Estimates of congenital cytomegalovirus-attributable infant mortality in high-income countries: A review.

As many as 5%-10% of infants with symptomatic congenital cytomegalovirus (cCMV) disease, or 0.4%-0.8% of all liveborn infants with cCMV infection, die in early infancy in high-income countries. However, estimates are uncertain due to several potential biases that can result from data limitations and study designs. First, infants with cCMV infections who die prior to diagnosis, which usually occurs at 1-4 weeks after birth, may be excluded from both the count of deaths and the denominator of cCMV births, resulting in left truncation and immortal time biases. These 'biases' are features of the data and do not reflect bias on the part of researchers, but understanding the potential existence of threats to validity can help with interpretation of findings. Left truncation of infant deaths occurring prior to diagnosis of cCMV can result in understatement of the burden of infant deaths due to cCMV. Conversely, overestimation of infant deaths associated with symptomatic cCMV may occur in clinical case series owing to greater representation of relatively severely affected infants owing to ascertainment and referral biases. In this review, we summarise the characteristics of 26 studies that reported estimates of cCMV-associated infant deaths, including potential biases or limitations to which those estimates may have been subject. We discuss study designs whose implementation might generate improved estimates of infant deaths attributable to cCMV. More complete estimates of the overall public health impact of cCMV could inform current and future screening, prevention, and vaccine research.

What are the neurodevelopmental outcomes of children with asymptomatic congenital cytomegalovirus infection at birth? A systematic literature review.

Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5 years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.

Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.

Human microRNA sequencing and cytomegalovirus infection risk after kidney transplantation.

Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.

Performance of eight commercial immunoassays for the detection of cytomegalovirus-specific IgM antibodies in pregnancy - no test fits all needs.

Detection of cytomegalovirus (CMV)-specific immunoglobulin M (IgM) antibodies as first-line serologic diagnosis plays an important role in identifying CMV primary infection during pregnancy. The performance characteristics of eight commercially available CMV IgM assays were compared. Sensitivity and IgM antibody kinetics were assessed using 100 acute phase and follow-up sera from 39 pregnant women with a well-defined onset of CMV primary infection. Specificity was analyzed using 50 well-characterized serum samples from pregnant women not infected or latently infected with CMV and from patients with other acute infections. Until 12 weeks after the onset of primary infection, four assays showed sensitivities of 100%, whereas the others had individual gaps to detect all primary infections in this time period. All assays showed a time-dependent decrease of IgM levels. More than 12 weeks after the onset of infection, the IgM-positive rates varied considerably between tests. The specificity was between 92% and 98% in all but one assay. The observed differences in the performance characteristics must be taken into account in CMV screening and diagnosis of primary infection during pregnancy.

Accuracy of quantitative viral secondary standards: a re-examination.

Interlaboratory agreement of viral load assays depends on the accuracy and uniformity of quantitative calibrators. Previous work demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values in both log10 copies/mL and log10 international unit (IU)/mL, with bias from manufacturer-assigned nominal values of 0.0-0.9 log10 units (either copies or IU)/mL. Standards normalized to IU and those values assigned by dPCR rather than by real-time PCR (qPCR) showed better agreement with nominal values. The latter reinforces prior conclusions regarding the utility of using such methods for quantitative value assignment in reference materials. Quantitative standards have improved over the last several years, and the remaining bias from nominal values might be further reduced by universal implementation of dPCR methods for value assignment, normalized to IU. IMPORTANCE: Interlaboratory agreement of viral load assays depends on accuracy and uniformity of quantitative calibrators. Previous work, published in JCM several years ago, demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values, indicating a substantial improvement in the production of accurate secondary viral standards, while supporting the need for further work in this area and for the broad adaption of international unit (IU) as a reporting standard for quantitative viral load results.

From diagnosis to management: current perspectives on congenital cytomegalovirus infection.

