Clinical features and outcomes of Human Herpesvirus-6 DNAemia in critically ill patients: a retrospective multicenter analysis

Abstract

Introduction: 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: Retrospective multicenter case-matched study in three ICUs from January 2011 to January 2022 of patients with HHV-6 viral load in the whole blood (genome equivalent copies/106 cells) detected during the ICU stay.

Results: One hundred and sixty-eight patients were included. Seventeen (10%) were classified as HHV-6 disease (i.e., HHV-6 DNAemia with attributable end-organ disease) and 151 (90%) as HHV-6 reactivation (i.e., HHV-6 DNAemia without any attributable end-organ disease). Immunodepression was significantly more frequent in HHV-6 disease patients (100% vs. 48%, p < 0.001). Eleven (65%) HHV-6 disease patients received hematopoietic stem cell transplantation (HSCT). End-organ diseases were encephalitis (n = 10) and pneumonia (n = 7). The ICU mortality was 32% (n = 53). In multivariate analysis, HHV-6 disease remained independently associated with ICU (OR 4.90) and 90-day (HR 2.25) mortality. Mortality remained significantly higher in the HHV-6 disease group (OR 4.30) when compared to matched ICU patients without HHV-6 DNAemia.

Conclusion: 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.

Keywords: Human Herpesvirus-6; encephalitis; hematopoietic stem cell transplant; idiopathic pneumonia syndrome; intensive care unit.