Risk Factors For Cytomegalovirus Infection Research Articles

QuantiFERON monitor predicts early cytomegalovirus infection and viral burden in allogeneic hematopoietic stem cell transplantation.

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

Bridging the gap: assessing CMV DNAemia in kidney transplant recipients with previous solid organ transplants.

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive regimens. The aim of this retrospective single-center study was to investigate the incidence and implications of CMV DNAemia in KTRs with prior SOTs. The study included 97 KTRs with prior SOTs and 154 KTRs with no prior transplants as a control group. In the study group, the most common SOT before the current kidney transplantation (KT), was a previous KT. Patients in the KTR group with prior SOTs were more sensitized than those in the control group [calculated panel-reactive antibody > 30%: 49 (50.5%) vs. 30 (19.45%) patients, p = 0.001]. There was a 39.2% incidence of CMV DNAemia in the previous SOT group compared to 48.7% in the control group [non-significant (NS)]. Patients with prior SOTs demonstrated a shorter post-transplant time to CMV DNAemia [median time 1.6 months (interquartile range, IQR 0.7-5.8) in the KTRs with prior SOTs vs. 2.6 months (IQR 1.5-8.1) in the control group (p = 0.001)]. Although the study highlights the need for tailored prophylaxis strategies and vigilant monitoring in KTRs with prior SOTs, its limitations, such as its retrospective nature and single-center design, call for further multicenter research to establish comprehensive guidelines for managing CMV DNAemia in this unique patient population. Despite these limitations, this study underscores the importance of recognizing the heightened risk of CMV infection or reactivation in KTRs overall and the potential benefits of proactive intervention to mitigate associated morbidity and mortality.

Clinical impact and risk factors for cytomegalovirus infection in deceased donor liver transplantation without prophylaxis: Single center experience

Clinical impact and risk factors for cytomegalovirus infection in deceased donor liver transplantation without prophylaxis: Single center experience

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan

BackgroundCytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. MethodsThis retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. ResultsThere were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. ConclusionThe study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Risk factors of cytomegalovirus infection in patients with failed corneal grafts

Objective: To investigate the levels of cytomegalovirus (CMV) infection and associated risk factors in corneal transplant recipients who experienced transplant failure. Methods: This was a case-control study. Clinical data from 576 cases (576 eyes) of patients who underwent repeat corneal transplant surgery at the Department of Ophthalmology, Peking University Third Hospital, due to corneal transplant failure from January 2016 to May 2022 were collected. Of these, 305 were male and 271 were female, with a median age of 44.0 (0.7, 91.0) years. The CMV infection rate was analyzed based on the detection of CMV DNA in aqueous humor or corneal tissue during corneal transplant surgery. Patients were divided into the CMV group (CMV DNA positive) and the control group (herpes virus DNA negative). The main research indicators included the CMV infection rate, clinical characteristics, and risk factors in corneal transplant recipients. Chi-square tests and binary logistic analysis were used to compare differences between the two groups in general information, systemic diseases, ocular lesions, ocular surgical history, and local and systemic medications. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each CMV infection risk factor. Results: The overall CMV infection rate was 21.9%(126/576), with annual rates ranging from 10.9% to 37.7% from 2016 to 2021. After applying inclusion and exclusion criteria, 378 patients were included in the control trial, with 126 in the CMV group and 252 in the control group. Statistically significant differences between the two groups were observed in systemic immune-related corneal lesions [CMV group: 38 (30.2%), control group: 26 (10.3%)], local immune and inflammatory corneal lesions [CMV group: 46 (36.5%), control group: 40 (15.9%)], congenital corneal opacity [CMV group: 46 (36.5%), control group: 48 (19.0%)] total number of corneal transplants (CMV group: 178 times, control group: 276 times), corneal deep neovascularization crossing the graft [CMV group: 104 (82.5%), control group: 68 (27.0%)] and severe opacity [CMV group: 44 (34.9%), control group: 30 (11.0%)]. Binary logistic regression analysis showed that systemic immune-related corneal lesions (OR=4.044, 95%CI 1.810-9.033, P<0.001), local immune and inflammatory corneal lesions (OR=3.554, 95%CI 1.569-8.052, P=0.002), congenital corneal opacity (OR=2.606, 95%CI 1.216-5.589, P=0.014), total number of corneal transplants (OR=3.206, 95%CI 1.753-5.864, P<0.001), corneal deep neovascularization crossing the graft (OR=8.347, 95%CI 3.967-17.559, P<0.001), and severe opacity (OR=3.063, 95%CI 1.221-7.682, P=0.017) were independent risk factors for CMV infection after corneal transplant. Conclusions: CMV infection was present in more than 1/5 of corneal transplant recipients who experienced transplant failure. CMV infection after corneal transplant may be related to immune rejection reactions and ocular inflammatory responses. Inflammatory corneal lesions associated with systemic or local immune abnormalities, congenital corneal opacity, and multiple corneal transplants may exacerbate the levels of inflammatory factors during the perioperative period of corneal transplant, increasing the risk of post-transplant CMV infection, leading to the infiltration of deep neovascularization and severe opacity in the cornea.