PURPOSE OF REVIEW: Congenital CMV (cCMV) infection is the most common infection of newborns and a leading cause of hearing loss and other neurologic disabilities in children. This review focuses on the diagnosis, presentation and management of cCMV infection. RECENT FINDINGS: Cytomegalovirus is one of the leading causes of sensorineural hearing loss in children. It also leads to neurodevelopmental disabilities and learning problems throughout childhood in both symptomatic and asymptomatic newborns. Urine and saliva PCR testing are the preferred methods of testing newborn infants for cCMV. In recent years, newborn-targeted and universal screening programs have been implemented in several states and major medical centers with the goal of identifying infected infants at risk for hearing loss. Treatment for infants diagnosed with cCMV infection should be limited to those who are moderately to severely symptomatic at birth with cCMV infection, though treatment may be beneficial for children who are asymptomatic with isolated sensorineural hearing loss. SUMMARY: As more children with cCMV are being identified through newborn screening, understanding the clinical presentation and sequelae is important for appropriate management of children with cCMV.

Assessment of blood viral load in asymptomatic and symptomatic cases of congenital cytomegalovirus infection.

This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.

Cytomegalovirus pneumonia with intermittent pulmonary hemorrhage leading to asphyxia death: a case report and literature review.

Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.

A diagnostic dilemma: cytomegalovirus colitis as an uncommon comorbidity in inflammatory bowel disease: a case report.

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.

Neurodevelopmental outcomes of children with congenital cytomegalovirus: a systematic scoping review.

BACKGROUND: With the emergence of newborn congenital cytomegalovirus (cCMV) screening programs, more infants are being diagnosed and require long-term follow-up. The objective of the study was to summarize the literature to date on neurodevelopmental outcomes in children with cCMV with attention to study-specific definitions of disease severity (symptomatic vs. asymptomatic). METHODS: This systematic scoping review included studies of children with cCMV (≤18 years-old) measuring neurodevelopment in ≥1 domain: global, gross motor, fine motor, speech/language, and intellectual/cognitive. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, PsychInfo, and Embase databases were searched. RESULTS: 33 studies met inclusion criteria. Global development most frequently measured (n = 21), followed by cognitive/intellectual (n = 16) and speech/language (n = 8). Most (31/33) studies differentiated children by cCMV severity (symptomatic vs. asymptomatic), definitions of which ranged broadly. 15/21 studies described global development categorically (e.g., normal vs. abnormal). Across studies and domains, children with cCMV generally had equivalent or lower scores (vs. controls or normed measures). CONCLUSIONS: Variation in definitions of cCMV severity and blunt categorical outcomes may limit the generalizability of findings. Future studies should utilize standardized definitions of disease severity and in-depth measurement and reporting of neurodevelopmental outcomes in children with cCMV. IMPACT: Neurodevelopmental delays are common among children with cCMV, although gaps in the literature to have made quantification of such delays challenging. Variation in definitions of asymptomatic and symptomatic cCMV as well as the use of categorical outcomes of neurodevelopment (e.g., normal vs. abnormal) limits the generalizability and clinical utility of findings.

Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection.

Cytomegalovirus is the most common cause of congenital infectious disease and the leading nongenetic etiology of sensorineural hearing loss. Although most infected neonates are asymptomatic at birth, congenital cytomegalovirus infection is responsible for nearly 400 infant deaths annually in the United States and may lead to significant long-term neurodevelopmental impairments in survivors. The resulting financial and social burdens of congenital cytomegalovirus infection have led many medical centers to initiate targeted testing after birth, with a growing advocacy to advance universal newborn screening. While no cures or vaccines are currently available to eliminate or prevent cytomegalovirus infection, much has been learned over the last five years regarding disease pathophysiology and viral replication cycles that may enable the development of innovative diagnostics and therapeutics. This Review will detail our current understanding of congenital cytomegalovirus infection, while focusing our discussion on routine and emerging diagnostics for viral detection, quantification, and long-term prognostication. IMPACT: This review highlights our current understanding of the fetal transmission of human cytomegalovirus. It details clinical signs and physical findings of congenital cytomegalovirus infection. This submission discusses currently available cytomegalovirus diagnostics and introduces emerging platforms that promise improved sensitivity, specificity, limit of detection, viral quantification, detection of genomic antiviral resistance, and infection staging (primary, latency, reactivation, reinfection).

