Cytomegalovirus Testing Research Articles

Testing for genetic and viral etiologies in congenital hearing loss based on a survey of cochlear implant centers: proposed HEARRING group consensus and future directions

Background In cases of congenital sensorineural hearing loss, testing for genetic etiologies and congenital cytomegalovirus (cCMV) infection have become common practice. Aims/Objectives The purpose of this study is to determine which specific testing methodologies should be used and when. Material and methods We surveyed 20 practicing otolaryngologists across eighteen institutions in thirteen countries about their approach to cCMV, GJB2, and wider genetic testing. Results We found 90% of respondents employ all three tests, either in routine or special cases. cCMV testing is widely used, with 95% of respondents incorporating it into their clinical practice. GJB2 testing was employed by 90%. In cases with negative GJB2 test results, a majority of respondents proceeded to wider genetic screening. Test reimbursement was also examined for each test. For cCMV testing, 63.1% reported reimbursement, 68.4% reported reimbursement for GJB2 variant testing and 52.6% reported reimbursement for wider genetic screening. Conclusions and significance A common approach is to perform cCMV and GJB2 testing as the first tests, followed by wider genetic testing. This study offers insight into the prevalence, methodologies, and reimbursement status of these testing methodologies across multiple hearing centers and countries. Current consensus and future directions are described based on the current survey.

Diffusion Tensor Imaging of the Auditory Pathway in Prelingual Deaf Children in Comparison to Normal Hearing Children in the 1 to 7 Years of Age Group

Abstract Objective This article aims to determine the microstructural alterations in the auditory pathway in prelingual deaf children using diffusion tensor imaging (DTI)-derived parameters—fractional anisotropy (FA) and apparent diffusion coefficient (ADC), and secondarily to evaluate these changes in rubella and cytomegalovirus (CMV) positive cases. Method A consecutive series of consenting deaf and normal children between 1 and 7 years of age, forming the case and control groups, respectively, underwent DTI, audiological tests, and testing for rubella, CMV, and toxoplasma infections. FA and ADC were measured at four locations bilaterally: lateral lemniscus (LL), inferior colliculus, medial geniculate body, and auditory cortex (AC). Result The mean ADC values were higher and the mean FA values were lower in cases (19 males, 21 females, mean age 2.65 years) than the controls (21 males, 19 females, mean age 4.63 years) at all eight sites. Sixteen (40%), 17 (42.5%), and 7 (17.5%) cases had severe, severe to profound, and profound hearing loss, respectively, the FA and ADC values being significantly different for LL. For rubella and CMV immunoglobulin G, 20/40and 17/40 cases were positive, respectively, 11 for both, and none for toxoplasma. Significant decrease in FA was seen at LL and AC in rubella/CMV positive cases. Conclusion Microstructural changes are seen throughout the auditory pathway in prelingual deaf children, especially with rubella and/or CMV positive status. Further studies may pave the path to segregate out patient groups potentially more responsive to cochlear implant.

Congenital Cytomegalovirus Infection: Update on Screening, Diagnosis and Treatment: Scientific Impact Paper No. 56.

