The COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, has led to significant morbidity and mortality worldwide. The Omicron variant, first detected in South Africa in November 2021, has since spread rapidly and caused over 10 million confirmed cases and over 18,000 deaths in Taiwan [1,2].

The development of oral antiviral drugs has been a strategy to reduce the morbidity and mortality associated with COVID-19. Nirmatrelvir/ritonavir and molnupiravir received emergency use authorization from the US Food and Drug Administration. Previous studies have shown that the rate of hospitalisation or death decreased by 31% with molnupiravir and 89% with nirmatrelvir/ritonavir compared with placebo [3,4].

Relative to mild or moderate cases, the mortality rate is substantially elevated in severe or critical COVID-19 pneumonia, ranging from 16% to 78% [5], [6], [7]. However, for COVID-19 patients with moderate to severe disease requiring hospitalisation, it remains uncertain whether oral antiviral therapy administered during the early mild disease stage can decrease disease progression to critical illness or mortality. Therefore, this study aimed to investigate the effect of oral antiviral administration before hospitalisation in patients with moderate-to-severe COVID-19 pneumonia, to reduce the risk of progression to critical illness or mortality in patients with COVID-19.