Periodontal pockets as a risk factor for cytomegalovirus infection after kidney transplantation: single-center retrospective analysis

Periodontal pockets as a risk factor for cytomegalovirus infection after kidney transplantation: single-center retrospective analysis

ABO incompatibility is a risk factor for cytomegalovirus infection with living donor liver transplantation

ABO incompatibility is a risk factor for cytomegalovirus infection with living donor liver transplantation

Risk Factors for CMV Infection, Including HLA Disparity and Ptcy Transplant in the Era of Letermovir Prophylaxis

Reports suggest that post-transplant cyclophosphamide (PTCy) for haploidentical and HLA-matched sibling donor allogeneic stem cell transplant (allo-SCT) is associated with a higher incidence of cytomegalovirus (CMV) infection than calcineurin inhibitor (CNI) for HLA-matched sibling donor allo-SCT. Prophylactic letermovir has been shown effective for CMV seropositive patients, based on the data mostly before the FDA approval of letermovir (2017). We reevaluated the risk of CMV infection in PTCy transplants. We retrospectively analyzed 175 patients after allo-SCT between May 2019-May 2022). CMV infection was monitored at least for the first year by serostatus, viral load over 500 IU/mL, and/or evidence of CMV end-organ disease. Univariate and multivariate Cox regression analyses were used for the factors, including CMV serostatus, use of letermovir, GVHD prophylaxis, and HLA disparities, to affect the risk of CMV infection and graft-versus-host disease (GVHD)-free relapse-free survival (GRFS). Cumulative incidence curves were used to visualize the incidence of CMV infection stratified by HLA match and PTCY use. A landmark analysis at Day +100 was used for GRFS, where patients who had CMV infection beyond Day +100 (N=13) were assigned to the no-infection group. Of the 175 patients, 108 received HLA-matched donors with GVHD prophylaxis, either CNI (N=70) or PTCy (N=38), while 67 received HLA mismatched donors with either CNI (n=6) or PTCy (N=66) ( Table). Letermovir was given to 137 patients (CMV IgG positive N=130, negative N=7) but not to 38 patients (CMV IgG positive N=12, negative N=26). CMV infection occurred in 28 patients (CMV IgG positive N= 28, CMV IgG negative N=0) before or after Day +100 (N=15 or N=13, respectively). CMV IgG positive recipients not receiving letermovir demonstrated a higher risk of infection by Day +100 than those receiving letermovir (Hazard ratio (HR) 10.1 (95% confidence interval (CI) 3.6-28.6), p&amp;lt;0.01). All 13 infections after Day +100 occurred after the cessation of letermovir (median: 82.9 days after cessation). On univariate analysis, PTCy and HLA mismatch donors increased the risk of CMV infection. The risk of infection by Day +100 increased with PTCy (p=0.07). The risk of infection after Day +100 increased with HLA mismatch donors (p=0.05). In addition, it was confirmed that HLA mismatch allo-SCT with PTCy increased the risk of CMV infection over matched allo-SCT with CNI ( Figure, HR 4.6 (95% CI 1.6-11.9), p&amp;lt;0.01), while HLA match allo-SCT with PTCy did not (p=0.3) (Figure 1). The trend was similar when analyzed only in the case of CMV infection by Day +100 (p&amp;lt;0.05) and after Day +100 (p=0.1). In the 130 CMV IgG seropositive patients who received letermovir, multivariate analysis showed that HLA mismatch donors with PTCy increased the risk of CMV infection over HLA match allo-SCT with CNI. When analyzed only for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome with letermovir (N=91), HLA mismatch transplant with PTCy increased the risk of CMV infection over HLA match transplant with CNI (p=0.05), but not for HLA match transplant with PTCy. Landmark analysis demonstrated better GRFS in the PTCy group than the CNI group and in patients who received PTCy with CMV infection than those who received CNI without CMV infection (p&amp;lt;0.01). PTCy increased the incidence of CMV infection in HLA mismatch allo-SCT by D+100 but not HLA match allo-SCT in the era of letermovir prophylaxis. Patients with PTCy transplant who overcome CMV infection have improved GRFS, possibly due to the increased graft-versus-leukemia effect. Further analysis is required to confirm the difference in the incidence of CMV infection between HLA match and mismatch transplant with PTCy and to assess the significance of late CMV (after Day +100) infection on GRFS.

