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

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

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)

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References

  1. World Health Organization. WHO coronavirus (COVID-19) dashboard. Accessed February 7, 2023. Available at https://covid19.who.int/.

  2. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239–1242.

    Article  CAS  PubMed  Google Scholar 

  3. Zhou JG, Lu YM, Wang LB, Yu H, Zhang T, Chen YW, et al. Pediatric patients in the new wave of SARS-CoV-2 infection in Shanghai, China. World J Pediatr 2022;18:579–581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. American Academy of Pediatrics. Children and COVID-19: state-level data report. Accessed February 7, 2023. Available at https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/.

  5. Wang L, Berger NA, Kaelber DC, Davis PB, Volkow ND, Xu R. Comparison of outcomes from COVID infection in pediatric and adult patients before and after the emergence of Omicron. medRxiv 2022. doi: https://doi.org/10.1101/2021.12.30.21268495.

  6. Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R, et al. Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement. World J Pediatr 2020;16:223–231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. World Health Organization. WHO expert meeting on evaluation of traditional Chinese medicine in the treatment of COVID-19. Accessed July 31, 2022. Available at https://www.who.int/publications/m/item/who-expert-meeting-on-evaluation-of-traditional-chinese-medicine-in-the-treatment-of-covid-19.

  8. Lyu J, Wang ZF, Xie YM, Cheng FJ, Zhang Q, Cui X. Clinical comprehensive evaluation of Reyanning Mixture in treatment of acute upper respiratory tract infection (heat-toxin attacking lung syndrome). China J Chin Mater Med (Chin) 2022;47:1476–1483.

    Google Scholar 

  9. Lyu J, Yang C, Wang LX, Xie YM, Yu XQ, Gu L, et al. Randomized double-blind parallel controlled multicenter trial of Reyanning Mixture in treatment of acute tonsillitis. China J Chin Mater Med (Chin) 2020;45:3282–3291.

    Google Scholar 

  10. Bao L, Shi YJ, Gen ZH, Sun J, Zhao RH, Du CQ, et al. Application of Reyanning Mixture in evaluating combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome. China J Chin Mater Med (Chin) 2020;45:1465–1472.

    Google Scholar 

  11. Yang MB, Dang SS, Huang S, Li YJ, Guo YL. Multi-center clinical observation of Reyanning Mixture in treatment of COVID-19. Chin J Exp Tradit Med Form (Chin) 2020;26:7–12.

    CAS  Google Scholar 

  12. Xu X, Zhou S, Chen C, Li J, Wu H, Jin G, et al. Efficacy and safety of Reyanning Mixture in patients infected with SARS-CoV-2 Omicron variant: a prospective, open-label, randomized controlled trial. Phytomedicine 2023;108:154514.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou XB, Guo J, Cao ZJ, Chu YJ, Huo GT, Qu Z, et al. Toxicological studies of Reyanning Mixture on juvenile animals. Chin Pharm Affairs (Chin) 2020;34:1040–1046.

    Google Scholar 

  14. Wang H, Chu YJ, Liu YF, Tian WZ, Liu DX, Zhang SC, et al. Multicenter clinical research to treat the acute upper respiratory tract infection in children with Reyanning Mixture. Tianjin J Tradit Chin Med (Chin) 2019;36:141–144.

    Google Scholar 

  15. Su YJ, Liu HN, Du X, Zhang XH, Zhang XJ. HPLC fingerprint of Reyanning Mixture. Modern Tradit Chin Med (Chin) 2021;41:29–33.

    Google Scholar 

  16. Xu X, Sun D, Cao M, Zhang W, Pu Y, Chen C, et al. Analysis of clinical characteristics and prognosis of 4264 patients with asymptomatic and mild novel coronavirus infections in Shanghai. Chin Critic Care Med (Chin) 2022;34:449–453.

    Google Scholar 

  17. Zhang X, Zhang W, Chen S. Shanghai’s life-saving efforts against the current Omicron wave of the COVID-19 pandemic. Lancet 2022;399:2011–2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen Z, Deng X, Fang L, Sun K, Wu Y, Che T, et al. Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study. Lancet Reg Health West Pac 2022;29:100592.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gao SJ, Guo H, Luo G. Omicron variant (B.1.1.529) of SARS-CoV-2, a global urgent public health alert! J Med Virol 2022;94:1255–1256.

    Article  CAS  PubMed  Google Scholar 

  20. World Health Organization. Enhancing response to Omicron SARS-CoV-2 variant. Accessed July 31, 2022. Available at https://www.who.int/publications/m/item/enhancing-readiness-for-omicron-(b.1.1.529)-technical-brief-and-priority-actions-for-member-states.

  21. World Health Organization. Weekly epidemiological update on COVID-19-1 February 2023. Accessed February 8, 2023. Available at https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19—1-february-2023.

  22. Li B, Zhang S, Zhang R, Chen X, Wang Y, Zhu C. Epidemiological and clinical characteristics of COVID-19 in children: a systematic review and meta-analysis. Front Pediatr 2020;8:591132.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wang L, Berger NA, Kaelber DC, Davis PB, Volkow ND, Xu R. COVID infection severity in children under 5 years old before and after Omicron emergence in the US. medRxiv 2022.01.12.22269179.

