Baseline characteristics
A total of 200 convalescent COVID-19 patients from three centers were enrolled and assessed for eligibility, with 100 patients in each group after randomization. Three patients dropped out of the study because of poor compliance, violation of the treatment protocol, or adverse events; four patients did not meet the inclusion criteria, one patient repeatedly recorded. Totally, 192 patients fully completed the study. (Figure 1)
The demographic and baseline characteristics were shown in Table 1. There was no significant difference in gender, age, smoking, drinking, drug allergy history, systolic blood pressure, diastolic blood pressure, resting heart rate, breathing, CT imaging, hospitalization length, discharge length, comorbidities and concomitant medication between groups (P > 0.05). The body mass index value was significantly lower in Ludangshen group than control group (P = 0.021).
Comparison of symptom scores
At week 1, fatigue score was significantly lower in Ludangshen group compared to that in placebo group (FAS: P < 0.001; PPS: P < 0.001). Ludangshen group had significantly lower symptom score in anorexia, distension, loose stools and shortness of breath compared to placebo group for FAS analysis, but the PPS analysis showed not significantly difference between groups (FAS: P < 0.001, P = 0.024, P = 0.001, P = 0.016; PPS: P = 0.535, P = 0.619, P = 0.749, P = 0.996) (Table 2).
At week 2, patients in Ludangshen group had significantly lower score of fatigue, anorexia, loose stools, and shortness of breath (FAS: P < 0.001, P < 0.001, P = 0.001, P < 0.001; PPS: P < 0.001, P < 0.001, P = 0.001, P < 0.001). There was no significant difference in distension score between the two groups (FAS: P = 0.987; PPS: P = 0.341) (Table 2).
Comparison of symptom improvement rate
At week 1, the improvement rates of fatigue and anorexia were significantly higher in Ludangshen group than placebo group (FAS: P = 0.002, P < 0.001; PPS: P = 0.003, P < 0.001). Patients in Ludangshen group also had obviously higher improvement rate in distension and loose stools by FAS analysis, but the differences were not significant by PPS analysis (FAS: P = 0.036, P = 0.039; PPS: P = 0.059, P = 0.062). For shortness of breath, there was no significant difference between groups (FAS: P = 0.23; PPS: P = 0.312). (Table 3)
At week 2, the improvement rate of fatigue, anorexia, distension, loose stools, and shortness of breath were all significantly higher in Ludangshen group compared to placebo group (FAS: P < 0.001, P = 0.013, P = 0.007, P < 0.001, P < 0.001; PPS: P < 0.001, P < 0.001, P = 0.01, P = 0.005, P = 0.001). (Table 3)
Comparison of symptom disappearance rate
At week 1, the symptom disappearance rate of fatigue and anorexia were significantly higher in Ludangshen group than placebo group (FAS: P = 0.027, P = 0.036; PPS: P = 0.026, P < 0.001). For distension, loose stools, and shortness of breath, there were no statistically significant difference in symptom disappearance rate between groups (FAS: P = 0.194, P = 0.07, P = 1; PPS: P = 0.197, P = 0.058, P = 1). (Table 4)
At week 2, the symptom disappearance rate of fatigue, anorexia, distension and loose stools were significantly higher in Ludangshen group than placebo group (FAS: P < 0.001, P < 0.001, P = 0.005, P = 0.005; PPS: P < 0.001, P < 0.001, P = 0.002, P = 0.002). There was no statistically significant difference in symptom disappearance rate of shortness of breath between groups (FAS: P = 0.11; PPS: P = 0.11). (Table 4)
Safety evaluation
The adverse events were recorded during the study. There were two cases of adverse events. One case in Ludangshen group had nose bleeding, and one case in placebo group had headache. The rate of adverse events was 1% in both groups (P > 0.05). There were no significant differences in systolic blood pressure, diastolic blood pressure and resting heart rate at the end of treatment between Ludangshen and placebo group (P > 0.05).