Potential Effectiveness and Safety of Antiviral Agents in Children with Coronavirus Disease 2019: A Rapid Review and Meta-Analysis

Shi, Qianling; Zhou, Qi; Wang, Xia; Liao, Jing; Yu, Yang; Wang, Zijun; Lu, Shuya; Ma, Yanfang; Xun, Yangqin; Luo, Xufei; Li, Weiguo; Fukuoka, Toshio; Ahn, Hyeong Sik; Lee, Myeong Soo; Luo, Zhengxiu; Liu, Enmei; Che, Yaolong; Li, Qubei; Yang, Kehu

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 from their inception to March, 31 2020 were searched for randomized controlled trials, 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 of indirect evidence with 6008 patients were included. 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) and probability of negative PCR test (RR=0.98, 95 CI% 0.82 to 1.18). Arbidol had no benefit on probability of negative PCR test (RR=1.27, 95% CI 0.93 to 1.73). Hydroxychloroquine was not associated with increasing the probability of negative PCR result (RR=0.93, 95% CI 0.73 to 1.18). 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; children; COVID-19; meta-analysis; rapid review.