Effects Of Cytomegalovirus Infection Research Articles

Effect of cytomegalovirus infection on post-transplant hospitalization days among children undergoing allogeneic hematopoietic cell transplantation: A marginal structural model approach.

Cytomegalovirus (CMV) commonly reactivates after allogeneic hematopoietic cell transplant (HCT), potentially leading to CMV disease and significant morbidity and mortality. To reduce morbidity and mortality, many centers conduct weekly CMV blood polymerase chain reaction (PCR) surveillance testing with subsequent initiation of antiviral therapy upon CMV DNAemia detection. However, the impact of CMV DNAemia on subsequent hospitalization risk has not been assessed using models accounting for the time-varying nature of the exposure, outcome, and confounders. All allogeneic HCTs at the Children's Hospital of Philadelphia from January 2004-April 2017 were considered for inclusion. Patients were monitored with CMV surveillance via PCR testing for up to 105 days after HCT receipt. We estimated the association between CMV DNAemia and rate of hospitalization using marginal structural models (MSM). There were 343 allogeneic HCT episodes in 330 with CMV surveillance; median age was 9.0 (range: 0.1-26.2) and 46.5% were female. And 24.1% of HCT patients had at least one positive CMV blood PCR during the follow-up period. Median time to CMV DNAemia detection was 19 days (range: 4-97). The MSM estimated the incidence rate ratios for an association of CMV DNAemia with hospitalization to be 1.24, (95% confidence interval: 1.04-1.47). CMV DNAemia was associated with an increased hospitalization in the post-HCT period. The MSM accounted for time-varying nature of the outcome, exposure and confounders. The findings support prevention of CMV DNAemia in this population. We recommend further investigation into the effectiveness and safety of prophylaxis versus pre-emptive CMV prevention approaches.

Long-term CMV monitoring and chronic rejection in renal transplant recipients.

Cytomegalovirus (CMV) is well established to be an independent risk factor for graft loss after kidney transplantation (KTx). Monitoring for CMV in the chronic phase is not defined in the current guideline. The effects of CMV infection, including asymptomatic CMV viremia, in the chronic phase are unclear. We performed a single-center retrospective study to investigate incidence of CMV infection in the chronic phase, defined as more than 1 year after KTx. We included 205 patients who received KTx between April 2004 and December 2017. The CMV pp65 antigenemia assays to detect CMV viremia were continuously performed every 1-3 months. The median duration of the follow-up was 80.6 (13.1-172.1) months. Asymptomatic CMV infection and CMV disease were observed in 30.7% and 2.9% in the chronic phase, respectively. We found that 10-20% of patients had CMV infections in each year after KTx which did not change over 10 years. The history of CMV infection in the early phase (within 1 year after KTx) and chronic rejection were significantly associated with CMV viremia in the chronic phase. CMV viremia in the chronic phase was significantly associated with graft loss. This is the first study to examine the incidence of CMV viremia for 10 years post KTx. Preventing latent CMV infection may decrease chronic rejection and graft loss after KTx.

Risk factors of cytomegalovirus infection after pediatric liver transplantation and effectiveness of preemptive therapy.

Cytomegalovirus (CMV) infection is the most common infection following pediatric liver transplantation (LT). Preemptive therapy (PET) is an approach to initiate antiviral treatment for asymptomatic early CMV viremia detected by surveillance testing. However, data on CMV infection after PET are scarce, and the optimal cut-off remains controversial. This study aimed to evaluate the incidence, risk factors, and consequences of CMV infection in pediatric LT using 2 different viral load (VL) cut-offs. We retrospectively reviewed patients aged 0-18 years who underwent LT at Ramathibodi Hospital between March 2001 and August 2020. Demographic data, CMV infection, CMV treatment, and consequences of CMV infection were collected. CMV viremia was monitored by a quantitative nucleic acid amplification test. Clinical outcomes were compared after starting antiviral therapy at a low (>400 but <2000IU/mL) and a high VL cut-off (≥2000IU/mL). A total of 126 patients were included. CMV infection was 71% (90/126), with an incidence rate of 5.5 per 1000 patient-day. Higher tacrolimus and prednisolone dosages were associated with CMV infection with an adjusted hazard ratio of 1.2 (95%CI 1.0-1.4, p=.02) and 2.4 (95%CI 1.9-3.4, p<.001), respectively. The consequences of CMV infection did not differ significantly for the low and high CMV VL cut-off groups. CMV infection in LT recipients is common and is associated with higher tacrolimus and corticosteroid dosage. Additionally, using the CMV VL cut-off at 2000IU/mL to initiate antiviral therapy is practical and effective in preventing CMV disease.

