Cytomegalovirus Infection In Patients Research Articles

Risk factors and outcomes of cytomegalovirus infection in the intensive care unit.

Cytomegalovirus (CMV) infection has long been recognized as an important viral syndrome in the immunocompromised host. The disease is less well described in critically-ill patients. We evaluated the risk factors for the development of CMV infection in patients admitted to the intensive care unit (ICU). We also compared the outcomes of CMV infection in ICU patients to those of patients with hematological malignancies. This is a retrospective study composed of three arms: patients admitted to the ICU with infection (ICU + / CMV + arm), patients admitted to the ICU who did not develop CMV infection (ICU + / CMV- arm, and patients with hematological malignancies on the hematology ward without CMV infection (ICU - / CMV + arm). Patients who were admitted to ICU for surgical causes had a decreased risk of CMV infection. On the other hand, receiving corticosteroids and vasoactive drugs was associated with an increased risk of CMV infection with adjusted odds ratios (aOR) of 2.4 and 25.3, respectively. Mortality was higher in ICU + / CMV + patients compared to ICU - / CMV + patients. In the ICU + /CMV + population, male sex and being on mechanical ventilation after CMV infection were independent predictors of mortality (aOR 4.6 and 5.0, respectively). CMV infection in ICU patients is a potentially serious disease requiring close attention. The findings from our study help in identifying patients in the ICU at risk for CMV infection, thereby warranting frequent screening. Patients at high risk of death (male, on mechanical ventilation) should receive prompt treatment and intensive follow-up.

Considerable differences in management of cytomegalovirus infection in patients with biliary atresia

AbstractObjectivesPatients with biliary atresia (BA) and ongoing cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy than uninfected patients. Still, there is no consensus on the usefulness of viral testing and antiviral treatment (AVT). This study aims to explore the need for future research on AVT for CMV infection by assessing how CMV infection in BA patients is managed in different centers.MethodsAn online questionnaire with 10 questions was offered to participants at an international congress on BA, organized in collaboration with the European Reference Network (ERN) for rare liver diseases in 2022. Answers to questions were either dichotomic or multiple choices of different numeric intervals. Ongoing CMV infection was defined by detecting CMV‐IgM in serum or CMV‐DNA by PCR in blood or urine.ResultsThere were 43 respondents from 36 centers in 26 countries. The total number of BA patients per year was between 208 and 380 from centers with 0–5 to >20 BA patients yearly (median 6–10). CMV infection was tested in 27 centers (75%), of which 18 (67%) use AVT. The rate of CMV infection varied between 0%–5% and 40%–50% (median 5%–10%). Willingness to treat the infection did not differ between centers with low and high rates of CMV infection.ConclusionsMost centers test for CMV infection, and a considerable proportion use AVT despite the lack of evidence of its benefits. A future randomized study on treating CMV infection in BA patients is necessary and feasible.

Clinical features and prognosis of systemic lupus erythematosus complicated by active cytomegalovirus infection: a retrospective cohort study.

The aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection. This retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months. A total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = -0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871-10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071-4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563-7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621-396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029-3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190-27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074-10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months. In SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months.

High-Dose Intravenous Immunoglobulin to Treat Anti-Thymocyte Globulin Induction–Related BK Virus and Cytomegalovirus Infection in Patients with ABO-Incompatible Kidney Transplantation

ABO-incompatible (ABOi) transplantation is a novel method transplantation method that carries a heightened risk of infection caused by the use of high immunosuppressant doses. This elevated risk is particularly concerning for viral infections, such as cytomegalovirus (CMV) and the BK virus (BKV) increases. Herein, we present a case where high-dose intravenous immunoglobulin (IVIG) was effective in treating viral infections after transplantation. A 41-year-old man underwent an ABOi transplantation. The initial isoagglutinin titer was 1:32. The patient received 200 mg of rituximab, and 3 rounds of plasmapheresis were performed. Subsequently, renal function remained normal; however, 7 months later, the renal function declined, and BK nephropathy and CMV infection were diagnosed through biopsy and serologic tests. The FK level was reduced, and mycophenolate mofetil was discontinued. Although ciprofloxacin and leflunomide were administered, their effects were minimal. Therefore, high-dose IVIG (1 g/kg) was administered 5 times over 5 weeks, which led to a reduction in BK viral load and CMV infectivity in the serum. High-dose IVIG may serve as a promising alternative treatment to mitigate early transplant rejection and BKV and 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.

