Immunostimulants for preventing respiratory tract infection in children: A systematic review and meta-analysis

Childhood acute respiratory tract infections (ARTIs) are a significant cause of morbidity and mortality, so, immunostimulants have been used as a preventative measure. Despite this, there is no updated evidence regarding the safety and efficacy of immunostimulant drugs for this purpose. This study aimed to determine the effectiveness and safety of immunostimulants in preventing ARTIs in children based on the most recent scientific evidence. Data sources such as PubMed, Cochrane Central Register of Controlled Trials, Embase, Google Scholar, and Scopus were searched from 1965 to 10 January 2022 to identify randomized controlled trials (RCTs) comparing immunostimulants administered by any method, with placebo to prevent ARTIs on children under 18 years of age without immunodeficiencies, anatomical, genetic, or allergic conditions. In order to analyze data from the studies, we used Review Manager 5.4 (The Cochrane Collaboration, 2020), assessed the certainty of the evidence with Grading of Recommendations, Assessment, Development and Evaluations (GRADE), and assessed the quality and risk of bias of the studies using the RoB tool 1.0. Further, outcomes were combined and analyzed using meta-analysis, subgroup analysis, and sensitivity analysis. Throughout the review, we included 72 placebo-controlled clinical trials involving 12,229 children. The meta-analyses, however, included only 38 studies (52.8%) with 4643 children (38% of the total) with data on mean number of ARTIs. These studies demonstrated a reduction in the ARTIs (MD –1.12 [95%CI –1.39 to −0.85]) and ratio of means of ARTIs (0.61 [95%CI 0.54–0.69]), corresponding to a percentage reduction of 39% (95%CI, 46%–31%) with moderate-quality data. Nevertheless, since there was considerable to substantial heterogeneity and bias was unclear in all domains in 32 out of 72 trials, the quality of the evidence for efficacy was deemed low. Only 14 trials reported adverse events. The review indicates that immunostimulants reduce the incidence of ARTIs by 40% on average in susceptible children, despite low-quality evidence, heterogeneity, and the possibility of publication bias. However, further studies are needed to establish immunostimulants' safety and efficacy profiles. This review was conducted without the support of any funding and has no registered number.