of which 21.4% were associated with late-onset sepsis. In 45 culture-positive cases, the gram-negative group had a lower level of platelets (mean [SD]: 28 [11]×103/µL) as compared to the gram-positive group (mean [SD]: 39 [12]×103/µL). A total of 120 cases (61.9%) exhibited evidence of hemorrhage, with patients diagnosed with NEC demonstrating the highest incidence of hemorrhage at 58.8%. The platelet counts took a median of 10 days to recover: 11 and 7 days for early and late-onset cases; 15 days without and 21 days with platelet transfusions, respectively. The overall mortality rate was 26.8%. The causes of severe thrombocytopenia in 32.7%, 19.2%, and 17.3% of patients who died were identified as sepsis, birth asphyxia, and NEC, respectively. The levels of PT (P = 0.025), APTT (P = 0.046), and lactate (P = 0.028) were lower among surviving patients.ConclusionsSepsis, genetic syndromes, and perinatal asphyxia are the predominant etiologies of severe neonatal thrombocytopenia in China. The overall prognosis of severe neonatal thrombocytopenia is poor, but its severity and outcome were related to laboratory results (PT, APTT, and lactate) and the underlying etiology.

Risk factors for hemorrhagic cystitis in children with severe beta-thalassemia after allogeneic hematopoietic stem cell transplantation

PurposeTo investigate the risk factors for hemorrhagic cystitis (HC) in children with severe beta-thalassemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsThe clinical data of 152 children under the age of 15 who underwent allo-HSCT between January 2011 and December 2021 were retrospectively analyzed. The incidence of HC and related variables were evaluated using univariate analysis. Variables with statistical significance (P &amp;lt; 0.05) were included in a multivariable logistic regression model to identify independent risk factors for HC.ResultsAmong the 152 children, 42 developed HC, with an incidence rate of 27.63%. The median onset time of HC was 25 days (IQR: 10–38.75 days). Univariate analysis indicated that older transplantation age, elevated pre-transplant serum ferritin levels, cytomegalovirus (CMV) infection, and prolonged neutrophil engraftment time were associated with HC occurrence (P &amp;lt; 0.05). Multivariable logistic regression further confirmed that older transplantation age (OR 1.236, 95% CI: 1.031–1.531, P = 0.033), elevated pre-transplant ferritin levels (OR 1.053, 95% CI: 1.028–1.086, P &amp;lt; 0.01), CMV infection (OR 11.522, 95% CI: 2.912–76.345, P = 0.002), and prolonged neutrophil engraftment time (OR 1.385, 95% CI: 1.109–1.793, P &amp;lt; 0.01) were independent risk factors for HC.ConclusionOlder transplantation age (&amp;gt;5.95 age years old), elevated pre-transplant serum ferritin levels, CMV infection, and delayed neutrophil engraftment are independent risk factors for HC in children with severe beta-thalassemia after allo-HSCT. Early identification and intervention for these risk factors are crucial in reducing the incidence of HC.