Reply to: "Cytomegalovirus infection in patients with biliary atresia-further questions and possible solutions".

Reply to: "Cytomegalovirus infection in patients with biliary atresia-further questions and possible solutions".

Cytomegalovirus infection in patients with biliary atresia-further questions and possible solutions.

Cytomegalovirus infection in patients with biliary atresia-further questions and possible solutions.

Letermovir Effectively Prevents Cytomegalovirus Infection in Patients with Aplastic Anemia After Hematopoietic Stem Cell Transplantation: A Real-World Retrospective Cohort Study.

In this single-center retrospective cohort study, we investigated the efficacy of letermovir in preventing Cytomegalovirus (CMV) infection in patients with aplastic anemia (AA) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Based on whether or not letermovir was used for preventing CMV infection, the patients were categorized into two groups: letermovir and control groups. The overall survival (OS) rate and cumulative incidence of CMV infection during the first 100days after allo-HSCT were evaluated. The study included 21 matched pairs of patients, identified through propensity score matching analysis, to compare CMV infection rates, treatment efficacy, and regression. The incidence of CMV infection within 100days after transplantation was significantly lower in the letermovir group than in the control group (26.5 vs. 77.4%, respectively; P < 0.001), among a total of 87 patients who underwent the transplant. In the matched cohort of 21 patients with AA, the letermovir group also showed a significantly reduced cumulative incidence of CMV infection (14.3 vs. 90.5% in the control group; P < 0.001). Compared to the control group, patients with CMV infection in the letermovir group had lower CMV-DNA load and a shorter clearance time. However, there was no significant difference in OS between both groups (P = 0.34). Letermovir effectively prevents CMV infection in allo-HSCT recipients with AA and demonstrates a high safety profile.

P1218 Non-invasive point-of-care stool sample for detection of Cytomegalovirus infection in patients with Active or Refractory Ulcerative Colitis using multiplex polymerase chain reaction (mPCR): a pilot feasibility study

Abstract Background Cytomegalovirus (CMV) infection is associated with more flare-ups and deteriorates the prognosis of active inflammatory bowel disease (IBD). Patients with refractory IBD should be tested for CMV colitis, especially if they are not responding to immunosuppressive therapy. The prevalence of CMV co-infection ranges from 10% to 30% in steroid-refractory acute colitis. Concurrent CMV-colitis is associated with an increased risk of worse therapeutic outcomes, resistance to corticosteroids, and need for salvage therapy. One of the two gold standards of diagnosis of CMV colitis in IBD patients with active disease requires the analysis of tissue biopsies using PCR. The aim of our pilot study was to evaluate the diagnostic accuracy of non-invasive point-of-care faecal samples using mPCR for detecting CMV in patients with ulcerative colitis compared to standard practice biopsies PCR. Methods We performed a prospective, observational, feasibility study including 62 consecutive patients with active ulcerative colitis (UC) requiring intravenous steroids or steroid-refractory UC in the Department of Gastroenterology of University Hospital „Tsaritsa Yoanna – ISUL", from April 2022 to October 2023. In all UC patients, colonic tissue biopsies were performed and analyzed by qualitative CMV PCR. Faecal sample mPCR CMV was performed on the positive patient cohort to compare the feasibility of (ME) Panel IVD using FilmArray mPCR (Biofire, bioMerieux, France). All the tested patients had undergone immunosuppressive therapy and initial stool specimen cultures were obtained to exclude infection with C. difficile and other pathogen flora. Results Out of 62 active UC patients with colonic tissue samples qualitative CMV PCR, n=5 (8%) were positive. Of these n=5 UC patients, n=4 (80%) were positive from the Fecal sample mPCR CMV, resulting in a compatibility of 80% for diagnosing CMV in these patients by the two DNA extraction methods. Calculated Sensitivity and diagnostic accuracy was 80% (95% CI) for the mPCR CMV. The patient cohort predominantly comprised males (75%) with a median age of 45 years (range: 30–72 years). Three patients (75%) out of this cohort group were treated with peroral antiviral agent Valganciclovir, one (25%) of them went into clinical and endoscopic remission after the treatment and two patients (50%) received colectomy. The median time performing the Faecal sample mPCR CMV was approx. 1 hour. Conclusion This novel faecal mPCR point-of-care test is a promising, fast and easy non-invasive tool for detection CMV in active or refractory UC patients, comparable with the colonic tissue CMV-DNA PCR.

Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

In a pivotal phase 3 trial of cytomegalovirus prophylaxis with letermovir for up to 100 days after allogeneic haematopoietic stem-cell transplantation (HSCT), 12% of participants developed clinically significant cytomegalovirus infection after letermovir was discontinued. We aimed to evaluate the efficacy and safety of extending the duration of letermovir prophylaxis for clinically significant cytomegalovirus infection from 100 days to 200 days following HSCT. We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 32 sites in six countries (France, Germany, Italy, Japan, the UK, and the USA). Cytomegalovirus‑seropositive HSCT recipients (aged ≥18 years) who had received letermovir prophylaxis for up to 100 days following HSCT and who remained at high risk of late clinically significant cytomegalovirus infection (with no previous history of clinically significant cytomegalovirus infection, defined as initiation of pre-emptive therapy for documented cytomegalovirus viraemia, onset of cytomegalovirus end-organ disease, or both) were eligible. Participants were randomly assigned (2:1) to receive either an additional 100 days (ie, a total of 200 days; letermovir group) of oral or intravenous letermovir 480 mg once daily, adjusted to 240 mg once daily for participants on cyclosporin A, or 100 days of a placebo comparator for letermovir (ie, a total of 100 days of letermovir; placebo group), following HSCT. Randomisation was done using a central interactive response technology system, stratified by study centre and haploidentical donor (yes or no). Participants, investigators, and sponsor personnel were masked to the treatment allocation. The primary efficacy endpoint was the proportion of participants from randomisation to week 28 (200 days after HSCT) with clinically significant cytomegalovirus infection, analysed using the full analysis set population (ie, those who received at least one dose of study intervention). Safety was analysed in all participants as treated (ie, those who received at least one dose according to the study intervention they were assigned to). This study is registered with ClinicalTrials.gov, NCT03930615, and is complete. Between June 21, 2019, and March 16, 2022, 255 patients were screened for eligibility and 220 (86%) were randomly assigned (145 [66%] in the letermovir group and 75 [34%] in the placebo group). Between randomisation and week 28, four (3%) of 144 participants in the letermovir group and 14 (19%) of 74 in the placebo group developed clinically significant cytomegalovirus infection (treatment difference -16·1% [95% CI -25·8 to -6·5]; p=0·0005). The most common adverse events among participants in the letermovir group versus the placebo group were graft-versus-host disease (43 [30%] vs 23 [31%]), diarrhoea (17 [12%] vs nine [12%]), nausea (16 [11%] vs 13 [18%]), pyrexia (13 [9%] vs nine [12%]), and decreased appetite (six [4%] vs nine [12%]). The most frequently reported serious adverse events were recurrent acute myeloid leukaemia (six [4%] vs none) and pneumonia (three [2%] vs two [3%]). No deaths were considered to be drug-related by the investigator. Extending the duration of letermovir prophylaxis to 200 days following HSCT is efficacious and safe in reducing the incidence of late clinically significant cytomegalovirus infection in patients at risk. Merck Sharp & Dohme LLC.