Cytomegalovirus (CMV) is the most common cause of viral infection in newborn babies, and affects 1 in 200 of all live born infants in high-income countries; and 1 in 71 in low- and middle-income countries. It is a major cause of hearing loss and brain damage. Women may get CMV infection for the first time during pregnancy (primary infection) or may experience 'non-primary' infection, either by reactivation of previous CMV infection or by a new infection with a different strain of the virus. The most common source of infection to pregnant women is the saliva and urine of young children. Therefore, all pregnant women, especially those in regular contact with young children, should be informed about hygiene-based measures to reduce the risks, e.g. handwashing. The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV. Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection. The risk of harm to the fetus is greatest following primary CMV infection of the woman in early pregnancy, and appears to be very low following infection after 12 weeks of pregnancy. Babies with CMV infection at birth may have jaundice, a rash, enlarged liver or spleen, a small brain, or be small for their gestational age. Around 1 in 8 babies born with CMV infection will have clinically detectable signs at birth. The rest will not have any features detectable by clinical examination alone. Therefore, all infants with CMV infection at birth should be followed up at a minimum of up to 2 years of age or later, depending upon the disease status, to check hearing and brain development. Following primary CMV infection in the first 12 weeks of pregnancy, if the woman starts taking the antiviral medicine valaciclovir (valacyclovir) it reduces the risk of the baby becoming infected. Where CMV infection of the fetus in the womb has been confirmed (by amniocentesis, for example), regular ultrasound scans should be offered every 2-3 weeks until birth. Detailed assessment of the fetal brain is an essential part of these scans. Where maternal CMV infection occurs, but fetal infection is not confirmed, repeated ultrasound scans of the fetus should be offered every 2-3 weeks until birth. In infected fetuses, as well as ultrasound scans, an MRI scan of the brain should be offered at 28-32 weeks of gestation (and sometimes repeated 3-4 weeks later) to assess for any signs of harm to the fetal brain. All babies born to women with confirmed or suspected CMV infection should be tested for CMV with a urine or saliva sample within the first 21 days of life. In newborns with symptomatic CMV infection at birth, treatment with antiviral medicine (valganciclovir or ganciclovir) can reduce hearing loss in 5 out of 6 babies, and improve long-term brain development outcomes in some. There is no licensed vaccine for CMV.

The Utility of Serologic TORCH Testing During Pregnancy for Maternal-related Versus Fetal-related Indications: A Retrospective Study.

Clear guidelines have not been established about the utility of TORCH serology testing in women for whom TORCH infection is suspected according to clinical and laboratory manifestations during pregnancy. We aimed to compare rates of TORCH infections [specifically cytomegalovirus (CMV), Toxoplasma and rubella] in women who underwent TORCH serology testing due to maternal- versus fetal-related indications. This 10-year single-center retrospective study included all the women beyond 24 weeks of gestation who underwent TORCH serology testing due to maternal- or fetal-related indications. Maternal-related indications included fever, gastroenteritis, elevated liver enzymes and thrombocytopenia. Fetal-related indications included intrauterine growth restriction, polyhydramnios and oligohydramnios. During the study period, 304 women underwent TORCH serology testing due to maternal-related indications and 771 due to fetal-related indications. For the maternal-related compared with the fetal-related indication group, maternal and congenital TORCH infections were more prevalent (P = 0.015), specifically CMV (P = 0.036). Eight (2.6%) of the women with maternal-related indications had a primary TORCH infection; 4 of them (50%) had concomitant congenital infections. Six (0.8%) of the women with fetal-related indications had a primary infection; none had a related congenital infection. Among the women with maternal-related indications, higher rates of maternal TORCH infection were found among those with thrombocytopenia (7.1%) and elevated liver enzymes (3.0%). During the study period, maternal-indicated TORCH testing detected 10.8% of neonates born with a confirmed TORCH infection. The clinical yield of TORCH serology for nonspecific sonographic fetal features was low. Nonetheless, maternal-related indications should prompt testing for CMV and Toxoplasma infection.

Maternal Cytomegalovirus (CMV) Serology: The Diagnostic Limitations of CMV IgM and IgG Avidity in Detecting Congenital CMV Infection.

Congenital cytomegalovirus (cCMV) is a common congenital viral infection. Testing for cCMV usually begins with assessing maternal CMV serology, specifically IgM and IgG antibodies. A negative maternal CMV IgM suggests a low risk of recent maternal CMV infection, thereby suggesting a low risk of cCMV in the fetus. Consequently, cCMV is often ruled out when maternal CMV IgM is negative. In our perinatal autopsy and placental pathology database, we identified 5 cases of cCMV despite negative maternal CMV IgM results in the second trimester. In all 5 cases, fetal abnormalities were first detected by ultrasound in the second trimester, prompting maternal CMV testing. Since second trimester maternal CMV IgM was negative in all cases, cCMV was considered unlikely, thus precluding further prenatal CMV testing in 4 of these cases. The diagnosis of cCMV was subsequently made through placental and/or autopsy examinations. Following this diagnosis, retrospective CMV serology and IgG avidity testing was performed on stored frozen first-trimester maternal blood samples in 3 cases. Among these, the first-trimester samples in 2 cases were IgG+, IgM+, and exhibited low IgG avidity, suggesting a primary maternal CMV infection around the time of conception. In the third case, both first and second-trimester maternal blood samples were IgG+, IgM-, and showed high IgG avidity, suggesting a non-primary maternal CMV infection (i.e., reactivation or reinfection of CMV). A negative maternal CMV IgM in the second trimester cannot exclude cCMV infection. While CMV IgG avidity testing and analysis of stored frozen first-trimester maternal blood samples provide valuable insights, they have limitations. CMV PCR performed on amniotic fluid is a useful prenatal diagnostic tool. For cases of unexplained fetal abnormalities or death, autopsy and placental examination are recommended.

