Tang X, Du R, Wang R, et al. - Considering the significance to differentiate Coronavirus Disease 2019 (COVID-19) from other respiratory infectious diseases, such as influenza viruses, for clinicians and epidemiologists, researchers here explored the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with acute respiratory distress syndrome (ARDS). In this retrospective case-control study, two independent cohorts of ARDS patients infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Observations revealed many differences in clinical presentations between COVID-19 and H1N1-induced ARDS patients. The median age was higher for COVID-19 patients vs H1N1 patients, and males were in higher proportion among COVID-19 patients. Non-productive coughs, fatigue, and gastrointestinal symptoms were evident in higher proportion of COVID-19 patients vs H1N1 patients. COVID-19 patients had significantly higher partial pressure of oxygen/fractional inspired oxygen of 198.2 mmHg vs 107.0 mmHg in H1N1 patients. COVID-19 patients more commonly exhibited Ground-glass opacities than H1N1 patients. Relative to H1N1 patients, COVID-19 patients were administered a greater variety of antiviral therapies. They observed lower severity of illness scores at presentation and lower sequential organ failure assessment-score adjusted mortality among patients with COVID-19 induced ARDS vs H1N1.