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

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

Tissue quantitative RT-PCR test for diagnostic significance of cytomegalovirus infection in patients with inflammatory bowel disease and treatment response: Cytomegalovirus infection in patients with inflammatory bowel disease.

Cytomegalovirus (CMV) is an opportunistic pathogen that exacerbates inflammatory bowel disease (IBD). There are no clear diagnostic criteria for CMV infection in IBD patients. The aim of this study was to evaluate the importance of the diagnosis of CMV infection with CMV-DNA polymerase chain reaction (PCR) in the colonic mucosa and the response to antiviral treatment. We retrospectively analyzed the clinical data of 30 patients with IBD (24 men, 6 women; median age: 42 years) who were hospitalized because of IBD exacerbation and whose samples were assessed by tissue CMV-DNA PCR positivity. Most of the IBD patients had ulcerative colitis (90%). The CMV-DNA PCR median value was 8848 copies/mL of tissue (range 90-242,936 copies/mL). Blood CMV-DNA PCR was found to be positive in a small group (33.3%, 10/30) of tissue CMV-DNA PCR-positive cases. immunohistochemistry tests were positive in only 5 of the 23 patients positive for CMV-DNA PCR in the colonic mucosa, and high remission (25/30, 83.3%) was detected with antiviral therapy. Recurrence of CMV colitis infection was observed in 9 of 25 patients who had remission with antiviral therapy. The tissue CMV-DNA PCR test was found to be more useful than blood CMV-DNA PCR and immunohistochemistry tests for diagnosing CMV colitis, and the tissue CMV-DNA PCR test enabled rapid and appropriate treatment.

Importance of using tissue PCR to diagnose CMV colitis in ulcerative colitis

Objective: To show the importance of tissue Cytomegalovirus (CMV) PCR to diagnose CMV infection in patients with treatment-resistant ulcerative colitis.&#x0D; Methods: Fifteen patients who had previously been diagnosed as ulcerative colitis with clinical, endoscopic, histological, and radiological criteria and who had referred to our clinic with acute exacerbation who were diagnosed with CMV colitis and received CMV treatment, were evaluated retrospectively. After the demographic and clinical characteristics of the patients were noted, Mayo scores were evaluated to determine ulcerative colitis activity. Patients' age, gender, laboratory values, type of colitis, and Mayo scores were recorded. Biopsy results, CMV IgM, serum, and tissue CMV DNA levels were noted. Descriptive statistical parameters of the demographical data were calculated.&#x0D; Results: Eleven of the patients were male, and four were female. The mean age of the patients was 42±11,3. The mean duration of the disease was 28±46 months. Twelve patients had pancolitis, and three patients had distal colitis. All patients' Mayo score was 12 points. All patients were steroid-resistant, and none had previously received biological agent therapy. 7 of 15 patients had serum CMV DNA levels over 1000 copies/mL. Tissue CMV DNA levels of 8 patients were found higher than 250 copies/mg, although serum CMV DNA levels were below 1000 copies/mL. Pathology samples of 11 patients were evaluated, and CMV inclusion bodies were not detected. All patients received ganciclovir for CMV treatment. After treatment, CMV DNA of all patients was negative, and diarrhea and inflammation markers were reduced.&#x0D; Conclusion: For the diagnosis of CMV, CMV-PCR in colon tissue specimens should also be considered in addition to endoscopic appearance and serum CMV DNA levels.

Cytomegalovirus Infections in Patients Treated With Immune Checkpoint Inhibitors for Solid Malignancies.

