Montoya, José G.

Cytomegalovirus (CMV) establishes lifelong latency following primary infection and can reactivate to cause severe illness in immunocompromised hosts. CMV DNAemia in non-HIV-infected, non-solid organ/bone marrow transplant (NHNT) hosts is poorly characterized, with limited clinical insights. We aim to describe the clinical presentation, prognostic indicators, and outcomes of CMV DNAemia among NHNT patients. We used the TriNetX international patient database to identify adult patients diagnosed with CMV DNAemia from 2016 until March 2023. We evaluated hospitalization, intensive care unit (ICU) level care, and all-cause mortality at 30 days and 1 year. We also completed a post-propensity score analysis comparing clinical characteristics of survivors versus non-survivors at 90 days. We identified 1123 NHNT patients with CMV DNAemia, most of whom had neoplasms (63%). Venous thromboembolism occurred in 31% of the population. The 30-day hospitalization and all-cause mortality rates were 35% and 14%, respectively. After propensity score matching and Bonferroni correction, weakness, purpura, acute respiratory failure, malnutrition, encephalopathy, and hypotension were associated with increased 90-day all-cause mortality. NHNT patients with CMV DNAemia carry a substantial morbidity and all-cause mortality. Further studies are warranted to clarify whether CMV DNAemia is a causative factor or an incidental finding in this population.

Abstract Background Cytomegalovirus (CMV) infects millions in the US and is a source of comorbidity among immunocompromised patients. Despite its prevalence, there is limited data on clinical characteristics or outcomes among HIV-negative, non-transplant (NHNT) patients in population-based cohorts. We aim to evaluate a multicenter US-based network to obtain clinical characteristics and outcomes of NHNT patients with CMV disease and explore potential prognostic clinical characteristics implicated in increased morbidity and mortality. Methods This is a US-based multicenter, population-based, retrospective cohort study. We queried TrinetX, a global research network, to identify patients with a CMV disease by ICD-10-CM codes and serum and PCR > 5000 IU/mL. We captured comorbidities diagnosed within 90 days of CMV infection diagnosis, symptoms noted within 30 days, and outcomes of interest at 30 days and 1 year. Primary outcome was all-cause mortality. Secondary outcomes were hospitalization and CMV disease-related complications. We performed a propensity score-matched analysis comparing clinical characteristics among patients who survived versus non-survivors at 90 days. Results We found 1123 patients with evidence of CMV disease. The mean patient age was 53 years, 48% men and 50% white. Aplastic anemia and neoplasms were the most common comorbidities (Table 1). Thromboembolism was a common complication (15%). Half of the patients had dyspnea, fever, abdominal pain, and nausea. CMV disease was associated with 14%, 22%, and 26% mortality at 30 days, 90 days, and one year, respectively. 35% of patients required hospitalization within 30 days. After propensity score matching, we had 278 patients in each cohort. Dyspnea and weakness were linked to increased 90-day mortality (Figure 1). Purpura, encephalopathy, and sepsis were more common in patients who died. High CMV serum viral load and ferritin were associated with increased mortality. Conclusion NHNT patients with CMV disease often have underlying comorbidity, commonly aplastic anemia, and neoplasms. CMV disease was associated with thrombosis and a high risk of hospitalization and mortality. Vascular disease, sepsis, high viral load, and cell lysis markers were prognostic factors for mortality in this cohort. Disclosures Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

SUMMARY Chromosomally integrated human herpesvirus 6 (ciHHV‐6) is a condition in which the complete HHV‐6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV‐6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV‐6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV‐6 due to cell lysis and release of cellular DNA. High HHV‐6 DNA loads associated with ciHHV‐6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV‐6 may be at increased risk for bacterial infection and graft rejection. ciHHV‐6 can be induced to a state of active viral replication in vitro . It is not known whether ciHHV‐6 individuals are put at clinical risk by the use of drugs that have been associated with HHV‐6 reactivation in vivo or in vitro . Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV‐6. Little is known about whether individuals with ciHHV‐6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV‐6 in disease. Copyright © 2011 John Wiley & Sons, Ltd.