Effect of Cytomegalovirus Infection on Initial Presentation and Overall Prognosis of Biliary Atresia Patients.

Biliary atresia is known to have a multifactorial etiology and perinatal infection with hepatotropic viruses such as cytomegalovirus (CMV) is a probable trigger in a subset of patients. The aim of the current study is to evaluate the effects of CMV association of biliary atresia on the initial presentation of patients and their response to Kasai portoenterostomy. We conducted a retrospective, single-center study on 20 patients of biliary atresia and classified them into two groups based on their CMV immunoglobulin M (IgM) positivity. We compared the age of initial presentation, the liver biochemistry at presentation, immediate and delayed follow-up, rate of jaundice clearance following Kasai portoenterostomy, and histopathology of liver between the two groups. Data were reported in terms of means, and P < 0.05 was considered significant. Out of 20 cases of biliary atresia, 60% (n = 12) were CMV IgM positive. Infants with CMV-positive status were noted to be older at presentation (88.5 days [65-150 days] vs. 83 days [45-160 days] P < 0.05) were more jaundiced at presentation (total bilirubin - 13.51 mg/dl [9.09-15.99 mg/dl] vs. 11.83 mg/dl [6.5-13.5 mg/dl] P < 0.05), had higher alkaline phosphatase (751.2 IU/L [387-1951 IU/L] vs. 621.75 IU/L [172-857 IU/L] P < 0.05), higher gamma-glutamyl transferase levels (505.58 IU/L [376-1127 IU/L] vs. 376.75 IU/L [186-624 IU/L] P < 0.05), and had higher incidence of splenomegaly. The rate of resolution of jaundice postKasai portoenterostomy was also evidently less in CMV-positive patients. Four out of 12 patients have bilirubin >2 mg/dl at a 6-month follow-up. CMV-associated biliary atresia patients have delayed initial presentation and impaired jaundice clearance postKasai portoenterostomy. The role of antiviral therapy should be studied in this subset of patients.

Effects of cytomegalovirus infection on infants' hearing and speech development

Objective:To investigate the effects of cytomegalovirus（CMV） infection on infants' hearing and speech development. Methods:A total of 192 infants with cytomegalovirus infection were selected as research objects（CMV group）. Among 320 normal infants who received physical examinations in the Second Affiliated Hospital of Zhengzhou University during the same period were selected as the control group. Using transiently evoked otoacoustic emission to conduct initial hearing screening. Jointing automatic auditory brainstem response screening method to follow up for infants infected with cytomegalovirus. Those who failed to pass the screening were diagnosed with auditory brainstem response and acoustic immittance examination. The two groups of infants were evaluated for follow-up at the age of 12, 24, 36 months using the Gesell Development scale. Results:Hearing screening（initial hearing screening and 42 d hearing re-screening）: CMV group retrospectively failed rates 28.65%（55/192）, 31.77%（61/192）, normal control group retrospectively failed rates 9.06%（29/320）, 4.06%（13/320）, the results of the two groups' hearing screening showed statistically significant differences（P<0.05）. 48 cases of diagnostic ABR were abnormal in CMV group in 3 month's hearing diagnosis, including 11 cases of secretory otitis media, 37 cases of sensorineural hearing loss. Follow-up for 36 months, 192 infants with CMV infection were confirmed congenital SNHL 37 cases（19.27%）, 21 cases of delayed SNHL（10.94%）, a total of diagnosis with SNHL 58 cases（30.21%）. The development quotient（DQ） of CMV group were respectively 92.05±4.68, 86.53±4.46, 85.92±4.82 in 12, 24, 36 months, and the DQ value of the normal control group were respectively 93.10±4.56, 94.35±4.52, 95.03±4.16. At the age of 24, 36 months, the DQ value of two groups' differences were statistically significant（P<0.05）. Conclusion:CMV infection is hearing loss' risk factors. It had the characteristics of volatility, delay and progressive decline. Follow-up should be strengthened for hearing and speech development.

