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

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.

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.

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%.

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.