High-dose aciclovir in CMV infection prophylaxis after allogeneic HSCT: a single-center long-term experience

There is only limited data on cytomegalovirus (CMV) prophylaxis with high-dose (HD) aciclovir after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a retrospective analysis on a total of 179 patients who underwent their allo-HSCT with HD-aciclovir prophylaxis at our center. A clinically significant CMV infection (cs-CMVi) was observed in 56 (31%) cases with a median time of 49 (range 25–147) days after HSCT. A significantly higher CMV infection rate was observed in seropositive recipients with a seronegative donor (74%) compared to seropositive recipients with a seropositive donor, and seronegative recipients with seropositive and seronegative donors (24%, 18%, 7% respectively; p < 0.001). The CMV serostatus was the only significant risk factor for CMV infection in our analysis. CMV disease developed in three patients with CMV-related death in two cases. During HD-aciclovir prophylaxis, we did not observe any medical condition attributable to HD-aciclovir’s adverse effects. Compared to published results, we observed a low incidence of cs-CMVi with HD-aciclovir prophylaxis in several patient subgroups, especially in seropositive recipients with a seropositive donor. With respect to the determined threshold, HD-aciclovir prophylaxis seems to have good efficacy in an intermediate cs-CMVi risk patients, but prospective randomized trials would be needed for definite conclusions.

The Association of Cytomegalovirus and Allostatic Load by Country of Birth and Length of Time in the United States.

Cytomegalovirus (CMV) is a highly prevalent virus with a worldwide distribution. It typically remains dormant in most individuals until reactivation. Immunocompromised states are known to be potential causes for CMV reactivation. Current research has shown a link in the decline of immigrant health among those living in the US for an extended period, though the impact of CMV on this is not clear. This study investigated the association between country of birth, duration of US residency, allostatic load, and latent cytomegalovirus infection (CMV IgG) in a sample of US adults aged 20-49. The data utilized for our analysis was obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Allostatic load, an index measuring the cumulative physiological strain on the body as it strives to regain stability in the presence of chronic stress, provided a valuable approach to assess stress within the context of CMV exposure. Logistic regression modeling was employed to estimate odds ratios and confidence intervals for the analysis. The chi-square test of association and Cramer's V statistic were used to assess the correlation among categorical variables, while Pearson's correlation coefficient was applied to evaluate the relationship between continuous variables. The results revealed that individuals born outside the US and those with less than 20 years of residency in the US exhibited significantly higher proportions of positive CMV IgG compared to individuals born in the US. Specifically, individuals born outside the US had more than triple the odds of CMV IgG when adjusting for the AL index (OR = 3.69, p-value = 0.0063). A similar trend was observed when examining AL risk based on the duration of US residency. Furthermore, age and sex were identified as significant predictors (p-value < 0.05) of AL risk, considering the individual's country of birth. In summary, the findings of this study significantly enhance our comprehension of the intricate interplay between cytomegalovirus (CMV) and allostatic load (AL). The investigation sheds light on how CMV and AL interact within specific demographic contexts, providing valuable insights into the underlying risk factors for CMV infection.