Concordance of Cytomegalovirus Saliva and Urine Testing in Infants for the Detection of Congenital Infection.

Congenital cytomegalovirus is a leading cause of neurodevelopmental impairment and sensorineural hearing loss. We evaluated infants ≤21 days postnatal age who had both urine and saliva cytomegalovirus testing and determined concordance between the 2 tests and influence of very low birth weight on concordance. Discordance was low overall between urine and saliva testing; however, discordance was high in very low birth weight infants.

The association between cytomegalovirus infection and neurodegenerative diseases: a prospective cohort using UK Biobank data

Certain viral infections have been linked to the development of neurodegenerative diseases. This study aimed to investigate the association between cytomegalovirus (CMV) infection and five neurodegenerative diseases, spinal muscular atrophy (SMA) and related syndromes, Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and disorders of the autonomic nervous system (DANS). This prospective cohort included white British individuals who underwent CMV testing in the UK Biobank from January 1, 2006 to December 31, 2021. A Cox proportional hazard model was utilized to estimate the future risk of developing five neurodegenerative diseases in individuals with or without CMV infection, adjusted for batch effect, age, sex, and Townsend deprivation index in Model 1, and additionally for type 2 diabetes, cancer, osteoporosis, vitamin D, monocyte count and leukocyte count in Model 2. Bidirectional Mendelian randomization was employed to validate the potential causal relationship between CMV infection and PD. A total of 8346 individuals, consisting of 4620 females (55.4%) and 3726 males (44.6%) who were white British at an average age of 56.74 (8.11), were included in this study. The results showed that CMV infection did not affect the risk of developing AD (model 1: HR [95% CI]=1.01 [0.57, 1.81], P=0.965; model 2: HR=1.00 [0.56, 1.79], P=0.999), SMA and related syndromes (model 1: HR=3.57 [0.64, 19.80], P=0.146; model 2: HR=3.52 [0.63, 19.61], P=0.152), MS (model 1: HR=1.16 [0.45, 2.97], P=0.756; model 2: HR=1.16 [0.45, 2.97], P=0.761) and DANS (model 1: HR=0.65 [0.16, 2.66], P=0.552; model 2: HR=0.65 [0.16, 2.64], P=0.543). Interestingly, it was found that participants who were CMV seronegative had a higher risk of developing PD compared to those who were seropositive (model 1: HR=2.37 [1.25, 4.51], P=0.009; model 2: HR=2.39 [1.25, 4.54], P=0.008) after excluding deceased individuals. This association was notably stronger in males (model 1: HR=3.16 [1.42, 7.07], P=0.005; model 2: HR=3.41 [1.50, 7.71], P=0.003), but no significant difference was observed in the female subgroup (model 1: HR=1.28 [0.40, 4.07], P=0.679; model 2: HR=1.27 [0.40, 4.06], P=0.684). However, a bidirectional Mendelian randomization analysis did not find a genetic association between CMV infection and PD. The study found that males who did not have a CMV infection were at a higher risk of developing PD. The findings provided a new viewpoint on the risk factors for PD and may potentially influence public health approaches for the disease. National Natural Science Foundation of China (81873776), Natural Science Foundation of Guangdong Province, China (2021A1515011681, 2023A1515010495).

Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan. The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Hematopoietic stem cell transplantation patients who received letermovir between May 2018 and May 2022 were registered. Data collected included physician-assessed adverse events/adverse drug reactions and clinical effectiveness (development of CMV disease, CMV antigen status, and use of preemptive therapy). A total of 821 HSCT patients were included in the safety analyses. Adverse drug reactions occurred in 11.33% of patients, with serious adverse drug reactions in 3.05%. The five most common adverse drug reactions were nausea (1.58%), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). A total of 670 patients were eligible for effectiveness analyses. Among these patients, 16.57% and 28.66% required preemptive therapy through week 14 and week 48, respectively. In addition, relatively few patients developed CMV disease throughout the follow-up period (1.34% at week 14 and 3.85% at week 48). This final analysis of post-marketing surveillance with up to 48 weeks follow-up period in Japan provides further evidence supporting the safety profile and effectiveness of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

Managing recurrent parvovirus B19-associated anemia after a pediatric kidney transplant

A 13-year-old girl who had a kidney transplant four weeks prior presented with a 10-day history of fatigue, paleness, and headache. On physical examination, tachycardia and paleness were noted. Laboratory testing was notable for severe anemia and mild leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) test for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative and for parvovirus B19 (PVB19) was positive. Despite lower immunosuppression and administration of intravenous immunoglobulin (IVIG) it persisted for 15 months, and frequent red blood cell transfusions were needed. PVB19 is a less common but significant complication. The patient's clinical course demonstrates the importance of this complication and the challenges in its management. A notable void exists in the literature regarding standardized treatment protocols for PVB19-induced recurrent anemia after kidney transplant. This case indicates the need for further research and consensus to guide effective clinical interventions in similar cases.

Congenital Cytomegalovirus Testing Outcomes From the ValEAR Trial.

To determine the positivity rate of congenital cytomegalovirus (cCMV) testing among universal, hearing-targeted CMV testing (HT-cCMV) and delayed targeted dried blood spot (DBS) testingnewborn screening programs, and to examine the characteristics of successful HT-cCMV testing programs. Prospective survey of birth hospitals performing early CMV testing. Multiple institutions. Birth hospitals participating in the National Institutes of Health ValEAR clinical trial were surveyed to determine the rates of cCMV positivity associated with 3 different testing approaches: universal testing, HT-cCMV, and DBS testing. A mixed methods model was created to determine associations between successful HT-cCMV screening and specific screening protocols. Eighty-two birth hospitals were surveyed from February 2019 to December 2021. Seven thousand six hundred seventy infants underwent universal screening, 9017 infants HT-cCMV and 535 infants delayed DBS testing. The rates of cCMV positivity were 0.5%, 1.5%, and 7.3%, respectively. The positivity rate for universal CMV screening was less during the COVID-19 pandemic than that reported prior to the pandemic. There were no statistically significant drops in positivity for any approach during the pandemic. For HT-cCMV testing, unique order sets and rigorous posttesting protocols were associated with successful screening programs. Rates of cCMV positivity differed among the 3 approaches. The rates are comparable to cohort studies reported in the literature. Universal CMV prevalence decreased during the pandemic but not significantly. Institutions with specific order set for CMV testing where the primary care physician orders the test and the nurse facilitates the testing process exhibited higher rates of HT-cCMV testing.

дилатационной кардиомиопатией Клинический случай медицинской реабилитации пациента с дилатационной кардиомиопатией

The paper provides a clinical case of physical and medical rehabilitation of patient D born in 1963. Principal diagnosis established in 2018 according to ICD-10: I42.0 dilated cardiomyopathy. Laboratory testing revealed DNA of herpes virus 6 (HHV6), positive test for cytomegalovirus (CMV) DNA, 6.0×102 copies/mL, positive test for the Epstein–Barr virus (EBV) DNA, 7.2×103 copies/mL. In April 2018, the patient underwent successful surgery, implantation of the biventricular bypass system supplemented by membrane oxygenation. Physical rehabilitation was performed that yielded positive results.