Effect of Cytomegalovirus Infection on the Central Nervous System: Implications for Psychiatric Disorders.

Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latent infections and interacts extensively with the host immune system, potentially contributing to immune activation and inflammation. Given its proclivity for infecting the brain and its reactivation by inflammatory stimuli, CMV is well known for causing central nervous system complications in the immune-naïve (e.g., in utero) and in the immunocompromised (e.g., in neonates, individuals receiving transplants or cancer chemotherapy, or people living with HIV). However, its potentially pathogenic role in diseases that are characterized by more subtle immune dysregulation and inflammation such as psychiatric disorders is still a matter of debate. In this chapter, we briefly summarize the pathogenic role of CMV in immune-naïve and immunocompromised populations and then review the evidence (i.e., epidemiological studies, serological studies, postmortem studies, and recent neuroimaging studies) for a link between CMV infection and psychiatric disorders with a focus on mood disorders and schizophrenia. Finally, we discuss the potential mechanisms through which CMV may cause CNS dysfunction in the context of mental disorders and conclude with a summary of the current state of play as well as potential future research directions in this area.

Functional Changes of T-Cell Subsets with Age and CMV Infection.

Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4−CD8− (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.

Effect of cytomegalovirus infection on moderate and severe ulcerative colitis

AIM: to evaluate the effect of cytomegalovirus (CMV) infection on the course of moderate and severe flare ups of ulcerative colitis (UC).PATIENTS AND METHODS: a prospective cohort single-center study was done in September 2018 — December 2020. The study included patients with moderate and severe flare ups of UC. All patients underwent colonoscopy with biopsy to quantify CMV DNA by polymerase chain reaction (PCR). Subsequently, the patients were divided into subgroups: with the presence of CMV (CMV+) and its absence (CMV–). In the CMV+ subgroup, antiviral therapy was carried out with an assessment of virological, clinical and endoscopic results on the 19th day of therapy, one month after its completion and after 6 months. In the CMV– subgroup these results were evaluated after 6 months only.RESULTS: the study included 126 patients. CMV was detected in 51 (40.5%). At the same time, its presence was not influenced by gender, age, or previous therapy. Laboratory indicators in both subgroups were comparable, as well as the severity of UC. A significant increase in the risk of developing steroid resistance was revealed in CMV+ patients with severe UC attack (OR 1.33, 95% CI: 1.059–19.4). The effectiveness of antiviral therapy was 60.8%. All patients who did not respond to antiviral therapy underwent surgery. At the same time, among patients in whom antiviral therapy was effective (virus eradication was achieved), there was no need for surgery.CONCLUSION: CMV infection significantly increases the likelihood of developing steroid resistance in patients with severe flare up of UC, while all patients who responded to antiviral therapy did not require surgery. Further multicenter randomized trials are needed.

Effect of cytomegalovirus infection on moderate and severe ulcerative colitis

AIM: to evaluate the effect of cytomegalovirus (CMV) infection on the course of moderate and severe flare ups of ulcerative colitis (UC).PATIENTS AND METHODS: a prospective cohort single-center study was done in September 2018 — December 2020. The study included patients with moderate and severe flare ups of UC. All patients underwent colonoscopy with biopsy to quantify CMV DNA by polymerase chain reaction (PCR). Subsequently, the patients were divided into subgroups: with the presence of CMV (CMV+) and its absence (CMV–). In the CMV+ subgroup, antiviral therapy was carried out with an assessment of virological, clinical and endoscopic results on the 19th day of therapy, one month after its completion and after 6 months. In the CMV– subgroup these results were evaluated after 6 months only.RESULTS: the study included 126 patients. CMV was detected in 51 (40.5%). At the same time, its presence was not influenced by gender, age, or previous therapy. Laboratory indicators in both subgroups were comparable, as well as the severity of UC. A significant increase in the risk of developing steroid resistance was revealed in CMV+ patients with severe UC attack (OR 1.33, 95% CI: 1.059–19.4). The effectiveness of antiviral therapy was 60.8%. All patients who did not respond to antiviral therapy underwent surgery. At the same time, among patients in whom antiviral therapy was effective (virus eradication was achieved), there was no need for surgery.CONCLUSION: CMV infection significantly increases the likelihood of developing steroid resistance in patients with severe flare up of UC, while all patients who responded to antiviral therapy did not require surgery. Further multicenter randomized trials are needed.

Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise.

Circulating immune cell numbers and phenotypes are impacted by high-intensity acute bouts of exercise and infection history with the latent herpesviruses cytomegalovirus (CMV). In particular, CMV infection history impairs the exercise-induced mobilization of cytotoxic innate lymphoid cells 1 (ILC1) cells, also known as NK cells, in the blood. However, it remains unknown whether exercise and CMV infection modulate the mobilization of traditionally tissue-resident non-cytotoxic ILCs into the peripheral blood compartment. To address this question, 22 healthy individuals with or without CMV (20–35 years—45% CMVpos) completed 30 min of cycling at 70% VO2 max, and detailed phenotypic analysis of circulating ILCs was performed at rest and immediately post-exercise. We show for the first time that a bout of high-intensity exercise is associated with an influx of ILCs that are traditionally regarded as tissue-resident. In addition, this is the first study to highlight that latent CMV infection blunts the exercise-response of total ILCs and progenitor ILCs (ILCPs). These promising data suggest that acute exercise facilitates the circulation of certain ILC subsets, further advocating for the improvements in health seen with exercise by enhancing cellular mobilization and immunosurveillance, while also highlighting the indirect deleterious effects of CMV infection in healthy adults.

Effect of cytomegalovirus infection on humoral immune responses to select vaccines administered during infancy

Cytomegalovirus (CMV) infection in neonates has been associated with functional exhaustion of T-cells. We explored humoral immune responses from vaccination between congenital CMV-infected, postnatal CMV-infected and CMV-uninfected infants. Whole blood from infants with known CMV status was tested at seven months age, by in-house Luminex multiplex immunoassay, for antibodies to select vaccines in the primary series of childhood immunisations: Diphtheria-Tetanus-acellular Pertussis-Haemophilus Influenzae type b-Hepatitis B (DTaP-Hib-HBV).Immune responses to the primary series of DTaP-Hib-HBV vaccine was similar in congenital CMV-infected, postnatal CMV-infected and CMV-uninfected infants at seven months age. Close to 100% of congenital CMV-infected, postnatal CMV-infected and CMV-uninfected infants had antigen-specific IgG-concentrations above the correlate or surrogate of protection to four of five antigens (HBsAg, TT, DT, PT). This suggests CMV does not have any deleterious effect on humoral immune responses to the primary series of DTaP-Hib-HBV vaccination in black-African children.

Viral infection of the ovaries compromises pregnancy and reveals innate immune mechanisms protecting fertility

Viral infections during pregnancy are a considerable cause of adverse outcomes and birth defects, and the underlying mechanisms are poorly understood. Among those, cytomegalovirus (CMV) infection stands out as the most common intrauterine infection in humans, putatively causing early pregnancy loss. We employed murine CMV as a model to study the consequences of viral infection on pregnancy outcome and fertility maintenance. Even though pregnant mice successfully controlled CMV infection, we observed highly selective, strong infection of corpus luteum (CL) cells in their ovaries. High infection densities indicated complete failure of immune control in CL cells, resulting in progesterone insufficiency and pregnancy loss. An abundance of gap junctions, absence of vasculature, strong type I interferon (IFN) responses, and interaction of innate immune cells fully protected the ovarian follicles from viral infection. Our work provides fundamental insights into the effect of CMV infection on pregnancy loss and mechanisms protecting fertility.