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.

Clinical Study of Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival. A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed. For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005). The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.

Risk Factors for Cytomegalovirus Infection and Its Impact on Survival after Living Donor Liver Transplantation in South Korea: A Nested Case-Control Study.

Cytomegalovirus (CMV), a common pathogen, causes infectious complications and affects long-term survival after transplantation. Studies examining living donor liver transplantation (LDLT) are limited. This study analyzed the risk factors for CMV infection and its impact on the survival of LDLT patients. A nested case-control design retrospectively analyzed data from 952 patients who underwent LDLT from 2005-2021. The incidence of CMV infection for the study cohort was 15.2% at 3 months for LDLT patients managed preemptively. Patients with CMV infections were matched with those without the infection at corresponding time points (index postoperative day) in a 1:2 ratio. Graft survival was significantly lower in the CMV infection group than in the control group. CMV infection was an independent risk factor for graft survival in the matched cohort (HR 1.93, p = 0.012). Independent risk factors for CMV infection were female sex (HR 2.4, p = 0.003), pretransplant MELD (HR 1.06, p = 0.004), pretransplant in-hospital stay (HR 1.83, p = 0.030), ABO incompatibility (HR 2.10, p = 0.009), donor macrovesicular steatosis ≥10% (HR 2.01, p = 0.030), and re-operation before index POD (HR 2.51, p = 0.035). CMV infection is an independent survival risk factor, and its risk factors should be included in the surveillance and treatment of CMV infections after LDLT.

Incidence of post-transplant cytomegalovirus viremia in patients receiving lungs after ex vivo lung perfusion

ObjectivesCytomegalovirus infection after lung transplant is associated with increased morbidity and mortality. Inflammation, infection, and longer ischemic times are important risk factors for cytomegalovirus infection. Ex vivo lung perfusion has helped to successfully increase the use of high-risk donors over the last decade. However, the impact of ex vivo lung perfusion on post-transplant cytomegalovirus infection is unknown. MethodsWe performed a retrospective analysis of all adult lung transplant recipients from 2010 to 2020. The primary end point was comparison of cytomegalovirus viremia between patients who received ex vivo lung perfusion donor lungs and patients who received non–ex vivo lung perfusion donor lungs. Cytomegalovirus viremia was defined as cytomegalovirus viral load greater than 1000 IU/mL within 2 years post-transplant. Secondary end points were the time from lung transplant to cytomegalovirus viremia, peak cytomegalovirus viral load, and survival. Outcomes were also compared between the different donor recipient cytomegalovirus serostatus matching groups. ResultsIncluded were 902 recipients of non–ex vivo lung perfusion lungs and 403 recipients of ex vivo lung perfusion lungs. There was no significant difference in the distribution of the cytomegalovirus serostatus matching groups. A total of 34.6% of patients in the non–ex vivo lung perfusion group developed cytomegalovirus viremia, as did 30.8% in the ex vivo lung perfusion group (P = .17). There was no difference in time to viremia, peak viral loads, or survival when comparing both groups. Likewise, all outcomes were comparable in the non–ex vivo lung perfusion and ex vivo lung perfusion groups within each serostatus matching group. ConclusionsThe practice of using more injured donor organs via ex vivo lung perfusion has not affected cytomegalovirus viremia rates and severity in lung transplant recipients in our center.