Fetal Cytomegalovirus Infection in the Absence of Maternal Cytomegalovirus-IgM Seropositivity

The aim of this study was to evaluate maternal serological status and fetal sonographic findings of Cytomegalovirus (CMV) infection. This is a retrospective study performed at Perinatology Department of Istanbul Başakşehir Çam and Sakura City Hospital. A computerized search was conducted to identify cases who underwent prenatal diagnosis of fetal CMV infection between September 2020 and December 2023. We identified nine cases with fetal CMV infection. The clinical data of the patients, gestational age at the time of diagnosis, serological, sonographic findings, and pregnancy outcomes were analyzed. A computer search of the database was made for the seroprevalance of CMV-IgM and CMV-IgG in our population. The CMV-IgM and IgG results of the 1235 patients who underwent CMV screening in the first trimester between September 2020 and December 2023 were evaluated. Fetal CMV infection was identified in nine patients. None of the 9 cases showed maternal CMV-IgM positivity. Seven of the 9 patients showed high IgG avidity index. Pregnant population had 98 % positivity for CMV-IgG. The evaluation of serologic tests for CMV is not straightforward in the second and third trimester. IgM and IgG avidity should be interpreted with caution in the second and third trimester. In the presence of ultrasound findings suggesting fetal CMV infection and CMV-IgG positivity, invasive diagnostic tests rather than serological test should be discussed with the patient, and non-primary infections should always be considered to minimize overlooked fetal cytomegalovirus infections and missed antiviral treatment opportunity.

Pregnancy assistance for foreign women in Trentino Region (Northern Italy): retrospective cohort epidemiological study.

to identify any differences between Italian and foreign women in the access to prenatal care, including the number and appropriate scheduling of visits, the execution of diagnostic, blood, and microbiological tests and the use of specific healthcare services. retrospective cohort epidemiological study, based on the monitoring of current information flows. data extrapolated from the Birth Attendance Certificate information flow of the Autonomous Province of Trento (Northern Italy) between 2012 and 2016. A total of 23,165 women with data regarding citizenship were included in the analysis. outcome variables used to assess appropriateness of antenatal care were medically assisted procreation techniques, use of invasive prenatal diagnosis, gestational age at the first appointment, total number of appointments and ultrasounds during pregnancy, blood and microbiological tests taken, and participation in antenatal classes. data indicates a significant difference in the use of chorionic villus sampling, testing for Cytomegalovirus, and vaginal-rectal swab for the detection of group B streptococcus, which are lower in the foreign population. Furthermore, there is a statistically significant difference in the gestational age at which the first appointment is attended, in the total number of visits, and in the number of ultrasounds performed during pregnancy as well as in participation in antenatal classes. this study reveals significant differences in access and use of pregnancy assistance between foreign and Italian women. There are also differences in terms of social determinants of health, with a concentration of unemployment and low education in the foreign population. It is therefore necessary to identify the factors that can potentially create health inequalities, considering the socioeconomic determinants and the specific needs of migrant women.

Viral load kinetics and the clinical consequences of cytomegalovirus in kidney transplantation.

Despite advances in clinical management, cytomegalovirus (CMV) infection remains a serious complication and an important cause of morbidity and mortality following kidney transplantation. Here, we explore the importance of viral load kinetics as predictors of risk and potential guides to therapy to reduce transplant failure in a large longitudinal Genome Canada Transplant Consortium (GCTC) kidney transplant cohort. We examined the relationship between CMV infection rates and clinical characteristics, CMV viral load kinetics, and graft and patient outcomes in 2510 sequential kidney transplant recipients in the British Columbia Transplant Program. Transplants were performed between January 1, 2008, and December 31, 2018, were managed according to a standard protocol, and were followed until December 31, 2019, representing over 3.4 million days of care. Longitudinal CMV testing was performed in 2464 patients, of whom 434 (17.6%) developed a first episode of CMV viremia at a median of 120 (range: 9-3906) days post-transplant. Of these patients, 93 (21.4%) had CMV viremia only and 341 (78.6%) had CMV viremia with clinical complications, of whom 21 (4.8%) had resulting hospitalization. A total of 279 (11.3%) patients died and 177 (7.2%) patients lost their graft during the 12 years of follow-up. Patients with CMV infection were at significantly greater risk of graft loss (p=0.0041) and death (p=0.0056) than those without. Peak viral load ranged from 2.9 to 7.0 (median: 3.5) log10 IU/mL, the duration of viremia from 2 to 100 (15) days, and the viral load area under the curve from 9.4 to 579.8 (59.7) log10 IU/mL × days. All three parameters were closely inter-related and were significantly increased in patients with more severe clinical disease or with graft loss (p=0.001). Duration of the first CMV viremic episode greater than 15 days or a peak viral load ≥4.0 log10 IU/mL offered simple predictors of clinical risk with a 3-fold risk of transplant failure. Viral load kinetics are closely related to CMV severity and to graft loss following kidney transplantation and provide a simple index of risk which may be valuable in guiding trials and treatment to prevent transplant failure.

