CMV Infection In Patients Research Articles

Clinical and Economic Impact of CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation: Perspectives from a Middle-Income Nation.

Cytomegalovirus infection (CMV) is a common complication after allogeneic hematopoietic stem cell transplantation (AHSCT). CMV infection increases transplantation costs; however, the extent of the financial burden may vary in different countries. This study aims to determine the clinical and economic impact of CMV infection in patients undergoing AHSCT in a middle-income country. A total of 150 adult and pediatric patients post-AHSCT were included for analysis. In addition to incidence of CMV infections, data on graft versus host disease (GVHD) were also collected. Standard hospital charges for AHSCT and any additional transplantation-related expenditure within 12 months were also retrieved in 104 patients. CMV infection, acute GVHD and chronic GVHD occurred in 38.7%, 60.7%, and 22.0% of patients, respectively. Patients with CMV infections had higher readmission rates compared to those who did not (67.2%vs. 47.8%; p=0.020). Additional expenditure was seen in HLA-haploidentical AHSCT and CMV infection (MYR11 712.25/USD2 504.49; p<0.0001 and MYR5 807.24/USD1 241.79; p=0.036), respectively. This single-center study demonstrated that patients who underwent HLA-haploidentical AHSCT and subsequently developed CMV infection had higher transplantation expenditures compared to those who had matched-related transplantation. Further studies should be conducted to evaluate if primary prophylaxis against CMV is cost-effective, especially in patients who undergo HLA-haploidentical AHSCT.

Postnatal cytomegalovirus infection and pulmonary vascular disease in extremely premature infants: A case series.

Pulmonary vascular disease (PVD) is a major determinant of both morbidity and mortality in extremely low birth weight infants. It is biologically plausible that postnatal cytomegalovirus (pCMV) infection may lead to PVD in premature infants secondary to pneumonitis or via derangement of pulmonary vascular development directly through endothelial dysfunction. Uncertainty remains, however, regarding thresholds for intervention in premature infants with cardiorespiratory instability and presumed CMV infection likely secondary to the limited understanding of the natural history of the disease. We describe four cases of premature infants with clinical and echocardiography features of PVD, in the setting of postnatally acquired CMV. All patients had atypical PVD trajectories, refractory to vasodilator treatment, which improved after initiation of CMV treatment. We highlight the need to consider postnatally acquired CMV infection in patients with PVD non-responsive to standard pulmonary vasodilator therapies or disease severity which is out of proportion of the usual clinical trajectory. Treatment of extremely premature infants with CMV-associated PVD may have positive impact on cardiorespiratory health, although duration of therapy remains uncertain.

Dynamics of cytomegalovirus-specific T-cell recovery in allogeneic hematopoietic cell transplant recipients using a commercially available flow cytometry assay: A pilot study.

Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population. In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100. Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP. There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.

The Impact of Cytomegalovirus Infection on Natural Killer and CD8+ T Cell Phenotype in Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating neurological disease that has been classified as an immune-mediated attack on myelin, the protective sheath of nerves. Some aspects of its pathogenesis are still unclear; nevertheless, it is generally established that viral infections influence the course of the disease. Cytomegalovirus (CMV) is a major pathogen involved in alterations of the immune system, including the expansion of highly differentiated cytotoxic CD8+ T cells and the accumulation of adaptive natural killer (NK) cells expressing high levels of the NKG2C receptor. In this study, we evaluated the impact of latent CMV infection on MS patients through the characterization of peripheral NK cells, CD8+ T cells, and NKT-like cells using flow cytometry. We evaluated the associations between immune cell profiles and clinical features such as MS duration and MS progression, evaluated using the Expanded Disability Status Scale (EDSS). We showed that NK cells, CD8+ T cells, and NKT-like cells had an altered phenotype in CMV-infected MS patients and displayed high levels of the NKG2C receptor. Moreover, in MS patients, increased NKG2C expression levels were found to be associated with higher EDSS scores. Overall, these results support the hypothesis that CMV infection imprints the immune system by modifying the phenotype and receptor repertoire of NK and CD8+ T cells, suggesting a detrimental role of CMV on MS progression.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

T-lymphocyte subtyping: an early warning and a potential prognostic indicator of active cytomegalovirus infection in patients with sepsis.