Sero-prevalence and risk factors for cytomegalovirus infection among pregnant women in a teaching hospital in Ogun state, Nigeria

Background: Infection with cytomegalo virus is usually asymptomatic however in pregnant women the risk of congenital infection and foetal abnormalities makes antenatal screening for CMV infection necessary. The aim of this study was to determine the sero-prevalence and risk factors for CMV infection among pregnant women in Babcock University Teaching Hospital (BUTH), Ilishan Remo, Ogun State, Nigeria.Methods: The study was a cross-sectional descriptive study conducted between January and May, 2017 on patients attending the antenatal clinic of Babcock University Teaching Hospital. Enzyme Linked Immunosorbent Assay (ELISA) Kits were used to determine IgM and IgG anti CMV antibody titresinvenous blood samples obtained from study participants.Results: A total of 80 patients were recruited into the study. The mean age was 30 years.All (100%) respondents were sero-positive for anti CMV IgG antibodies while 28.75% of respondents were seropositive for anti CMV IgM antibodies.Conclusion: There was a highsero-prevalence rate of CMV infection in the study. Screening of pregnant women for CMV infection is necessary due to the risk of congenital infection and fetal defects.

Steroid Resistance/Dependence Might Be an Alarming Feature for Cytomegalovirus Infection Among Ulcerative Colitis Patients With Increased Disease Activity.

Background/Aims This study aimed to determine the prevalence of cytomegalovirus (CMV) infection among patients with moderate to severe active ulcerative colitis (UC) and to determine the risk factors for CMV infection according to the demographic features of these patients. Patients/Methods A total of 183 patients with severe or moderate active UC were enrolled in the study after retrospective analysis. The disease severity of UC was determined according to the Mayo Score. CMV infection was investigated by real-time quantitative polymerase chain reaction (PCR) and the immunohistochemical (IHC) staining method in colonic mucosal biopsies. Results CMV infection was diagnosed in 33.9% of patients with UC. UC patients diagnosed with CMV infection had significantly higher Mayo Score levels (9.68 vs 8.56 and p=0.001). The long-term presence of UC disease, steroid, azathioprine (AZA), and anti-tumor necrosis factor-alpha (anti-TNF-alpha) usage increased the risk of CMV infection (p=0.001 and odds ratio=1.168; p=0.001 and odds ratio=2.967; p=0.004 and odds ratio=2.953; p=0.003 and odds ratio=3.861, respectively). CMV infection increases the risk of developing steroid resistance or dependency (p=0.002 and odds ratio=3.147; p=0.002 and odds ratio=5.085, respectively). Post-treatment clinical remission and mucosal healing rates were higher in CMV-negative patients than in CMV-positive patients (99.2% vs 91.9%, p=0.018 and 86.8% vs 70.9%, p=0.015). A higher rate of need for colectomy had been found in patients with CMV infection (5 patients vs 1 patient; p=0.034 and odds ratio=10.526). Conclusions The presence of CMV infection increases the severity of the diseaseand worsens clinical outcomes, leading to adverse treatment outcomes. CMV infection increases the requirement for colectomy. The presence of steroids, immunosuppressives such as AZA, and anti-TNF-alpha usage increases the occurrence of CMV infection. CMV infection should be suspected in patients with moderate to severe UC activity.

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children's patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study.

Cytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite improvement by pre-emptive antivirus treatment. CMV-specific cytotoxic T lymphocytes (CMV-CTL) are universally used and proven well-tolerance after allo-HSCT in adult clinical trials. However, it is not comprehensively evaluated in children's patients. Herein, we conducted a retrospective study to determine the risk factors of CMV infection and evaluation of CMV-CTL in children patients who underwent allo-HSCT. As result, a significantly poor 5-year overall survival was found in the CMV infection group (87.3 vs. 94.6%, p=0.01). Haploidentical HSCT (haplo-HSCT) was identified as an independent risk factor for CMV infection through both univariate and multivariate analyses (p&lt;0.001, p=0.027, respectively). Furthermore, the cumulative incidence of CMV infection was statistically higher in the haplo-HSCT group compared to the HLA-matched donor group (44.2% vs. 21.6%, p&lt;0.001). Finally, the overall response rate of CMV-CTL was 89.7% (26/29 patients) in CMV infection after allo-HSCT. We concluded that CMV infection following allo-HSCT correlated with increased mortality in children's patients, and haplo-HSCT was an independent risk factor for CMV infection. Adoptive CMV-CTL cell therapy was safe and effective in pediatric patients with CMV infection.