Establishment of the Norwegian hearing register for children.

The Norwegian Directorate of Health approved the Norwegian Hearing Register for Children in 2022. The main objective of the register is to improve the quality of treatment for children with permanent hearing loss, by measures, follow-ups and monitoring the quality and results of the health care system. Inclusion criteria are children who do not pass universal newborn hearing screening and/or children with permanent hearing loss <18 years of age. Hearing loss is defined as pure-tone audiometry threshold of (PTA4) > 20 dB in at least one ear. Data are registered at the Ear, Nose and Throat departments at inclusion and at follow-ups at the age of 3, 6, 10, and 15 years. The register collects information about the child within a holistic perspective. The key elements of the register are (a) data concerning newborn hearing screening; (b) data concerning hearing, medical information, hearing amplification and intervention (c) patient reported outcome measures registered by caregivers using three questionnaires; Pediatric Quality of Life Inventory, Strengths and Difficulties Questionnaire and Parents' Evaluation of Aural/Oral Performance of Children. The register has established four quality indicators regarding newborn hearing screening and early intervention (a) the rate of false positive neonatal screens; (b) testing for congenital cytomegalovirus within 3 weeks of age for children who do not pass newborn hearing screening; (c) audiological evaluation to confirm the hearing status no later than 3 months of age and (d) initiated intervention within 3 months after confirmation of hearing status. The register will include the total population of hearing impaired children over long time periods. Thus, the register enables each hospital to monitor their quality indicator scores continuously and compare them with national levels in real time. This facilitates and accelerates identification of improvement areas in the hospitals and will be an important contributor for quality improvement in NHS, diagnostics and hearing intervention for children in Norway. In addition, data from the register will be a unique source for research, and study designs with a long follow-up time can be applied.

968. Universal Newborn Testing for Congenital Cytomegalovirus (cCMV) Infection Comes of Age: Clinical Sensitivity of Screening Tests and Infant Outcomes in a cCMV Screening Study in Minnesota

Abstract Background Universal congenital cytomegalovirus (cCMV) screening is controversial. In 2023, we completed a study evaluating analytical and clinical sensitivity of dried blood spots (DBS) for detection of cCMV infection and disease. Analytical sensitivity is the ability of an assay to detect infection, while clinical sensitivity is an assay's ability to identify individuals with disease. The completion of this study coincided with implementation of new legislation making Minnesota the first state in the USA to mandate universal cCMV testing. Methods In six newborn nurseries in Minnesota, consented newborns were screened for cCMV, comparing PCR of saliva with PCR of the DBS obtained for routine newborn screening. Screen-positive infants had a confirmatory urine PCR, and a diagnostic clinical evaluation. Using international consensus criteria, we categorized cCMV cases as: moderate-to-severe; mildly symptomatic; asymptomatic with isolated sensorineural hearing loss (SNHL); or asymptomatic. Results From February 2016 - January 2023, among 23,644 newborns screened, 87 (3.7 per 1,000) were identified with cCMV. Analytical sensitivity of saliva was 93.1% (81); for DBS, it was 73.6% (64) by the UMN lab, and 77.0% (67) by the CDC lab. At birth, 67 (77%) infants were asymptomatic; 6 moderately-to-severely symptomatic (2 with SNHL); 10 mildly symptomatic; and 4 asymptomatic with isolated SNHL. 4 infants had delayed-onset SNHL (2 asymptomatic, 2 symptomatic). Among 20 infants with symptomatic cCMV at birth and/or SNHL, clinical sensitivity of saliva was 95% (19), and for DBS was 75% (15) in the UMN lab, and 85% (17) in the CDC lab. Conclusion This unselected screening study demonstrated a prevalence of 3.7/1000 of cCMV in Minnesota newborns. The enhancement in clinical sensitivity of DBS (over analytical sensitivity) to identify children with symptoms or sequelae suggests their usefulness for cCMV screening, though most identified infants will be asymptomatic. In parallel with this work, in the spring of 2023, Minnesota became the first state to screen all newborns for cCMV, using the newborn DBS. Continued evaluation of CMV DBS testing methods for reproducibility, efficiency, high-throughput capability and clinical correlation will be important as other states consider universal cCMV screening. Disclosures All Authors: No reported disclosures

