COVID-19 treatment in children: A systematic review and meta-analysis

BACKGROUND: Exact information about the efficacy of various medications proposed by regulatory bodies in children with COVID-19 is limited due to the lack of controlled trials in the existing literature. METHODS: Different electronic databases (MEDLINE, EMBASE, Web of Science, COCHRANE CENTRAL, LitCovid, medRxiv, and bioRxiv) were searched for articles describing the management of COVID-19 cases in children with 18 shortlisted medications. Prospective/retrospective studies/case series (with at least 20 cases) reporting COVID-19 in patients aged ≤14 years were searched to collect information regarding clinical details and severity of participants, medications used, and outcome. The pooled estimate of these parameters across studies was performed using a random-effect or fixed-effect meta-analysis depending on the degree of heterogeneity. RESULTS: From a total of 5794 records, 97 studies/case series (8243 patients) fulfilled the eligibility criteria and were included in this systematic review. A total of 21% children received at least one medication specifically used for COVID-19. While antivirals were used in 15.3% of children, remedesivir was the most commonly used antiviral drug in 6.2% of included children without many reports of serious adverse effects. There was a more prevalent use of anti-inflammatory medications including corticosteroids (27.8%, P = 0.01). Total 91% of severe cases described in literature in children received some anti-inflammatory medications. Among them, corticosteroids (17%) and Intravenous immune globulin (IVIG) (17.5%) were the most predominant followed by interferon (4.2%), tocilizumab (1.5%), and anakinra (0.8%). The most predominant therapy among multisystem inflammatory syndrome in children (MIS-C) cases were IVIG (81%), followed by aspirin (67%), corticosteroids (64%), inotropes (62%), and anticoagulation (56%, mostly low molecular weight heparin, LMWH). Overall mortality was only 1.3%, but when we analyzed separately including only cases with moderate and severe disease, the mortality rate was 4.6%. CONCLUSION: Among pharmacological modalities, anti-inflammatory agents like corticosteroids and antivirals like remdesivir have the most promising evidence for severe cases of pediatric COVID-19. Intravenous immunoglobulin and other anti-inflammatory/immunomodulatory agents like anakinra, aspirin, and anticoagulants have important therapeutic role in cases with MIS-C. Most of the mild cases recover with conservative treatment only.