Cytomegalovirus (CMV) infection/disease has been repeatedly reported in patients treated with immune-checkpoint inhibitors (ICIs) and most commonly involves patients with relapsed/refractory (R/R) immune-related adverse events (irAEs). In the current study, we present a patient with melanoma who developed CMV gastritis during treatment with pembrolizumab in the absence of irAEs and without previous or current immunosuppression. Moreover, we review the literature regarding CMV infection/disease in patients treated with ICIs for solid malignancies. We present the currently available data on the pathogenesis, clinical characteristics, endoscopic findings, and histologic features and highlight the potential differences among cases complicating R/R irAEs versus those occurring in patients who are immunosuppression naive. Finally, we discuss the currently available data regarding potential useful diagnostic tools as well as the management of these patients.

Cytomegalovirus infection associated with smaller cerebellum in severe mental illness

IntroductionPostnatal cytomegalovirus (CMV) infection of immunocompetent hosts is usually inapparent but typically results in lifelong latency. Congenital CMV infections as well as CMV infections in patients with immunodeficiencies have been linked to major cerebellar pathology. Patients with severe mental illness have been repeatedly found to have smaller cerebellum, and they may be particularly susceptible to CMV infections. Finally, both animal and human studies have shown a differential male and female immune response to CMV.ObjectivesWe evaluated whole cerebellar grey matter volumes (CGMV) in CMV immunoglobulin G (IgG) seropositive (CMV+) and seronegative (CMV-) patients with severe mental illness and healthy controls (HC). We hypothesized that CMV seropositivity, reflecting previous infection and current latency, is associated with smaller CGMV in patients but not in HC, and that such a putative association may be sex-dependent.MethodsWe included 529 adult patients with severe mental illness (CMV+ 57%, women 48%), i.e., 324 patients with schizophrenia spectrum disorders and 205 patients with bipolar spectrum disorders, and 494 HC (CMV+ 56%, women 45%). MRI scans were obtained with a 1.5T Siemens scanner (n=596) and two 3.0T General Electric scanners (n=427), and processed with FreeSurfer v6.0. Circulating CMV IgG concentrations were measured with immunoassays. In age-, scanner- and estimated total intracranial volume-adjusted analyses of covariance (ANCOVAs), we investigated main and interaction effects of CMV status and sex on CGMV in patients and HC.ResultsCMV+ patients had smaller CGMV than CMV- patients (p=0.042). There was no CGMV difference between CMV+ and CMV- HC (p=0.858). The adjusted CGMV means in CMV+ patients and CMV- patients were 115078 mm3 and 116725 mm3, respectively (p=0.042); the adjusted CGMV means in CMV+ and CMV- HC were 117980 mm3 and 117840 mm3, respectively (p=0.858) (Image). Among patients, a trend towards CMV-by-sex interaction (p=0.073) was found. Post-hoc analyses showed a significant CMV-CGMV association in the female patient group (p=0.005), with no association among male patients (p=0.840).Image:ConclusionsCMV IgG seropositivity is associated with smaller cerebellum in severe mental illness, an effect driven by the female patients, but not among HC. This may indicate a CMV-related deleterious impact on cerebellum restricted to patients.Disclosure of InterestNone Declared

COVID-19 in patients with HIV: case-series

The article presents a series of clinical observations of confirmed cases of COVID-19 in hospitalized adult patients with HIV infection. The observed group of patients was characterized by a young age, a different spectrum of comorbid pathology, a moderate and comparable clinical and laboratory course, with the exception of a more prolonged clearance of SARS-CoV-2 compared with COVID-19 patients from the general population. Advanced stage of HIV infection with the development of secondary diseases (p=0.08), decrease in the relative number of CD4+T-lymphocytes less than 2% (p=0.03), and CD4+/CD8+ less than 0.05 (p=0.03), the presence of cytomegalovirus infection (p=0.004) distinguished HIV-SARS-CoV-2-coinfected patients with poor outcomes. The presence and similarity of the clinical and radiological course of COVID-19 and cytomegalovirus infection in patients with severe immunodeficiency was noted, which requires an extremely thorough differential diagnosis.

