Influenza and other respiratory viruses are underdiagnosed in critically ill patients.

To the Editor: In a recent issue of Critical Care Medicine, we read with great interest the article by Ortiz et al (1) on the estimated burden of influenza virus infections in the critically ill and the comparison with hospitalization discharge databases. The authors estimated that influenza infections accounted for 1.3% of all ICU admissions, which increased to 3.4% of all ICU admissions during the influenza season. However, the influenza diagnoses as deduced from International Classification of Diseases, 9th Edition codes were only reported in 2,612 cases out of a predicted 26,760 cases, which strongly suggests that influenza is underdiagnosed and/or underreported in the critically ill. Given that detection of influenza virus has implications for treatment decisions, infection control measures, and public health (2, 3), this may be considered a problem. In a recent multicenter prospective observational feasibility study, we assessed the prevalence of viral respiratory tract infections in ICU patients as well as the percentage of infections missed in daily practice. During March and April 2013 in three ICUs in the Netherlands, consecutive acutely admitted and intubated critically ill patients were included. A nasopharyngeal swab and a tracheobronchial aspirate were obtained at inclusion. Samples were tested via multiplex reverse transcriptase-polymerase chain reaction for a panel of viruses, including influenza. Results of viral diagnostics performed in routine care were collected and compared with the test results found in this study (4). Of all 128 acutely admitted ICU patients, 35 (27%) tested positive for at least one virus. Of these, seven patients (5.5%) had an infection with influenza. Of note, of the patients with a viral respiratory tract infection, 40% tested negative on the nasopharyngeal swab but positive on the tracheobronchial aspirate. Thereby, diagnostic accuracy of nasopharyngeal swabs may be limited, which may account at least in part for underdiagnosing of viral infections if only the upper airways are sampled. Also, in only 10 of 35 virus-positive patients, the attending physician had requested virus diagnostics in routine care, thereby missing about 70% of viral respiratory tract infections. A possible explanation for the lack of ordering tests, also alluded to by the authors (1), may be that by focusing on clinical diagnosis as community-acquired pneumonia and hospital-acquired pneumonia, the virus-induced nonpneumonia diseases will be missed, such as exacerbations of chronic underlying conditions. Although we did not collect clinical data to strengthen this hypothesis, which is a major limitation of this study, our prospective data underline on the conclusion of Ortiz et al (1) that viral respiratory tract infections are underdiagnosed in ICU patients. The accuracy and implications of these results need to be further investigated and will be addressed in a larger prospective observation study (5). There remains a paucity of data regarding prevalence, burden, and clinical implications of viral respiratory tract infections in critically ill patients as well as clear diagnostic guidelines on which patients should be tested and what methods to use. The authors’ institutions received grant support from Crucell Holland BV (Leiden, The Netherlands. The AMC Medical Research BV received financial support for covering personnel, logistic, and laboratory costs associated with this study. The sponsor had no role in study design; collection, management, analysis, and interpretation of the data; preparation, review, and decision to submit scientific articles). Dr. de Jong’s institution consulted for Crucell Holland BV (Scientific Advisory Board National Institutes of Health project), AIMM Therapeutics (Scientific Advisory Board), GSK (Independent Data Monitoring Committee [IDMC] phase 3 trial flu antiviral), and Vertex (IDMC phase 2 trial flu antiviral). Dr. Juffermans’ institution received grant support from Sanquin, ZOnMW, and FP7 (unrelated to this study).