2730. Clinically significant cytomegalovirus infection in patients with lymphoma and no prior cellular therapy

Abstract Background Reactivation of cytomegalovirus (CMV) is commonly reported in lymphoma patients who undergo cellular therapy, with often poor outcomes. The risk for CMV reactivation in patients with lymphoma prior to cellular therapy is not well understood. As new alternative immunosuppressive therapies emerge for lymphoma, understanding baseline risk for CMV reactivation is paramount to improve clinical and oncologic outcomes. Our goal was to identify risk factors, and describe outcomes associated with clinically significant CMV infection (CS-CMVi) in lymphoma patients with no prior cellular therapy. Methods We performed a retrospective cohort study for all lymphoma patients who underwent testing for CMV by PCR from blood between 1/2017 and 12/2020. Patients with prior history of transplantation or chimeric antigen receptor therapy were excluded. Patients with and without CS-CMVi were identified for risk factor analysis by univariate analysis. Results A total of 217 lymphoma patients were included in our analysis; CS-CMVi was identified in 41 (19%) patients. When compared to patients without CS-CMVi (control group), lymphoma patients with CS-CMVi were more likely to have history of HIV (5% vs 0%; p= 0.0350), primary central nervous system lymphoma (7% vs 1%; p= 0.0220) and relapsed disease (54% vs 25%; p= 0.0005) (Table 1). CS-CMVi was also more common if testing was done at time of relapse diagnosis (32% vs 10%; p= 0.0007), during work up for infection (98% vs 68%; p &amp;lt; 0.0001) and more often (3 vs 1; p &amp;lt; 0.0001) (table 1). Mortality and remission rates within 1 year of testing were worse in patients with CS-CMVi (table 2 and figure 1). Conclusion CS-CMVi in lymphoma patients is associated with poor outcomes including oncologic outcomes. Further analysis to better define patients with lymphoma at high-risk for CS-CMVi should be studied for future preventative strategies. Disclosures Fareed Khawaja, MBBS, MEDSCAPE: Honoraria|Viracor: Grant/Research Support Roy F. Chemaly, MD/MPH, Eurofins-VViracor: Grant/Research Support|Karius: Advisor/Consultant