Analysis of risk factors and prognosis of cytomegalovirus infection post umbilical cord blood stem cell transplantation in children with primary immunodeficiency diseases

Objective: To investigate the risk factors and outcomes of cytomegalovirus (CMV) infection post umbilical cord blood stem cell transplantation (UCBT) in children with primary immunodeficiency diseases (PID). Methods: Clinical data of 143 PID children who received UCBT in the Children's Hospital of Fudan University from January 2015 to June 2020 were collected retrospectively. CMV-DNA in the plasma was surveilled once or twice a week within 100 days post-UCBT. According to the CMV-DNA test results, children were divided into the CMV-infected group and the CMV-uninfected group. The incidence and risk factors of CMV infection were analyzed. At 1-month post-UCBT, the absolute lymphocyte count, ratio of lymphocyte subsets and immunoglobulin levels were compared between those whose CMV infection developed 1-month later post-UCBT and those not. Mann-Whitney U test and chi-squared test were used for comparision between groups. Kaplan-Meier survival analysis was used to analyze the impact of CMV infection on survival. Results: Among 143 patients, there were 113 males and 30 females, with a age of 14 (8, 27) months at UCBT. Chronic granulomatosis disease (n=49), very-early-onset inflammatory bowel disease (n=43) and severe combined immunodefiency (n=29) were the three main kinds of PID. The rate of CMV infection was 21.7% (31/143), and the time of infection occurring was 44 (31, 49) days post-UCBT. The incidence of recurrent CMV infection was 4.2% (6/143) and refractory CMV infection was 4.9% (7/143).There was no significant difference in the first time CMV-DNA copy and peak CMV-DNA copy during treatment between the recurrent CMV infection group and the non-recurrent CMV infection group (32.8 (18.3, 63.1)×106 vs. 22.5 (13.2, 31.9)×106 copies/L, Z=-0.95, P=0.340;35.2 (20.2, 54.6)×106 vs. 28.4 (24.1, 53.5)×106copies/L, Z=-0.10, P=0.920), so were those between the refractory CMV infection group and non-refractory CMV infection group (21.8 (13.1, 32.2)×106 vs. 25.9 (14.2, 12.2)×106copies/L, Z=-1.04, P=0.299; 47.7 (27.9, 77.6)×106 vs. 27.7 (19.7,51.8)×106copies/L, Z=-1.49, P=0.137). The CMV-infected group accepted more reduced-intensity conditioning (RIC) regimen than the CMV-uninfected group (45.2% (14/31) vs. 25.0% (28/112), χ2=4.76, P<0.05). The rate of CMV-seropositive recipients and Ⅱ-Ⅳ acute graft versus host diseases (aGVHD) are significantly higher in the CMV-infected group than the CMV-uninfected group (100% (31/31) vs. 78.6% (88/112), 64.5% (20/31) vs. 26.8% (30/112), χ2=7.98,15.20, both P<0.05). The follow-up time was 31.6 (13.2, 45.9) months, CMV infection had no effect on overall survival (OS) rate (χ2=0.02, P=0.843). There was significant difference in the survival rate among three groups of refractory CMV infection, non-refractory CMV infection and the CMV-uninfected (4/7 vs.95.8% (23/24) vs. 86.6% (97/112), χ2=5.91, P=0.037), while there was no significant difference in the survival rate among three groups of recurrent CMV infection, non-recurrent CMV infection and the CMV-uninfected (5/6 vs. 88.0% (22/25) vs. 86.6% (97/112), χ2=0.43, P=0.896). Children who developed CMV infection after 30 days post-UCBT had lower absolute count and rate of CD4+ T cells and immunoglobulin G (IgG) level than those in the CMV-uninfected group (124.1 (81.5, 167.6) ×106 vs. 175.5 (108.3, 257.2) ×106/L, 0.240 (0.164, 0.404) vs. 0.376 (0.222, 0.469), 9.3 (6.2, 14.7) vs. 13.6 (10.7, 16.4) g/L, Z=-2.48, -2.12,-2.47, all P<0.05), but have higher rate of CD8+T cells than those in CMV-uninfected group (0.418 (0.281, 0.624) vs. 0.249 (0.154, 0.434), Z=-2.56, P=0.010). Conclusions: RIC regimen, grade Ⅱ-Ⅳ aGVHD and CMV-seropositive recipients are the main risk factors associated with CMV infection in PID patients post-UCBT. Survival rate of children with refractory CMV infection after UCBT is reduced. Immune reconstitution in children after UCBT should be regularly monitored, and frequency of CMV-DNA monitoring should be increased for children with delayed immune reconstitution.