Cytomegalovirus (CMV) infection is very common in patients suffering from sepsis and may cause poor prognosis. To explore the relationship between immune status of patients with sepsis and CMV infection, we assessed T lymphocyte subtyping and other commonly used clinical parameters in patients with sepsis upon admission to the intensive care unit (ICU) and evaluated their potential impact on diagnosis and outcomes of active CMV infection. In our study, 82 of 599 patients with sepsis were diagnosed with active CMV infection. The 28-day mortality was higher in active CMV-infected than nonactive CMV-infected patients (20.7% versus 9.9%); 51of 82 active CMV-infected patients with sepsis were assessed to have CMV-DNA-negative conversion, while 31 were persistently positive for CMV DNA. Higher CD8+ CD28+ T-cell counts at presentation were associated with CMV-DNA-negative conversion and lower 28-day mortality. The CMV-DNA-negative conversion and 28-day mortality of active CMV-infected patients with sepsis could be predicted using cutoff values of 151 (74.5% sensitivity and 87.1% specificity) and 64.5 (52.9% sensitivity and 92.3% specificity) CD8+ CD28+ T cells mL-1 at ICU admission, respectively. Higher CD8+ CD28+ T-cell count was significantly associated with active CMV infection, higher CMV-DNA-negative conversion and lower 28-day mortality, which may be a potential marker for early warning of active CMV infection and outcome prediction.

High Monocyte Count Associated with Human Cytomegalovirus Replication In Vivo and Glucocorticoid Therapy May Be a Hallmark of Disease.

Cytomegalovirus (CMV) syndrome and infectious disease are defined as pathogen detection with appropriate clinical symptoms, but there are not pathognomonic signs of CMV disease. Although the prodrome of acute minor viral infections leukopenia (lymphopenia and neutropenia) is noted with onset of fever, followed by monocytosis, the role of monocytosis in CMV disease has not been described. Furthermore, under influence of corticosteroid therapy, CMV reactivation and monocytosis are described, but without a strict relationship with steroids dose. In the study, the monocyte level was investigated during the CMV infectious process. Regrettably, a non-selected group of 160 patients with high CMV viremia showed high dispersion of monocyte level and comparable with the median value for healthy subjects. Therefore, we investigated monocyte level in CMV-infected patients in relation to the logarithmic phase of the infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. Significant monocytosis (above 1200/µL) during the logarithmic phase of CMV infection (with exponent between 3.23 and 5.77) was observed. Increased count and percentage of monocytes correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, glucocorticoids equivalent to 10 and 20 mg of dexamethasone during a 2–3-week period caused monocytosis—significant increase (to 1604 and 2214/µL, respectively). Conclusion: In light of the logarithmic increase of viral load, high monocytosis is a hallmark of CMV replication. In the COVID-19 era, presence of high virus level, especially part of virome (CMV) in the molecular technique, is not sufficient for the definition of either proven or probable CMV replication at any site. These preliminary observations merit additional studies to establish whether this clinical response is mediated by monocyte production or by decrease of differentiation to macrophages.

Cytomegalovirus Infection Associated with Smaller Total Cortical Surface Area in Schizophrenia Spectrum Disorders.

ObjectivesCytomegalovirus (CMV) congenital infection and in immunodeficiency can have deleterious effects on human cortex. In immunocompetent adults, the putative association between CMV infection and cortical measures has not been explored. We hypothesized that CMV exposure is associated with smaller cortical surface area or cortical thinning mainly in patients with schizophrenia spectrum disorders.Study DesignWe included 67 adult patients with schizophrenia spectrum disorders and 262 adult healthy controls. We measured circulating CMV IgG antibody concentrations with solid-phase immunoassay techniques. We measured the total cortical surface area, regional cortical surface areas and the overall mean cortical thickness based on T1-weighted MRI scans processed in FreeSurfer v6.0.Study ResultsIn the whole sample analysis, we found a significant diagnostic group-by-CMV status interaction on the total surface area (P = .020). Among patients, CMV antibody positivity was significantly associated with smaller total surface area (P = .002, partial eta2 = 0.138) whereas no such association was found in healthy controls (P = .059). Post hoc analysis among patients showed that higher CMV antibody concentrations were also significantly associated with smaller total surface area (P = .038), and that CMV antibody positivity was significantly inversely associated with 14 left and 16 right regional surface areas mainly in the frontal and temporal lobes. CMV infection was not associated with the overall mean cortical thickness.ConclusionsThe results are indicative of a cortical surface area vulnerability to CMV infection in patients with schizophrenia spectrum disorders but not in healthy controls. CMV infection may contribute to the established cortical surface area aberrations in schizophrenia.

Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients

Cytomegalovirus (CMV) infection is associated with graft rejection in renal transplantation. Memory-likenatural killer (NK) cells expressing NKG2C and lacking FcεRIγ are established during CMV infection. Additionally, CD8+ T cells expressing NKG2C have been observed in some CMV-seropositive patients. However, invivo kinetics detailing the development and differentiation of these lymphocyte subsets during CMV infection remain limited. Here, we interrogated the invivo kinetics of lymphocytes in CMV-infected renal transplant patients using longitudinal samples compared with those of nonviremic (NV) patients. Recipient CMV-seropositive (R+) patients had preexisting memory-like NK cells (NKG2C+CD57+FcεRIγ-) at baseline, which decreased in the periphery immediately after transplantation in both viremic and NV patients. We identified a subset of prememory-like NK cells (NKG2C+CD57+FcεRIγlow-dim) that increased during viremia in R+ viremic patients. These cells showed a higher cytotoxic profile than preexisting memory-like NK cells with transient up-regulation of FcεRIγ and Ki67 expression at the acute phase, with the subsequent accumulation of new memory-like NK cells at later phases of viremia. Furthermore, cytotoxic NKG2C+CD8+ T cells and γδ T cells significantly increased in viremic patients but not in NV patients. These three different cytotoxic cells combinatorially responded to viremia, showing a relatively early response in R+ viremic patients compared with recipient CMV-seronegative viremic patients. All viremic patients, except one, overcame viremia and did not experience graft rejection. These data provide insights into the invivo dynamics and interplay of cytotoxic lymphocytes responding to CMV viremia, which are potentially linked with control of CMV viremia to prevent graft rejection.

Cross-Reactive Results in Serological Tests for Borreliosis in Patients with Active Viral Infections.

Currently, serological tests for Lyme disease (LD), routinely performed in laboratories following the European Concerted Action on Lyme Borreliosis recommendations as part of two-stage diagnostics, are often difficult to interpret. This concerns both the generation of false positive and negative results, which frequently delay the correct diagnosis and implementation of appropriate treatment. The above problems result from both morphological and antigenic variability characteristics for the life strategy of the spirochete Borrelia burgdorferi sensu lato, a complicated immune response, and imperfections in diagnostic methods. The study aimed to check the reactivity of sera from 69 patients with confirmed infection with Epstein–Barr virus (EBV), cytomegalovirus (CMV) and BK virus (BKV) with Borrelia antigens used in serological tests: indirect immunofluorescence (IIFT), enzyme-linked immunosorbent (ELISA) and immunoblot (IB). In the group of patients infected with EBV, the highest percentage of positive/borderline anti-Borrelia IgM and IgG results was obtained in the following tests: IIFT (51.9% for IgM, 63.0% for IgG), ELISA (22.2% for IgM, 29.6% for IgG) and IB (11.1% for IgM, 7.4% for IgG). In the group of CMV-infected patients, the highest percentage of positive/borderline anti-Borrelia IgM results were obtained in the following tests: IB (23.1%), IIFT (15.4%) and ELISA (7.7%), while in the IgG class in the IIFT (15.4%), IB (11.5%) and ELISA (3.9%) tests. In the group of patients infected with BKV, the highest percentage of positive/borderline anti-Borrelia IgM results was obtained in the following tests: IIFT (25.0%), IB (25.0%) and ELISA (3.9%), and in the IgG class in the tests: IB (50.0%), IIFT (6.2%) and ELISA (6.2%). The native flagellin (p41) and OspC proteins were the most frequently detected Borrelia antigens in all studied groups of patients in both classes of antibodies. Similar to other authors, the study confirmed the fact that serological tests used in the diagnosis of LD have a high potential to generate false positive results in patients with active viral infections, which may be related to cross-reacting antibodies appearing during the most common polyclonal activation of T/B lymphocytes, activated by viral superantigens.

Cytomegalovirus infection among patients with cancer receiving immune checkpoint inhibitors.

BackgroundImmune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients.MethodsWe conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records.ResultsThe study population comprised 192 patients overall. CMV infection incidence was 7.7% in ICI patients and 12.9% in non-ICI patients (P<0.001). Rates of infection clearance (83% vs. 50%, P=0.002) and recurrence (20% vs. 3%, P=0.037) were higher in ICI patients with hematologic vs. solid tumors, despite similar treatments. All-cause mortality was higher in solid rather than hematologic malignancies in ICI patients (83% vs. 54%, P=0.009); CMV-related mortality was low (3-4%) in both groups.ConclusionsCMV infection occurred in about 7.7% of the ICI-treated cancer population. The infection can be disseminated in multiple organs and has a wide spectrum of clinical symptoms. ICI-treated patients with a hematologic malignancy had higher viral clearance and recurrence than those with solid tumors. In this study, CMV itself did not lead to high mortality in cancer patients. Further study is needed to investigate the role of CMV infection in patients’ irAEs and cancer outcome.