688. Marginal Structure Models to Estimate the Effect of Cytomegalovirus Infection on Hospitalization Among Children Undergoing Allogeneic Hematopoietic Cell Transplantation

BackgroundChildren receiving an allogeneic hematopoietic cell transplant (HCT) are at risk for cytomegalovirus (CMV) infection in the post-transplant period, necessitating routine surveillance for CMV. Some patients will not have CMV detected while others will have intermittent or persistent CMV detection. Prior analyses assessing the association of CMV infection on hospitalization in the post-transplant period have been limited by methods that did not consider the time-varying nature of the exposure (CMV reactivation) and its confounders or aim to obtain causal effect estimates. We aimed to assess the causal effect of CMV reactivation on hospitalization using a causal modeling approach.The Effect of CMV Infection on Hospitalization Using Generalized Estimating Equations and Marginal Structural Models MethodsA cohort of allogeneic HCT patients transplanted at Children’s Hospital of Philadelphia January 2004–April 2017 was assembled and followed for 100 days after transplant. Eligible patients included those under CMV surveillance, defined as having ≥2 CMV whole blood polymerase chain reaction tests in the first month after HCT. All information was abstracted from medical charts. The association of CMV reactivation on the rate of hospitalization was estimated using traditional generalized estimating equations and repeated using a marginal structural model that accounted for time-varying exposure, confounders and non-random drop-out and obtained effects with causal interpretations.ResultsThe study cohort included 340 pediatric allogeneic HCT recipients under CMV surveillance testing. 46.5% were female and the median age was 9 (range: 0 to 26). The CMV infection rate was 33.9%, with a median time to CMV detection of 23.5 days (range: 4-100). CMV infection was common in Donor+/Recipient+ (58.9%) and Donor-/Recipient+ (34.6%) patients. A traditional model estimates an additional week of CMV infection was associated with a 22% increase in average weekly hospitalization (Incidence rate ratio: 1.22, 95%: 1.12 -1.34). A marginal structure model estimates an additional week of CMV infection is associated with 3% increase in average weekly hospitalization incidence (Incidence rate ratio: 1.03, 95%: 0.91-1.16).ConclusionOur research showed the effect of CMV on hospitalization diminished after properly considering the time-varying nature of the CMV infection status and its confounders.Disclosures Brian T. Fisher, DO, MPH, MSCE, Astellas (Advisor or Review Panel member)Merck (Grant/Research Support)Pfizer (Grant/Research Support)

Effects of cytomegalovirus infection on the differential diagnosis between biliary atresia and intrahepatic cholestasis in a Chinese large cohort study

Introduction and objectivesDifferentiating biliary atresia from other causes of neonatal cholestasis is challenging, particularly when cytomegalovirus (CMV) and biliary atresia occur simultaneously. We aimed to elucidate whether CMV infection would affect the differential diagnosis of biliary atresia and intrahepatic cholestasis. Patients and methodsThis retrospective study was conducted among patients with neonatal cholestasis admitted to three tertiary hospitals between January 2010 and August 2019. The clinical characteristics, laboratory, and imaging findings were recorded. On the basis of the CMV serology results, the infants were classified into CMV-IgM (+) and CMV-IgM (−) groups. The clinical differences and diagnostic performances of routine predictors between biliary atresia and intrahepatic cholestasis were analyzed in each group. Finally, we compared the diagnostic performances of various tests in the two groups. ResultsA total of 705 patients with neonatal cholestasis were enrolled: 215 (30.5%) patients were positive for CMV-IgM, among whom 97 had biliary atresia and 118 had CMV hepatitis; 490 infants were CMV-IgM (−), among whom 240 had biliary atresia and 250 had intrahepatic cholestasis. The diagnostic performances of stool color, direct bilirubin level, γ-glutamyl transpeptidase level, abnormal gallbladder, triangular cord sign, and hepatobiliary scintigraphy between CMV hepatitis and CMV-IgM (+) biliary atresia were similar to those between CMV-IgM (−) biliary atresia and CMV-IgM (−) intrahepatic cholestasis groups. ConclusionsOur large-scale study showed a high prevalence of CMV infection in patients with neonatal cholestasis in China. The presence of CMV infection did not affect the routine predictors to discriminate biliary atresia and intrahepatic cholestasis.

Effects of cytomegalovirus infection on extravillous trophoblast cells invasion and immune function of NK cells at the maternal-fetal interface.