P8.152: Clinical Characteristics and Factors Related to Recurrent Cytomegalovirus Infection Post-kidney Transplant in Adult Patients at Cho Ray Hospital

Introduction: Cytomegalovirus (CMV) is one of the main causes of opportunistic infections after kidney transplantation. Manifestations of CMV disease in post renal transplantation patients are quite discreet, non-specific and difficult to diagnose early. Asymptomatic recurrent CMV infection has been reported remarkably to increase mortality rate and rejection incidence, and effect on graft survival. The recently follow-up and treatment procedures’ changes make it urgent to re-evaluate the incidence and the factors related to the risk of CMV recurrence as well as the clinical characteristics of CMV infection in postkidney transplantation patients. This helps to control the recurrence of CMV infection as well as to diagnose CMV disease early and treat it promptly and appropriately to reduce the mortality rate of patients after transplantation. Method: Objective 1: Retrospective cohort study of adult renal transplant recipients between January 1, 2015 and December 31, 2018. Objective 2: A cross - sectional descriptive study on 22 cases of CMV disease in post kidney transplant patients to present a review of the main clinical aspects of cytomegalovirus infection in renal transplants with a focus on clinical approach and its future perspectives. Results: Objective 1: A total of 365 patients who received a renal transplant at Cho Ray hospital in the study time period were reviewed for the presence of CMV infection occurring less than 540 days after transplant. The recurrent CMV infection was observed in 254 cases (69,6%), but only 3 patients (0,8%) developed CMV disease. Independent risk factors of CMV infection were HLA >80 (HR = 2,309, 95% CI 1,021 – 4,071, p = 0,044), daily oral Prednisone doses used <0,5 mg/kg/day (HR = 0,178, 95% CI 0,084 – 0,374, p <0,001), Tacrolimus whole blood trough concentration ≤10 µg/L (HR = 0,445, 95% CI 0,243 – 0,816, p = 0,009), Cyclosporine wole blood trough concentration >150 µg/L (HR = 4,25, 95% CI 1,97 – 9,2, p < 0,001). Objective 2: Male majority (2/3), with average age of 47,5 ± 4,5. Rate of symptomic recurrence CMV infection in the first 6 months, 6 - 12 months, 1 - 5 years, 5 - 10 years after transplant were 45,4%, 9,1%, 27,3% and 18,2% respectively. Common clinical manifestations are fever 59,1%, respiratory, renal and gastrointestinal manifestations 31,8%, 27,3% and 13,6%, respectively. Two cases of CMV retinitis with typical fundus lesions were treated with intraocular Ganciclovir, however, vision was not fully recovered. Lymphopenia <1.000 cells/mm3 was observed in most cases of CMV disease after kidney transplantation. Quantitative PCR of CMV DNA in plasma ranged from 375 – 6.533.850 copies/mL. 6 of 22 cases of PCR CMV DNA in plasma >4.000 copies/mL, of which 5 severe cases developed rapidlly progressive respiratory failure and 2 deaths. Conclusion: Recurrent CMV infection has a high rate in adult patients after kidney transplantation, so it is necessary to take initiactive for screening, monitoring and treating early to reduce mortality and protect the transplanted kidney. The appropriate dose of immunosuppressants plays an important role in the prevention of recurrent CMV infection and the successful treatment of disease due to it. Key words: Cytomegalovirus, Kidney transplantation, Post-transplant infection. * Deparment of Tropical diseases– Cho Ray Hospital ** Nephrology Surgery – Cho Ray Hospital Coresponding author: Tho A. N. Vo, Deparment of Tropical diseases– Cho Ray Hospital. Email: [email protected]. Mobile: 0983888841.

