Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review

Abstract

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known:• The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New:• Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C.• We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.

Efficacy and safety of vitamin D supplementation in hospitalized COVID-19 pediatric patients: A randomized controlled trial

“…Although multiple treatments have been evaluated since the beginning of the COVID-19 pandemic: chloroquine or hydroxychloroquine, azithromycin, ivermectin, lopinavir/ritonavir, convalescent plasma, intravenous immunoglobulin, and interleukin (IL)-6 inhibitors, none of them have proven efficacy and safety in the pediatric population. However, despite the evidence in pediatric patients being insignificant and of low quality ( 3 , 4 ), some guidelines recommend the use of remdesivir in critically ill patients ( 2 , 5 ).…”

Guidelines for the prevention and management of children and adolescents with COVID-19

“…Our systematic review identified three single-arm cohort studies with 112 children and adolescents with COVID-19, with data collected between January 2020 and August 2021 [ 30 ]. In one of these studies, all patients had severe COVID-19 [ 37 ]; in another study, 75% of the patients were admitted to the pediatric intensive care unit (PICU) [ 38 ]; and in the third study, 22% of the patients received mechanical ventilation [ 39 ].…”

“…Our systematic review, which included one prospective cohort study and one case series with a total of 69 children and adolescents with COVID-19, with data collected between January 2020 and August 2021, did not find statistically significant impact of glucocorticoid therapy on the critical outcomes mortality (OR 2.79, 95% CI: 0.13 to 60.87), mechanical ventilation (OR 2.83, 95% CI: 0.78 to 10.30), or duration of PICU admission (weighted mean differences [WMD] 2.0, 95% CI: − 0.95 to 4.95) when compared with no glucocorticoid therapy [ 30 ].…”

“…Our systematic review identified four cohort studies of children and adolescents with MIS-C with data collected between January 2020 and August 2021[ 30 ]. The review showed that 64 patients receiving IVIG (2 g/kg) as the only first-line therapy had a treatment success rate of 62% (treatment failure was defined as the persistence of fever 2 days after the introduction of first-line therapy or recrudescence of fever within 7 days after the beginning of the first-line therapy treatment).…”

“…One of the cohort studies included in our systematic review [ 30 ] found that 32 MIS-C patients with a severe initial clinical presentation at the time of diagnosis (acute left ventricular dysfunction, admission to PICU care, or need of hemodynamic support) who received a combination of IVIG and methylprednisolone (0.8–1 mg/kg/12 h for 5 days; or 15–30 mg/kg/day for 3 days) as first-line therapy had lower odds of treatment failure (OR 0.25, 95% CI: 0.09 to 0.70), need of second-line treatment (OR 0.19, 95% CI: 0.06 to 0.61) and hemodynamic support (OR 0.21, 95% CI: 0.06 to 0.76), and occurrence of secondary acute left ventricular dysfunction (OR 0.20, 95% CI: 0.06 to 0.66) compared with 64 MIS-C patients who received IVIG alone (2 g/kg, single dose) as first-line therapy [ 61 ]. One study ( n = 40) showed that 22 MIS-C patients who received a combination of IVIG and methylprednisolone (0.8 mg/kg/d for 5 days) had a shorter time to recovery of left ventricle ejection fraction (2.9 vs. 5.4 days, p = 0.002) than the remaining 18 patients who received IVIG alone (2 g/kg, single dose) as first-line therapy [ 62 ].…”