Cytomegalovirus (CMV) is one of the most common intrauterine infection virus, which can cause intrauterine transmission through the placenta, resulting in abortion, stillbirth and congenital malformations. In this study, the co‐culture extravillous trophoblast (EVT) HTR8/SVneo cell model of CMV infection was established in vitro. The toxicity of CMV infected EVT was determined, and then, the cell invasion experiment was conducted to evaluate the effect on the invasion ability of EVT cell lines. Western blot and real‐time PCR were used to detect the related cytokines in the PI3K/AKT signalling pathway in cells. Flow cytometry was used to detect the immune function related factors of the supernatant of CMV culture on decidual NK cells. The TCID50 of CMV virus was 10−5.4. The results of immunofluorescence showed that a large number of fluorescent green of CMV pp65 antigen signals appeared in the cytoplasm of CMV infection group. CMV could infect and replicate EVT cells and inhibited cell proliferation. The expression of proteins PDK1, AKT‐S473 and AKT‐S308 was significantly increased in CMV infection group. The levels of IL‐17, IL‐4 and IFN‐γ were 8.7 ± 0.48%, 12.17 ± 0.61% and 6.66 ± 0.25%, respectively, in CMV infection group. The above results indicated that CMV infection inhibited EVT cells proliferation, weakened the invasion ability and inhibited the immune function of NK cells at the maternal‐fetal interface, resulting in the abnormal maternal‐fetal crosstalk.

Cytomegalovirus Experience in Pediatric Kidney Transplantation in 26 Years’ Time

IntroductionIn this study,we investigated the presence of cytomegalovirus (CMV) infection in kidney transplanted children and its effect on kidney dysfunction. Material and MethodsOne hundred thirty-five pediatric renal transplant patients were included in this study. The presence of CMV infection, CMV risk status, and other clinical features of the patients were evaluated retrospectively. ResultsFifty-three percent of all patients and 68.8% of patients with CMV were male. The mean age was 12 years in all patients and CMV groups. According to the CMV risk classification, 40.9% of the patients with CMV infection/disease were in the high-risk group (CMV D+R-). In CMV risk groups, the presence of CMV infection/disease was similar. Cold ischemia time, male sex (patients and donors), deceased donor, higher HLA-mismatches, and cumulative antithymocyte globulin dose were found as risk factors for CMV infection/disease. Acute rejection/graft failure was observed in 27% of all patients. CMV infection has no effect on rejection/graft failure and survival. DiscussionThe frequency and risk factors of CMV in renal transplant children in our study were consistent with the literature. ConclusionsCMV infection was found in one-fifth of our patients and the majority (71.9%) of them developed infection in the first 6 months. In one-third of our patients acute rejection/graft failure was observed. There was no effect of CMV infection on rejection/graft failure and survival in pediatric patients with proper and effective treatment.

Correlation of Longitudinal Gene-Expression Profiling (GEP) Score to Cytomegalovirus (CMV) Infection: Results from the Outcomes Allomap® Registry

Cytomegalovirus (CMV) infection has been implicated in the pathogenesis of allograft rejection, which is reflected by high gene-expression profiling (GEP) scores. The effect of CMV infection on serial GEP scores in the absence of acute cellular rejection (ACR) is unknown. Data from 14,985 samples collected from 2288 heart transplant (HT) recipients enrolled in Outcomes AlloMap® Registry (OAR) were analyzed. The empirical distribution of GEP scores at the visit closest to CMV infection were compared to GEP scores obtained at other visits via Kolmogorov-Smirnov tests. AlloSure measurements from those who underwent concurrent dd-cfDNA testing were also reviewed. 311 samples were collected from 213 patients with CMV infection at the time of GEP testing. The mean time to CMV infection from transplant was 346 days. Median GEP score at the time of diagnosis of CMV infection was significantly higher when compared to GEP score obtained at other visits (34 v 30, p<; 0.0001) (Figure 1). For patients with samples assessed via AlloMap and AlloSure, there was no significant difference in the distribution of AlloSure measurements at the time of CMV infection (Figure 2). CMV infections in HT recipients are associated with an increase in GEP score independent of associated ACR. The likely mechanism is immune activation/modulation of one or more of the 11 genes in the GEP signature. Hence, CMV status should be considered when clinically interpreting high GEP scores. AlloSure testing in conjunction with AlloMap demonstrates AlloSure is invariant to CMV infection.

