Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis

Qianling Shi; Qi Zhou; Xia Wang; Jing Liao; Yang Yu; Zijun Wang; Shuya Lu; Yanfang Ma; Yangqin Xun; Xufei Luo; Weiguo Li; Toshio Fukuoka; Hyeong Sik Ahn; Myeong Soo Lee; Zhengxiu Luo; Enmei Liu; Yaolong Chen; Qubei Li; Kehu Yang; Quanlin Guan; COVID-19 Evidence and Recommendations Working Group

doi:10.21037/atm-20-3301

Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis

Ann Transl Med. 2020 May;8(10):624. doi: 10.21037/atm-20-3301.

Authors

Qianling Shi¹, Qi Zhou^{1

2}, Xia Wang^{3

4

5}, Jing Liao^{3

4

5}, Yang Yu⁶, Zijun Wang², Shuya Lu^{7

8}, Yanfang Ma², Yangqin Xun², Xufei Luo^{2

9}, Weiguo Li^{3

4

5}, Toshio Fukuoka^{10

11}, Hyeong Sik Ahn^{12

13}, Myeong Soo Lee^{14

15}, Zhengxiu Luo^{3

4

5}, Enmei Liu^{3

4

5}, Yaolong Chen^{2

16

17

18}, Qubei Li^{3

4

5}, Kehu Yang^{1

2

18}, Quanlin Guan^{1

19}; COVID-19 Evidence and Recommendations Working Group

Affiliations

¹ The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China.
² Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
³ Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁴ National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁵ Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
⁶ The Second School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China.
⁷ Department of Pediatric, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China.
⁸ Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China.
⁹ School of Public Health, Lanzhou University, Lanzhou 730000, China.
¹⁰ Emergency and Critical Care Center, Department of General Medicine, Department of Research and Medical Education at Kurashiki Central Hospital, Kurashiki, Japan.
¹¹ Advisory Committee in Cochrane Japan, Tokyo, Japan.
¹² Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea.
¹³ Korea Cochrane Centre, Seoul, Korea.
¹⁴ Korea Institute of Oriental Medicine, Daejeon, Korea.
¹⁵ University of Science and Technology, Daejeon, Korea.
¹⁶ Lanzhou University, An Affiliate of the Cochrane China Network, Lanzhou 730000, China.
¹⁷ Chinese GRADE Center, Lanzhou 730000, China.
¹⁸ Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou 730000, China.
¹⁹ Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China.

Abstract

Background: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children.

Methods: Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19.

Results: A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions.

Conclusions: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.

Keywords: Antiviral agents; COVID-19; children; meta-analysis; rapid review.