Reyanning Mixture on Asymptomatic or Mild SARS-CoV-2 Infection in Children and Adolescents: A Randomized Controlled Trial

Objective To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. Methods This is a prospective, open-label, randomized controlled trial. Patients aged 1–17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. Results A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5–6) vs. 7 days (IQR: 6–7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P =0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17–45.00) vs. 34.22 (IQR: 28.41–39.41), P =0.03; N gene: 34.97 (IQR: 28.50–45.00) vs. 33.51 (IQR: 27.70–38.25), P =0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72–45.00) vs. 35.81 (IQR: 29.96–45.00), P =0.003; N gene: 37.16 (IQR: 32.01–45.00) vs. 35.26 (IQR: 29.09–45.00), P =0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P =0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P <0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. Conclusion Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292)