High-dose budesonide for early COVID-19

The importance of effective community-based treatments for COVID-19 cannot be overstated. We applaud Ly-Mee Yu and colleagues¹ for addressing this issue in the PRINCIPLE trial and would like to share some comments.

The study included participants onset of COVID-19 within 14 days; however, those closer to 14 days since illness onset might be approaching spontaneous resolution, which could confound effectiveness and expose patients to unnecessary inhaled corticosteroids. We are concerned that the subjective self-reporting of obesity might be biased and wonder if any criteria were placed for participants to classify themselves as obese. Likewise, symptom severity was self-reported from no problem to major problem.¹ Was this subjective scale controlled for, particularly in quantifiable variables like fever.

It is important to understand the illness severity of the study population, such as how many participants were symptomatic versus asymptomatic at enrolment, how many were compliant with treatment versus non-adherent, and if there were any outcome differences among them. We are curious if time from enrolment to treatment initiation differed among participants. The Article's Table 1 includes 833 participants from the inhaled budesonide group and 1126 participants from the usual care group, respectively, which does not coincide with the 787 and 1069 included for primary analysis.¹

Finally, the study faced limitations such as the predominantly white population (92%), which does not represent the high-risk community, the small number of participants with chronic lung conditions due to exclusion of those taking corticosteroids, and the self-reported nature of symptoms, which could be inaccurately assessed and biased by multiple factors.

We declare no competing interests.