The changing landscape of infections in the lung transplant recipient.

PURPOSE OF REVIEW: Infections in lung transplant recipients remain a major challenge and can affect lung allograft function and cause significant morbidity and mortality. New strategies for the prevention and treatment of infection in lung transplantation have emerged and are reviewed. RECENT FINDINGS: For important vaccine preventable infections (VPIs), guidance has been updated for at risk solid organ transplant (SOT) recipients. However, data on the efficacy of newer vaccines in lung transplant, including the respiratory syncytial virus (RSV) vaccine, are limited. Studies demonstrate improved vaccination rate with Infectious Diseases consultation during pretransplant evaluation. Two new antiviral agents for the treatment and prevention of cytomegalovirus (CMV) in SOT, letermovir and maribavir, are being incorporated into clinical care. CMV-specific cell-mediated immune function assays are more widely available. Antibiotics for the management of multidrug resistant pathogens and Burkholderia cepacia complex have been described in case series and case reports in lung transplant. SUMMARY: Although new vaccines and novel therapies for preventing and treating infections are available, larger studies evaluating efficacy in lung transplant recipients are needed.

Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy.

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements.

Predictors of Cytomegalovirus Recurrence Following Cessation of Posttransplant Prophylaxis.

INTRODUCTION: Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation. CMV prophylaxis is commonly administered in the first year following transplantation to reduce CMV infection; however, the risk factors for long-term reactivation remain unclear. We investigated the timing and risk factors of CMV infection after prophylactic administration. METHODS: This study was a retrospective review of the institutional lung transplantation database from June 2014 to June 2022. Data on patient characteristics, pretransplantation laboratory values, postoperative outcomes, and CMV infection were collected. Donor CMV-IgG-positive and recipient CMV-IgG-negative groups were defined as the CMV mismatch group. RESULTS: During the study period, 257 patients underwent lung transplantation and received a prophylactic dose of valganciclovir hydrochloride for up to 1 y. CMV infection was detected in 69 patients (26.8%): 40 of 203 (19.7%) in the non-CMV mismatch group and 29 of 54 (53.7%) in the CMV mismatch group (P < 0.001). CMV infection after prophylaxis occurred at a median of 425 and 455 d in the CMV mismatch and non-CMV mismatch groups, respectively (P = 0.07). Multivariate logistic regression analysis revealed that preoperative albumin level (odds ratio [OR] = 0.39, P = 0.04), CMV mismatch (OR = 15.7, P < 0.001), and donor age (OR = 1.05, P = 0.009) were significantly associated with CMV infection. CONCLUSIONS: CMV mismatch may have increased the risk of CMV infection after lung transplantation, which decreased after prophylaxis. In addition to CMV mismatch, low preoperative albumin level and donor age were independent predictors of CMV infection.

Safety and efficacy of a reduced frequency viral monitoring strategy for Epstein-Barr virus, cytomegalovirus, and BK polyomavirus post-kidney transplant: A quality assurance initiative.

