Influenza and common cold viruses in critically ill adults

There is an increasing appreciation of common cold respiratory viruses as causal agents of critical illness in adults. However, challenges remain regarding disease burden estimates, interpretation of molecular test results, deployment of clinical diagnostics, and clinical management of viral respiratory tract infections (RTIs).
This thesis aims to advance insights into the role of influenza and common cold viruses in critically ill adults, and guide diagnostics, treatment and infection control measures. Firstly, we found that viral RTIs are frequently detected in critically ill adults admitted to the intensive care unit (ICU). Secondly, we addressed the clinical interpretation of detecting a respiratory virus in critically ill patients, as detection does not automatically imply a causative role in the presenting illness. The presented prospective cohort with case-control design allows for estimates of these coincidental infections. The findings point to a substantial burden of common cold virus-associated severe disease in adults, although confounding remains challenging. Next, the practice of clinical diagnostics was addressed. Our findings indicate that many viral RTIs, including influenza, are missed in the adult ICU setting, and including a sample from the lower respiratory tract greatly increases diagnostic yield. Lastly, shedding dynamics were studied. In the majority of patients viral RNA remained detectable throughout invasive mechanical ventilation. Also, viral RNA shedding was significantly longer in samples from the lower respiratory tract, and associated with a fatal outcome. Potential implications for infection control measures and decisions on the duration of influenza treatment are discussed.