Clinical Use of CMV-Specific T Cells Derived from CMV-Naïve Donors

▪Background: Adoptive Immunotherapy with virus-specific T cells (VST) derived from hematopoietic stem cell (HSC) donors has been highly successful in preventing or treating CMV and other viruses in previous trials, but previously, VST could not be produced from adult virus-naïve donors. While “off the shelf” third party VSTs can offer a short term therapeutic approach for these patients, third party donor VSTs do not contribute to long term virus-specific immune reconstitution in these patients. Hence, we developed a novel approach to manufacture CMV-specific VST from CMV-naïve donors utilizing CD45RA selection and serial stimulation with virus peptide pulsed antigen presenting cells.Objective: To determine if VST derived from CMV-naïve donors are safe and effective in preventing or treating CMV infection in patients following hematopoietic stem cell transplantation.Methods: VST were produced from peripheral blood of CMV-naïve HSC donors. CMV-specific T-cells were produced via immunomagnetic selection of CD45RA+ cells, which were stimulated with dendritic cells pulsed with 15-mer peptide pools encompassing CMV antigens pp65 and IE1. VST were stimulated twice more over 3 weeks with EBV-lymphoblastoid cells pulsed with CMV peptides. EBV and adenovirus-specific VST were produced from the same donors in a separate culture with a single stimulation of peripheral blood mononuclear cells with peptide pools encompassing the EBV antigens EBNA1 and LMP2 and the adenovirus antigens hexon and penton. Recipients received CMV-specific and EBV/adenovirus-specific VST as a combined infusion at or after day +28 post HSCT. VST expansion following infusion was measured via Interferon-g ELISpot from peripheral blood and TCRV-beta sequencing.Results: Four clinical CMV-specific products have been produced to date from CMV-naïve adult donors, and 3 patients have been treated with a median follow-up time of 2 months. All patients received a single VST infusion at a dose of 5x10E6/m2, split equally between the CMV and EBV/adenovirus-specific components. All patients tolerated the infusions well with no toxicities or graft versus host disease. Two of the patients were treated prophylactically, and remain free of CMV, EBV, and adenovirus. One patient was treated for existing CMV reactivation. In the patient with CMV reactivation, activity against CMV-pp65 and IE1 initially fell, then rose and stabilized after infusion (IE1 Spot forming cells (SFC), range: 10-42; pp65 SFC: 16-159). CMV viral level remained detectable at low levels only (110-308 IU/ml), and the patient never developed viral disease.Conclusions: CMV-specific VST derived from CMV-naïve donors appear to be safe, and may be clinically efficacious in vivo and offer a solution to enhance long term immune reconstitution to CMV in high risk patients after HSCT. DisclosuresBollard:Torque: Membership on an entity's Board of Directors or advisory committees; Neximmune: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellectis: Membership on an entity's Board of Directors or advisory committees.

Post-Liver Transplant Cytomegalovirus (CMV) Reactivation, Graft, and Patient Survival Rates in Iranian Population

Background: Human cytomegalovirus (CMV) is the major complication of viral infection in immunocompromised patients. This opportunistic infection is associated with high morbidity and mortality in transplanted recipients. Objectives: The present study aimed to determine CMV burden and assess the clinical outcome in the liver recipients with CMV reactivated infection at Nemazi Hospital, Shiraz, Iran. Methods: This retrospective study examined 657 patients who underwent liver transplantation during 2014 - 2017 to identify the CMV infection, morbidity, and mortality rates. To this end, the medical records of such patients were reviewed, and their rejection/survival rates were analyzed. Accordingly, the CMV infection was diagnosed by Taq-Man real-time PCR assays. Results: In this study, 151 (23%) had CMV reactivation at least one year after liver transplantation. Viremic patients had a viral burden between 300 - 738790 copies/mL. In this study, 41 persons (6.2%) died, and 58 liver transplant patients (8.8%) had rejection experience up to one year after their operation. Among the 41 dead patients, 21 and 20 cases were with and without CMV-reactivation, respectively. The results demonstrated that the mortality rate was significantly higher in the CMV-infected patients than the non-CMV-infected counterparts. In contrast, the graft survival rate was not significantly different between the two groups (P ≤ 0.05). Conclusions: In the present study, CMV infection can serve as a significant mortality predictor in LT patients.