BACKGROUND: There is variability in recommended viral monitoring protocols after kidney transplant. In response to increased demand for laboratory testing during the COVID-19 pandemic, the Transplant Manitoba Adult Kidney Program updated its monitoring protocols for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) to a reduced frequency. METHODS: This single-center nested case-control study evaluated 252 adult kidney transplant recipients transplanted from 2015 to 2021, with the updated protocols effective on March 19th 2020. Cases included recipients transplanted after the protocol update who developed CMV, EBV, and BKV DNAemia and were matched to controls with DNAemia transplanted prior to the protocol update. The primary outcome was the difference in maximum DNA load titers between cases and matched controls. Secondary outcomes included time to initial DNAemia detection and DNAemia clearance. Safety outcomes of tissue-invasive viral disease were described. RESULTS: There were 216 recipients transplanted preupdate and 36 recipients postupdate. There was no difference between cases and controls in maximum or first DNA load titers for EBV, CMV, or BKV. Cases experienced earlier EBV DNAemia detection (26 (IQR 8, 32) vs. 434 (IQR 96, 1184) days, p = .005). Median follow-up was significantly longer for recipients transplanted preupdate (4.3 vs. 1.3 years, p < .0001). After adjusting for follow-up time, there was no difference in DNAemia clearance or tissue-invasive viral disease. CONCLUSION: Our findings suggest that reduced frequency viral monitoring protocols may be safe and cost-effective. This quality assurance initiative should be extended to detect longer-term and tissue-invasive disease outcomes.

Human cytomegalovirus-related gastrointestinal disease after kidney transplantation: A systematic review.

BACKGROUND: Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID). METHODS: We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs. RESULTS: Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3). CONCLUSIONS: The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.

"Minimally symptomatic" congenital cytomegalovirus infection: latest data and emerging concepts.

PURPOSE OF REVIEW: Universal and targeted screening of newborns for congenital cytomegalovirus (CMV) infection is increasing globally. Questions remain concerning the management of infants who have been identified with congenital CMV infection, especially those with "minimally symptomatic" or clinically inapparent infection. Our objective is to discuss current management of CMV-infected neonates with a focus on less affected infants with or without sensorineural hearing loss (SNHL). RECENT FINDINGS: Valganciclovir is being prescribed increasingly in neonates with congenital CMV infection for improvement in hearing outcomes through 2 years of age. Treatment initiated in the first month of age is recommended for clinically apparent disease. A recent study showed hearing improvement at 18-22 months of age when therapy was initiated at age 1-3 months in infants with clinically inapparent CMV infection and isolated SNHL. SUMMARY: Antiviral therapy with either ganciclovir or valganciclovir has shown moderate benefit in prevention of hearing deterioration among infants with clinically apparent CMV infection or isolated SNHL. Sustainability of benefit beyond 2 years of age remains unknown. At present, infants with clinically inapparent CMV infection (normal complete evaluation including hearing) should not receive antiviral therapy. All CMV-infected infants require close audiological and neurodevelopmental follow-up.

Cytomegalovirus colitis as intestinal obstruction in an immunocompetent adolescent: a case report and literature review.

BACKGROUND: Cytomegalovirus infection manifests varying clinical characteristics and severity in diverse populations with different immune statuses. The signs and symptoms of gastrointestinal involvement are nonspecific. Here, we present a case of cytomegalovirus colitis in an immunocompetent adolescent, which manifested as intestinal pseud-obstruction. CASE PRESENTATION: A 15-year-old man who had contracted novel coronavirus infection one month earlier was admitted to our hospital with fever, abdominal pain, and hematochezia. His abdomen was distended, and laboratory evaluation revealed a decrease in the blood count, an increase in inflammatory indicators and hepatic impairment. Imaging shows bowel wall thickening and dilatation of the colon. A diagnosis of intestinal infection combined with acute intestinal pseud-obstruction was made. Diarrhea persisted despite conservative treatment with empirical antibiotics. A colonoscopy was performed. Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery. CONCLUSIONS: The case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease. Clinical and endoscopic manifestations are typically nonspecific, and imaging shows typical signs of intestinal obstruction. The final diagnosis was confirmed by pathology. Most of them have a good prognosis. We suggest that cytomegalovirus colitis can also lead to intestinal obstruction and that viral reactivation in immunocompetent individuals may be associated with inflammatory conditions and viral coinfection, particularly with the novel coronavirus.

An adult with hemorrhagic varicella co-infects with cytomegalovirus: a case report.

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.