Clinical Features and Outcomes of Human Herpesvirus-6 DNAemia in Critically Ill Patients: A Retrospective Multicenter Analysis

BACKGROUND: Human herpesvirus-6 (HHV-6) DNAemia is not rare in intensive care unit (ICU) patients. However, evidence for a causal association of HHV-6 DNAemia with organ disease and with mortality is limited in this setting. In ICU patients with HHV-6 DNAemia, we sought to (1) assess the prevalence of HHV-6 disease, (2) identify risk factors for HHV-6 disease, and (3) investigate its association with mortality. METHODS: This was a retrospective multicenter case-matched study in 3 ICUs from January 2011 to January 2022 of patients with HHV-6 viral load in whole blood (genome equivalent copies/106 cells) detected during the ICU stay. RESULTS: A total of 168 patients were included. Seventeen (10%) were classified as having HHV-6 disease (ie, HHV-6 DNAemia with attributable end-organ disease) and 151 (90%) as HHV-6 reactivation (ie, HHV-6 DNAemia without any attributable end-organ disease). Immunosuppression was significantly more frequent in patients with HHV-6 (100% vs 48%; P < .001). Eleven (65%) patients with HHV-6 disease received hematopoietic stem cell transplantation (HSCT). End-organ diseases were encephalitis (n = 10) and pneumonia (n = 7). ICU mortality was 32% (n = 53). In multivariate analysis, HHV-6 disease remained independently associated with ICU (odds ratio [OR]: 4.90) and 90-day (hazard ratio: 2.25) mortality. Mortality remained significantly higher in the HHV-6 disease group (OR: 4.30) compared with matched ICU patients without HHV-6 DNAemia. CONCLUSIONS: Our analysis suggests that HHV-6 disease develops in 10% of patients with HHV-6 detection in the ICU, mostly in the setting of allogeneic HSCT, and is independently associated with ICU and 90-day mortality.