Abdominal aortic aneurysm and virus infection: A potential causative role for cytomegalovirus infection?

An abdominal aortic aneurysm (AAA) is a multifactorial disease with a variety of genetic and environmental risk factors, but the exact mechanism of AAA formation and progression is still not well understood. The present study investigated the frequency of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and papillomavirus types 6 and 11 (HPV6 and HPV11), their impact on clinical manifestations of cardiovascular diseases, and their possible association with inflammation in patients with AAA and healthy volunteers. Genotyping of CMV UL75, EBV LMP-1, and HPV6 and HPV11 E6 was performed by polymerase chain reaction (PCR), while the viral DNA loads were measured by quantitative real-time PCR (qRT-PCR). Cytokine levels were determined by enzyme-linked immunosorbent assays (ELISAs). The CMV UL75 was detected more frequently in the blood of patients with AAA than in the blood of healthy volunteers (32.7% vs. 6.3%, p < 0.0001). Neither EBV LMP-1 nor HPV6 E6 was found in blood and aortic wall biopsies, while the HPV11 E6 was detected in 36.4% of AAA walls. The CMV infection in patients with AAA was associated with an increased risk of hypertension and coronary artery disease (CAD) (OR 9.057; 95% CI: 1.141 - 71.862, p = 0.037; OR 2.575; 95% CI: 1.002 - 6.615, p = 0.049, respectively). Additionally, CMV-infected patients with AAA had higher TNF-α levels compared with non-infected subjects (p = 0.017). Our findings suggest that CMV infection can stimulate local inflammation in the aorta but is not a direct cause of most abdominal aortic aneurysms. This article is protected by copyright. All rights reserved.

Polymorphisms of the cytomegalovirus glycoprotein B genotype in patients with Posner-Schlossman syndrome

AimsThe aim of this observational study was to report the distribution of glycoprotein B (gB) genotypes in the eyes of cytomegalovirus (CMV) positive patients with Posner-Schlossman syndrome (PSS), and to...

Clinical Features and Risk Factors of Systemic Lupus Erythematosus Complicated with Cytomegalovirus Infection

Objective To explore the clinical characteristics and risk factors of systemic lupus erythematosus(SLE)complicated with cytomegalovirus infection(CMV). Methods The medical records of patients diagnosed with SLE at discharge in the Department of Immunology at Peking Union Medical College Hospital between July 1,2017 and April 1,2019 were retrospectively reviewed,and the clinical and laboratory data related to CMV infection were analyzed. Results Of the 231 patients with SLE,115(49.8%)had CMV infection.Among them,78(67.8%)were asymptomatic CMV infection and 37(32.2%)were diagnosed with CMV disease.Univariate analysis showed the number of organs involved(P=0.015),presence of other infections(P=0.004),methylprednisolone pulse therapy(P=0.001),cumulative dose of prednisolone within 30 days(P=0.001),average dose of prednisolone within 30 days(P<0.001),intravenous cyclophosphamide(P=0.003),methylprednisolone pulse therapy plus immunosuppressants(P=0.001),Systemic Lupus Erythematosus Disease Activity Index 2000 at admission(P=0.018),and serum albumin(ALB)level≤30 g/L(P<0.001)were associated with CMV infection.Multivariate analysis showed presence of other infections(OR=8.003,95%CI=2.108-30.383,P=0.002),methylprednisolone pulse therapy plus immunosuppressants(OR=10.336,95%CI=2.107-50.711, P=0.004),and serum ALB≤ 30 g/L(OR=3.367,95%CI=1.157-9.796,P=0.026)were independent risk factors for CMV infection. Conclusion Presence of other infections,recent methylprednisolone pulse therapy plus immunosuppressants,and serum ALB≤30 g/L can increase the risk of CMV infection in patients with SLE.