Reactivación de citomegalovirus en pacientes con gastritis inmunomediada

IntroductionReactivation of cytomegalovirus can complicate the evolution of patients with gastritis induced by immune checkpoint inhibitors. MethodsThe experience in our center is described and a review of the literature is performed. ResultsA case of severe gastritis induced by treatment with a programmed cell death receptor-1 (anti-PD1) inhibitor, associated with reactivation of cytomegalovirus (CMV) is described. In the systematic review, we identified 5 cases of immune-related gastritis associated with CMV reactivation. Ganciclovir treatment contributed to clinical improvement in most patients. ConclusionThe early identification of a CMV infection in patients with severe or refractory immune-related gastritis will allow the initiation of targeted treatment, and may avoid increasing immunosuppressive therapy.

Evaluation of Platelet Parameters in Patients With Secondary Failure of Platelet Recovery and Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation.

To investigate the clinical significance of changes in platelet parameters in patients with secondary failure of platelet recovery (SFPR) and cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). In this retrospective study, 79 patients who had undergone allogeneic HSCT (allo-HSCT), including 40 patients with SFPR and 39 patients without SFPR, were recruited. The evaluated parameters were platelet count (PLT), plateletcrit (PCT), platelet-large cell ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), the incidence of CMV infection after allo-HSCT, and the correlation of SFPR and CMV infection in patients who had undergone allo-HSCT. The control group included 107 healthy donors. The SFPR group had significantly lower megakaryocyte counts, PLT, and PCT and significantly higher P-LCR, MPV, and PDW than the healthy donor and non-SFPR groups. The incidence of CMV infection was higher in SFPR patients than in non-SFPR patients. Among the patients with SFPR, P-LCR, MPV, and PDW were lower in those with CMV DNA >8000 copies/mL than in those with CMV DNA <8000 copies/mL (P < .05 for all); the CMV viral load was slightly negatively correlated with MPV (P = .0297) and P-LCR (P = .0280). We demonstrate for the first time that the level of platelet activation in SFPR patients, which was closely related to CMV infection, was higher than that in that in non-SFPR patients, and higher CMV load was associated with the inhibition of platelet activation.

Breakthrough CMV Viremia Outcomes of Letermovir Prophylaxis in Haploidentical Stem Cell Transplant with Post-Transplant Cyclophosphamide

