Dear Editor,

Viral respiratory infections are a leading cause of illness and hospitalization in young children worldwide. Adenoviral respiratory tract infections occur primarily in infants and young children and can manifest as bronchiolitis, exacerbations of wheezing and asthma, croup, pneumonia and pneumonitis in transplant recipients [1]. We investigated the impact of adenovirus on morbidity and mortality outcomes in children with severe viral respiratory infection.

Following approval by our institutional review board, we performed a retrospective cohort study identifying all patients with laboratory-confirmed adenoviral respiratory infection admitted to the pediatric or cardiac intensive care unit (ICU) at our institution between January 2010 and May 2012. Infection was defined as the identification of adenovirus from a nasopharyngeal or endotracheal specimen by polymerase chain reaction testing.

There were 302 patients with laboratory-confirmed adenoviral respiratory infection admitted to our institution during the period of study, of whom 100 (33 %) were admitted to one of the ICUs. The median age of the patients was 20 months (interquartile range, IQR, 12–44 months). The median hospital length of stay was 8 days (IQR 3–20 days) and the median ICU length of stay was 4 days (IQR 1–13 days). Seven patients (7 %) did not survive to discharge. Respiratory failure was the primary cause of death in all seven patients. We compared patient characteristics and clinical factors between survivors and nonsurvivors (Table 1).

Table 1 Characteristics of patients admitted to the ICU with adenoviral respiratory infection stratified by survival

We constructed a multivariate logistic regression model incorporating significant predisposing factors and a priori confounders. Adjusting for age, hospital acquisition of infection and Paediatric Index of Mortality 2 score, the logistic regression analysis demonstrated that an immunocompromised state independently increased the odds of mortality. Immunocompromised patients had a 136 times greater odds (p = 0.001) of mortality compared with immunocompetent patients.

The seven nonsurvivors included one previously healthy child, one patient with neurodegenerative disease, one patient who had undergone liver and small-bowel transplantation, one patient with acute myeloid leukemia who presented with neutropenia, and three patients who had undergone hematopoietic stem cell transplantation. Four patients, all of whom were immunocompromised, received cidofovir therapy. None of these patients survived.

It has been recognized for several years that adenovirus carries with it high morbidity and mortality among immunocompromised patients [2]. This is the first study that we are aware of that has assessed morbidity and mortality outcomes of respiratory illness caused by adenovirus in a pediatric ICU setting. Similar to previous studies of respiratory syncytial virus and influenza, we found that immunocompromised children with respiratory illness had increased mortality [3, 4].

There is no specific antiviral therapy approved for use in adenovirus. Recently, cidofovir has been increasingly used in pediatric hematopoietic stem cell transplant patients with adenoviral infection despite the lack of randomized controlled trials [5]. Further research is needed to investigate the efficacy of cidofovir for the treatment of adenoviral respiratory infection in immunocompromised patients.

In conclusion, the burden of illness on the ICU from severe adenoviral respiratory infection may be substantial. An immunocompromised state independently increases mortality.