A study on the seroprevalence of cytomegalovirus infection in patients with coronary artery disease in a tertiary care hospital

Introduction: Coronary artery disease (CAD) is a leading cause of death in developing and developed countries. Infectious etiology is also suspected to be a significant risk factor in these cases. CMV is a beta herpes virus. Once infected, the person carries the virus for life.80% adults show CMV specific antibodies in their serum indicating the high prevalence of CMV infection. Aim: To know the seroprevalence of CMV infection in patients with CAD Materials and Methods: Clinically stable patients undergoing coronary angiography because of symptoms suspected of CAD were included in the study. The samples were tested for specific anti-CMV IgG antibodies by ELISA Results: Of 150 patients, 86 % had detectable quantities of anti-CMV IgG antibodies in their serum. 15 patients (10%) were found to be ‘borderline positive,’ and the antibody index was between 0.9 to 1.1. 6 patients (4%) did not have detectable quantities of anti-CMV IgG antibodies in their serum. Prevalence of CAD was 100% in the study group. Conclusion: Cytomegalovirus is an essential cause of atherosclerosis due to the infectious burden. In the study population, 86% of the patients showed elevated levels of anti-CMV IgG antibody. So, there is an association between CMV infection and coronary artery disease. Keywords: Coronary artery diseases, Cytomegalovirus, Infection.

Use of letermovir in off-label indications: Infectious Diseases Working Party of European Society of Blood and Marrow Transplantation retrospective study

Letermovir (LMV) is licensed for prophylaxis of CMV infection in allogeneic hematopoietic cell transplant adult CMV-seropositive patients. Due to its favorable safety profile, LMV brings potential for use in other clinical situations, outside the approved indication. The objective of the study was to analyze the efficacy and safety of the use of LMV in off-label indications in EBMT centers. A total of 49 patients were reported including 44 adults and 5 children. LMV was administered for: secondary prophylaxis (37 adults, 3 children), primary prophylaxis (2 children), pre-emptive treatment (5 adults), and therapy of CMV disease (2 adults; pneumonia, colitis). Cyclosporine was concomitantly used in 26 patients. Overall, LMV was used for a median 112 days (range: 10-473). Cumulative incidence of breakthrough infections during secondary prophylaxis was 10.1% (95% CI = 3.1-21.9). Prophylactic treatment with LMV resulted in 94.9% (95% CI = 81.0-98.7), and 81.9% (95% CI = 65.7-90.9) probability of, respectively, 60 and 120-day survival without CMV infection in patients receiving secondary prophylaxis. During therapy of CMV infection/disease, probability of 60 and 120-day overall survival was 100% and 71.4% (95% CI = 25.8-92.0), respectively. No breakthrough infection occurred in children on LMV prophylaxis. Adverse events were reported in 15/49 (30.4%) patients: the most common being nausea/vomiting (22.4%). In conclusion, the efficacy of the use of LMV as secondary prophylaxis was high, and the preliminary experience with the use of LMV for the treatment of patients with refractory CMV infection/disease was positive. Our data showed that higher dose or prolonged therapy did not result in increased rate of adverse events.

IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis

BackgroundCytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients.MethodsA total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses.ResultsA total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49–73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05–119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively.ConclusionsHigh-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.

Genetic and Functional Characterization of Toll-Like Receptor Responses in Immunocompetent Patients With CMV Mononucleosis.

Background: Human cytomegalovirus (CMV) modulates both innate and adaptive immune responses. However, limited data are available on the role of receptors of innate immunity, such as toll-like receptors (TLRs) in contributing to antiviral responses and inflammation.Objectives: The aim of this translational study was to characterize TLR responses in immunocompetent patients with primary and symptomatic CMV infection.Study Design: The study population consisted of 40 patients suffering from CMV mononucleosis and 124 blood donors included as controls. We evaluated the association between TLR2, 3, 4, 7 and 9 gene single nucleotide polymorphism (SNP) and susceptibility to symptomatic CMV infection in immunocompetent adults. Additionally, functional TLR-mediated cytokine responses in supernatants of short-term cultures of whole blood from patients with CMV mononucleosis and blood donors were evaluated.Results: TLR2 and TLR7/8 responses were altered in CMV infected patients as compared to healthy donors and were associated with the release of higher levels of the pro-inflammatory cytokines IL-6 and TNF-α, but not of the anti-inflammatory mediator IL-10. The analysis on the TLR SNPs indicated no difference between patients with CMV infection and the control group.Conclusions: No variation in the TLR2,3,4,7 and 9 genes was associated to the development of symptomatic CMV infection in immunocompetent adults. Nevertheless, TLR-mediated responses in CMV-infected patients appeared to be skewed toward a pro-inflammatory profile, which may contribute to the development of inflammatory symptoms during the CMV mononucleotic syndrome.