424.1: Epidemiology of Cytomegalovirus Infection and Disease in Hematopoietic Stem Cell Transplant Recipients in Selected Countries Outside of North America and Europe: A Systematic Review

Background: Cytomegalovirus (CMV) is a highly prevalent herpes virus with a seroprevalence higher in South America, Africa, and Asia than in Europe and North America. In hematopoietic stem cell transplant recipients (HSCT), CMV infection is a common opportunistic infection and a major cause of morbidity and mortality. To better understand the epidemiology of CMV infection and disease post-HSCT in selected countries outside of Europe and North America, a systematic review was conducted. Methods: Observational studies that included HSCT recipients (any age) from 15 selected countries in Asia-Pacific, Latin America, Russia and the Middle East were considered (search period: 01 Jan. 2011 – 21 Jul. 2021). Outcomes of interest were incidence, recurrence rates and risk factors of CMV infection and CMV disease, and CMV-related mortality at any time point. Indexed publications (Ovid® MEDLINE and Embase, Cochrane Database of Systematic Reviews and World Health Organization database Global Index Medicus) were searched, supplemented by pragmatic searches of the grey literature and snowballing of references lists. The protocol was registered in PROSPERO (CRD42020205559). Results: A total of 63 studies (range: 33 to 10,206 patients), most conducted in adults (≥ 18 years; n=49 studies, 77.8%) and allogeneic HSCT recipients (n=53, 84.1%), were included in the review. In 43 of 54 studies reporting on incidence of CMV infection, within 1 year post-HSCT, estimates were uniformly distributed between 24.8% and 61.2% (Figure 1). Lower estimates were reported in autologous HSCT recipients (5.3%), and younger patients at the time of transplantation (9.3% in adults with a median age of 25 years and 18.6% in patients aged ≤20 years). Higher estimates (range: 69.4% to 88.2%) were found in 8 studies from China and South Korea, most with a follow-up period > 1 year (median: 27 to 54 months in 5 studies) (Figure 2). Incidence of CMV disease following HSCT was below 20%, with estimates uniformly distributed between 0% and 15.7% in allogeneic HSCT. According to 11 studies, reported rates of CMV recurrence ranged between 19.8% and 37.9%. Commonly reported risk factors for CMV infection or disease in HSCT recipients were high-risk CMV serostatus (R+) (hazard ratio [HR]: 2.6 and 3.7, odds ratio [OR]: 2.2 and 5.4), older age of recipients (HR for each additional year: 1.03-1.04), presence of acute or chronic graft versus host disease (HR: 1.1-2.5), haploidentical HSCT (HR: 2.7-6.4), and use of immunosuppressive agents (OR: 5.0-9.3). CMV-related mortality was reported in up to 10% of patients following HSCT (n=30 studies; period of assessment not reported). Conclusion: Relatively high rates of CMV infection, CMV disease and CMV recurrence were reported post-HSCT, with CMV-related mortality observed in up to 1 in every 10 patients. High rates of CMV infection and disease post-HSCT may impact graft outcomes and increase disease burden in patients post-transplantation.This review was funded by Takeda International AG – Singapore Branch. CMM has received honoraria from Takeda and MSD (advisory board, speaker, educational events, meeting). S-YC has served as a consultant for Takeda Pharmaceutical, and has received research support and payment for lectures from Merck Sharp & Dohme, Pfizer and Gilead. MS has received grants from F2G, Gilead, Merck and personal fees from Gilead, Pfizer, Takeda and Roche for work outside of this research; IS is an employee of Takeda Pharmaceuticals India Pvt Ltd. AS and DD are employees of Takeda International AG – Singapore Branch and hold stock options. WD has no conflicts of interest to disclose. Literature retrieval, analysis and medical writing support were provided by Aurore Bergamasco, Camille Goyer, and Yola Moride of YolaRX Consultants and funded by Takeda International AG – Singapore Branch.