  24. Delahoy MJ, Ujamaa D, Whitaker M, O’Halloran A, Anglin O, Burns E, et al. Hospitalizations associated with COVID-19 among children and adolescents-COVID-NET, 14 States, March 1, 2020-August 14, 2021. MMWR Morb Mortal Wkly Rep 2021;70:1255–1260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gao P, Cai S, Liu Q, Du M, Liu J, Liu M. Effectiveness and safety of SARS-CoV-2 vaccines among children and adolescents: a systematic review and meta-analysis. Vaccines (Basel) 2022;10:421.

    Article  CAS  PubMed  Google Scholar 

  26. Luxi N, Giovanazzi A, Capuano A, Crisafulli S, Cutroneo PM, Fantini MP, et al. COVID-19 vaccination in pregnancy, paediatrics, immunocompromised patients, and persons with history of allergy or prior SARS-CoV-2 infection: overview of current recommendations and pre- and post-marketing evidence for vaccine efficacy and safety. Drug Saf 2021;44:1247–1269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Vangeel L, Chiu W, De Jonghe S, Maes P, Slechten B, Raymenants J, et al. Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Res 2022;198:105252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. Early remdesivir to prevent progression to severe COVID-19 in outpatients. N Engl J Med 2022;386:305–315.

    Article  CAS  PubMed  Google Scholar 

  29. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. N Engl J Med 2022;386:509–520.

    Article  PubMed  Google Scholar 

  30. Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med 2022;386:1397–1408.

    Article  CAS  PubMed  Google Scholar 

  31. FDA. Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of COVID-19. Accessed July 31, 2022. Available at https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19.

  32. Peng H, Gao P, Xu Q, Liu M, Peng J, Wang Y, et al. Coronavirus disease 2019 in children: characteristics, antimicrobial treatment, and outcomes. J Clin Virol 2020;128:104425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu XR, Zhang W, Wu XX, Huang TR, Zuo JG, Shao Z, et al. Effectiveness and safety of Baidu Jieduan Granules for COVID-19: a retrospective observational multicenter study. Chin J Integr Med 2022;28:885–893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xu X, Wu H, Jin G, Huang J, Li J, Zhou J, et al. Efficacy of Lianhua Qingwen for children with SARS-CoV-2 Omicron infection: a propensity score-matched retrospective cohort study. Phytomedicine 2023;111:154665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the Jiangxi Medical Team for coming to support Shanghai and making important contributions to the battle against the epidemic in Shanghai. We thank the medical staff of Jiujiang Hospital of Traditional Chinese Medicine and Longhua Hospital for the coordination and data management of this study.

Author information

Authors and Affiliations

  1. Department of Emergency, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

    Xiang-ru Xu, Wei Peng, Wen Zhang, Ding Sun & Bang-jiang Fang

  2. Acupuncture and Massage College, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Shuang Zhou

  3. Department of Health Management, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Guo-qiang Jin

  4. Jiangxi Provincial Traditional Chinese Medicine Nephropathy Clinical Research Center, Jiujiang Hospital of Traditional Chinese Medicine, Jiujiang, Jiangxi Province, 332099, China

    Hong-ze Wu & Jin-hua Li

  5. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Jing Zhou

  6. Institute of Critical Care, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

    Bang-jiang Fang

Authors
  1. Xiang-ru Xu
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  2. Shuang Zhou
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  4. Hong-ze Wu
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  5. Jin-hua Li
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  6. Jing Zhou
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  7. Wei Peng
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  8. Wen Zhang
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  10. Bang-jiang Fang
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Contributions

Fang BJ was responsible for funding acquisition and supervising the study. Jin GQ, Wu HZ, Li JH, and Zhou J were responsible for investigation. Zhang W, Peng W, and Sun D were responsible for methodology. Xu XR was responsible for writing original draft and software. Zhou S was responsible for review writing and editing. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Bang-jiang Fang.

Ethics declarations

The authors have no financial conflicts of interest to declare.

Additional information

Supported by the National Traditional Chinese Medicine Multidisciplinary Innovation Team Project (No. ZYYCXTD-D-202203), National Traditional Chinese Medicine Emergency Medical Rescue Base Construction (No. ZY(2021-2023)-0101-01), World Federation of Chinese Medicine Societies Project (No. SZL-2022YI010), and Emergency Tackle Project on COVID-19 Omicron Infection of Shanghai University of Traditional Chinese Medicine (No. 2022YJ-03)

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Xu, Xr., Zhou, S., Jin, Gq. et al. Reyanning Mixture on Asymptomatic or Mild SARS-CoV-2 Infection in Children and Adolescents: A Randomized Controlled Trial. Chin. J. Integr. Med. 29, 867–874 (2023). https://doi.org/10.1007/s11655-023-3609-0

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  • DOI: https://doi.org/10.1007/s11655-023-3609-0

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