SAT-342 CYTOMEGALOVIRUS INFECTION IN KIDNEY TRANSPLANTS RECIPIENTS: EXPERIENCE OF A SINGLE CENTER

Cytomegalovirus (CMV) is the most common infection after organ transplantation; it can be a major cause of morbidity, mortality. Optimal prevention, diagnosis, and treatment of active CMV infection enhance transplant outcomes. But, the management of CMV varies considerably among transplant centers. We described the incidence, clinical profile, outcome, and risk factors for the development of CMV infection among renal transplant recipients. We studied kidney transplants recipients admitted for CMV infection from January 1998 to September 2018. CMV infection was present if the patient had positive CMV antigenemia or positive PCR CMV. CMV disease was diagnosed if clinical signs and symptoms are associated with CMV infection. About 48 cases of CMV infection was confirmed in our study. The majority of patients were CMV seropositive recipients from seropositive donors (88,8%). Only 29, 16% of our patients had symptomatic CMV infection and 70, 8% had CMV disease. 52, 1% of our recipients developed CMV infection 2 months post-transplantation. Fever was the most common presenting symptoms (97, 2%) and the most common biological disorder were leukopenia (83,3%). Among the 6 who developed tissue-invasive CMV (13,3%), 3 had CMV pneumonitis, 1 has two recurrent episodes of CMV uveitis for, 1 had colitis, and 1 had macrophage activation syndrome induced by CMV during pregnancy. Risk factors that were statistically significant in the development of CMV disease were as follows: recent rejection treatment (p= 0,021) and HLA mismatch (p=0, 05). For the indirect effect of CMV infection, the most frequent was bacterial and fungal coinfections (33, 35%), then we found, graft dysfunction (25%), acute graft rejection (14, 5%), new-onset post-transplant diabetes (6, 25%), post lymphoproliferative disease (1 case, 2, 2%), and mortality incidence was 20%. The cardiovascular events were significantly associated with CMV infection (p=0.02). We also demonstrate a significant association between CMV infection and long term graft function expressed either as graft dysfunction or graft loss: The DFG was lower in CMV infection group in 6 months, 1 year, 2 years and 10 years. The graft loss was significantly superior in patients with CMV infection/disease than patients without CMV (p= 0,05). CMV infection and CMV disease remain an infectious cause of significant clinical problems, morbidity, and mortality. Despite the absence of prophylaxis, the complications associated with CMV infection are usually not higher than in other countries. However, the use of universal prophylaxis and preemptive therapy remains necessary to reduce the hospitalization rate and consequence of CMV infection.

Effect of cytomegalovirus infection on the content of myristic acid and sphingomyelin in the blood of the umbilical cord of newborns

Effect of cytomegalovirus infection on the content of myristic acid and sphingomyelin in the blood of the umbilical cord of newborns

Immunometabolic phenotype of BV-2 microglia cells upon murine cytomegalovirus infection.

Microglia are resident brain macrophages with key roles in development and brain homeostasis. Cytomegalovirus (CMV) readily infects microglia cells, even as a possible primary target of infection in development. Effects of CMV infection on a cellular level in microglia are still unclear; therefore, the aim of this research was to assess the immunometabolic changes of BV-2 microglia cells following the murine cytomegalovirus (MCMV) infection. In light of that aim, we established an in vitro model of ramified BV-2 microglia (BV-2∅FCS, inducible nitric oxide synthase (iNOSlow), arginase-1 (Arg-1high), mannose receptor CD206high, and hypoxia-inducible factor 1α (HIF-1αlow)) to better replicate the in vivo conditions by removing FCS from the cultivation media, while the cells cultivated in 10% FCS DMEM displayed an ameboid morphology (BV-2FCS high, iNOShigh, Arg-1low, CD206low, and HIF-1αhigh). Experiments were performed using both ramified and ameboid microglia, and both of them were permissive to productive viral infection. Our results indicate that MCMV significantly alters the immunometabolic phenotypic properties of BV-2 microglia cells through the manipulation of iNOS and Arg-1 expression patterns, along with an induction of a glycolytic shift in the infected cell cultures.