Background Cytomegalovirus (CMV) causes significant morbidity and mortality in patients who have undergone allogeneic transplant with 45-60% mortality rates or end-organ failure related to CMV disease secondary to immunosuppression. The use of post-transplant Cyclophosphamide (PT-Cy), commonly used in haploidentical transplants (haplo-SCT), has been associated with high rates of CMV infection, reported to be 42% based on a CIBMTR analysis performed in 2021. Letermovir is FDA approved for prevention of CMV infection and disease in adult CMV-seropositive recipients [R+] undergoing allogeneic hematopoietic stem cell transplant (SCT). Despite the use of letermovir to decrease incidence of CMV, there has been limited literature on the incidence of CMV breakthrough infections in haplo-SCT patients receiving letermovir. We set out to quantify the incidence of breakthrough CMV infections in patients undergoing haplo-SCT with PT-Cy receiving letermovir prophylaxis. Endpoints The primary endpoint was to determine the incidence of breakthrough CMV reactivation (single quantifiable viral load of >200 CMV IU/mL of plasma, 2 detectable viral loads of <200 CMV IU/mL of plasma tested 3-4 days apart) both early <100 days post-transplant and late >100 days. Key secondary end points were mortality due to CMV infection, incidence of disease, end organ involvement, duration of CMV treatment, risk factors associated with CMV reactivation (based on age, sex, and seropositive status), and timing of CMV infections after haploidentical transplant. Methods This single-center, retrospective, cohort study was performed at OHSU under an IRB approved protocol. Electronic health records of patients from January 2017 to September 2021 were retrospectively reviewed to assess incidence of breakthrough CMV infection. Eligible patients were at least 18 years of age, received a haploidentical hematopoietic stem cell transplant, and received PT-Cy for graft vs host disease (GVHD) prophylaxis. Those discovered to have active CMV infections (defined as..) during conditioning who were later put on letermovir or foscarnet for treatment of their CMV reactivation were excluded. These data have been previously reported. A posthoc analysis was then performed comparing patients who received letermovir prophylaxis with a historical treatment group that underwent haplo-SCT and receive an identical treatment protocol, but did not received letermovir prophylaxis. Patients were matched by age and CMV seropositive status in a 2:1 ratio (letermovir: no letermovir), and analyzed for comparative CMV related outcomes. Results: A total of 14 eligible study subjects received letermovir prophylaxis (LP) and 7 patients did not receive letermovir prophylaxis (NLP). Overall, median age was 45 years in both groups with LP group being more male (63%) and the NLP being more female (70%) (Table 1). Thirteen of the 21 subjects received myeloablative conditioning. All subjects received PTCy, MMF until D+35 and tacrolimus goal 5-10 until D100. Letermovir was started 5 days post-transplant and stopped 100 days post-transplant. The number of patients that experienced early CMV reactivation (<100 days) was 3/14 (21.4%) and 6/7 (85.7%) in the LP and NLP treatment groups, respectively. Late CMV reactivations were rare, the LP group had 1 patient reactivate past 100 days post-transplant while there were no patients who reactivated past 100 days in the no NLP group. Mean timing of CMV viremia for the LP was significantly longer at 62 days while the NLP group was at 36.5 days. No significant risk factors were associated with age, CMV recipient seropositivity, or sex. Duration of CMV treatment was 23 days for the LP group and 21 days for the NLP group. Importantly, no patients in either cohort died of CMV (Table 2). Discussion/Conclusion: Overall, we found the LP was associated with significantly less CMV reactivations, indicating that letermovir provides effective CMV prophylaxis for patients undergoing haplo-SCT with PT-Cy. Interestingly, mean timing of CMV viremia was later for the LP group compared to the NLP group. In our cohort, we did observe 1 patient who reactivated CMV late post-transplant. This observation and the results of a study published by L.W.Liu et al. (doi: 10.1016/j.jtct.2022.05.020.) may suggest that letermovir prophylaxis past day 100 post-transplant may be indicated for haplo-SCT patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Therapeutic Drug Monitoring of Ganciclovir in Cytomegalovirus-Infected Patients With Solid Organ Transplants and Its Correlation to Efficacy and Toxicity.

Cytomegalovirus causes morbidity and mortality, especially in immunocompromised patients, and is treated with (val)ganciclovir. Therapeutic drug monitoring of ganciclovir is often performed; however, clinically established target trough levels corresponding to efficacy are lacking. In 2021, our clinic increased the target trough level for ganciclovir from 1 to 2 mg/L to 2-4 mg/L. This study aims to compare both target trough levels in efficacy, toxicity, and occurrence of resistance. A retrospective cohort study was performed in adult solid organ recipients treated for cytomegalovirus infection with (val)ganciclovir. Clinical efficacy was defined as the absence of treatment failure, defined as > 1 log 10 increase in viral load within 2 weeks of treatment initiation, therapy switch to foscarnet, and/or request for resistance analysis. A total of 46 patients were involved in the study, with 200 ganciclovir trough levels obtained. The composite endpoint was recorded in 23 (69.7%) and 10 (76.9%) patients in the 1-2 mg/L and the 2-4 mg/L group, respectively ( P = 0.18). No association was found between ganciclovir trough levels and the composite endpoint ( P = 1.0). However, a correlation was found between ganciclovir trough levels and the occurrence of lymphopenia ( P = 0.02). Our study could not establish a difference in clinical efficacy or toxicity between target trough levels of 1-2 mg/L or 2-4 mg/L because of the lack of clinical differences between the compared groups. However, a correlation was found between ganciclovir trough levels and lymphopenia, which warrants further investigation.