Multi-omics profiling in severe pneumonia: the importance of robust study design

Early in the COVID-19 pandemic, many clinical and translational reports described the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen from a standpoint of exceptionalism [1, 2]. These reports sought to describe the clinical presentation and pathobiology of COVID-19 as a unique entity without comparison to other community-acquired pathogens or conditions that cause severe pneumonia, respiratory failure and the acute respiratory distress syndrome. For example, early studies suggested the presence of a “cytokine storm” that was peculiar to severe and critical COVID-19 [3–7]. Nevertheless, subsequent analyses found that cytokine levels are similar in patients with severe SARS-CoV-2 pneumonia and those with pneumonia due to other causes and respiratory failure, although the distinctly long duration of illness in patients with COVID-19 results in greater cytokine exposure over time [8, 9]. The importance of comparing COVID-19 with other forms of pneumonia is not simply academic. Some therapies proven to be effective in severe SARS-CoV-2 pneumonia, such as corticosteroids [10], may be ineffective or harmful in patients with other aetiologies of pneumonia [11].