891. Cytomegalovirus Testing Rates Among Immunocompromised Adults, Adolescents, And Children In The United States

Abstract Background Cytomegalovirus (CMV) is a latent virus that can cause morbidity and mortality among immunocompromised (IC) individuals. No studies have examined how CMV testing changed throughout the COVID-19 pandemic among IC individuals in the United States (US). This study aimed to estimate CMV testing rates among IC adults (18-94 years), adolescents (12-17 years), and children (0-11 years) during the COVID-19 pandemic. Methods This observational cohort study included insured individuals from the US and was conducted using administrative medical and pharmacy claims from HealthVerity from December 2017-May 2022. IC adults, adolescents, and children entered the cohort after 6 months of continuous enrollment and were followed until disenrollment or end of study period. CMV testing was captured using CPT codes (serology and PCR) and was limited to no more than 1 test per day with ≥6 days required between tests. The rate of CMV testing (per 100,000 person-months) was estimated over three time periods defined by key points in the COVID-19 pandemic: pre-COVID-19-era, 06/01/2018-03/31/2020; pre-vaccine-COVID-19-era, 04/01/2020-12/31/2020; and vaccine-COVID-19-era, 01/01/2021-05/31/2022. Results The sample included 735,251 IC adults, of whom 4.8% (N=35,391) had ≥1 CMV test over follow-up (median follow-up, 566 days); 12,203 IC adolescents, of whom 15.5% (N=1,896) had ≥1 CMV test over follow-up (median follow-up, 582 days); and 15,854 IC children, of whom 14.7% (N=2,324) had ≥1 CMV test over follow-up (median follow-up, 702 days). The mean rate of CMV tests per 100,000 person-months for IC adults was 1,660 in the pre-COVID-19-era, 1,040 in the pre-vaccine-COVID-19-era, and 983 in the vaccine-COVID-19-era. Similarly, rates of CMV testing declined among IC adolescents and children (adolescents: 7,391 in pre-COVID-19-era, 4,717 in pre-vaccine-COVID-19-era, and 4,219 in vaccine-COVID-19-era; children: 7,556 in pre-COVID-19-era, 4,467 in pre-vaccine-COVID-19-era, and 4,026 in vaccine-COVID-19-era). The highest testing rates were among those with a history of stem cell transplantation in all age cohorts. Conclusion CMV test utilization decreased during the COVID-19 pandemic era in the US and remained low through the early COVID-19 vaccine era. Disclosures Sandeep Basnet, MD, Moderna Therapeutics: Stocks/Bonds Brent Arakaki, BS, Aetion, Inc.: Employee Katherine E. Mues, PhD, Aetion, Inc.: Employee John D. Diaz-Decaro, PhD, MS, Moderna Therapeutics: Stocks/Bonds

Testing for Cytomegalovirus Among Individuals Who Were Immunocompromised, 2018-2022

This cohort study investigates rates of cytomegalovirus testing before and during the COVID-19 pandemic among individuals who were immunocompromised.

Cytomegalovirus (CMV) Reactivation and CMV-Specific Cell-Mediated Immunity After Chimeric Antigen Receptor T-Cell Therapy.

The epidemiology of cytomegalovirus (CMV) after chimeric antigen receptor-modified T-cell immunotherapy (CARTx) is poorly understood owing to a lack of routine surveillance. We prospectively enrolled 72 adult CMV-seropositive CD19-, CD20-, or BCMA-targeted CARTx recipients and tested plasma samples for CMV before and weekly up to 12 weeks after CARTx. We assessed CMV-specific cell-mediated immunity (CMV-CMI) before and 2 and 4 weeks after CARTx, using an interferon γ release assay to quantify T-cell responses to IE-1 and pp65. We tested pre-CARTx samples to calculate a risk score for cytopenias and infection (CAR-HEMATOTOX). We used Cox regression to evaluate CMV risk factors and evaluated the predictive performance of CMV-CMI for CMV reactivation in receiver operator characteristic curves. CMV was detected in 1 patient (1.4%) before and in 18 (25%) after CARTx, for a cumulative incidence of 27% (95% confidence interval, 16.8-38.2). The median CMV viral load (interquartile range) was 127 (interquartile range, 61-276) IU/mL, with no end-organ disease observed; 5 patients received preemptive therapy based on clinical results. CMV-CMI values reached a nadir 2 weeks after infusion and recovered to baseline levels by week 4. In adjusted models, BCMA-CARTx (vs CD19/CD20) and corticosteroid use for >3 days were significantly associated with CMV reactivation, and possible associations were detected for lower week 2 CMV-CMI and more prior antitumor regimens. The cumulative incidence of CMV reactivation almost doubled when stratified by BCMA-CARTx target and use of corticosteroids for >3 days (46% and 49%, respectively). CMV testing could be considered between 2 and 6 weeks in high-risk CARTx recipients.