This thesis bundles a collection of studies of (1) airway care interventions in ventilated critically ill patients in general, and (2) prone positioning in intensive care unit (ICU) patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID–19). Invasively ventilated critically ill patients frequently undergo airway care interventions, like ‘endotracheal suctioning’, ‘manual hyperinflation’, ‘nebulizations’ and ‘mechanical insufflation-exsufflation’. All airway care interventions have in common that they are meant to prevent mucus accumulation in the airways, thereby possibly preventing complications. Evidence for benefit from airway care interventions in invasively ventilated critically ill patients, however, is surprisingly absent. Indications for their use vary and clinical mucus classifications do not seem to correlate with rheological properties. There is a wide variety in how these interventions are applied in daily ICU practice. Prone positioning can improve oxygenation. Before the COVID–19 pandemic, prone positioning was recommended to be used only in invasively ventilated patients with moderate to severe ARDS. During the pandemic, prone positioning started to become one of the most frequently used rescue therapies for hypoxemia patients with COVID–19 ARDS. Moreover, prone positioning was increasingly used in patients that are not intubated.