Whether the timing of patient randomization interferes with the assessment of the efficacy of ruxolitinib for severe COVID-19

To the Editor:

We read with great interest the article titled ‘‘Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial’’ by Cao et al.¹ The study, which finally included 41 patients, evaluated the efficacy and safety of ruxolitinib for severe COVID-19 cases. They found that ruxolitinib recipients had a significant chest computed tomography (CT) improvement, a faster recovery from lymphopenia, and favorable side-effect profile. However, we think it is appropriate to comment on the methods used in this study.

First, the duration from illness onset to randomization, 22 days for the control group and 20 days for the ruxolitinib group, was not appropriate because according to literature reports,2, 3, 4 the course (from illness onset to discharge) of severe patients was about 27 to 30 days. Therefore, the patients may have passed the dangerous period at the 20th day and be in the end stage of the disease, which corresponds to the improvement period.

Second, in terms of the extent of CT abnormalities, COVID-19 showed a marked increase from the subclinical period through the first and second weeks after illness onset, then decreased gradually in the third week.5, 6, 7 Therefore, it is difficult to say whether the absorption of patients after the 20th day was the process of disease outcome or the effect of ruxolitinib.

Finally, using the data of CT improvement at day 14 in Table III, we found that the P value between the control group and the treatment group was not .0495 but .079.

Nevertheless, these small issues in no way detract from the outstanding work of Cao et al, which sheds light on the treatment of COVID-19.