1. This meta-analysis demonstrated that studies investigating ivermectin treatment for COVID-19 in areas of low strongyloidiasis prevalence revealed no decrease in mortality risk; conversely, a decrease in mortality was found with ivermectin treatment in studies conducted in regions of high strongyloidiasis prevalence.

2. Meta-regression analysis resulted in a 39% decrease in relative risk of mortality from COVID-19 for every 5% increase in strongyloidiasis prevalence.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Ivermectin is a well-known anti-parasitic drug. There has been growing attention given to ivermectin after a recent review demonstrated its effectiveness at reducing the risk of mortality in COVID-19 infected patients. However, a critical, uncontrolled confounding variable has been identified in many of these trials that questions the generalizability of the outcomes: the high prevalence of strongyloidiasis species in regions where some of the studies were conducted. This meta-analysis investigated whether COVID-19 mortality in ivermectin trials was associated with the regional prevalence of strongyloidiasis. There were 12 randomized controlled trials included in the analysis (4 trials in areas of high strongyloidiasis prevalence [> 8.1%], 8 trials in areas of low strongyloidiasis prevalence [<8.1%]). Areas with low regional prevalence demonstrated no significant decrease in the risk of mortality with ivermectin treatment (relative risk [RR]: 0.4 [95% CI: 0.60-1.18]; p= 0.31); in contrast, areas with high regional prevalence resulted in reduced mortality risk among ivermectin-treated patients (RR: 0.25 [95% CI: 0.09-0.70]; p= 0.008). Subgroup differences showed a significant difference between the results of studies in high versus low strongyloidiasis prevalence. Meta-regression analysis demonstrated an association between strongyloidiasis prevalence and mortality risk, with a 38.83% (95% CI: 0.87-62.25) decrease in RR for every 5% increase in strongyloidiasis prevalence. Overall, this study suggests that the benefits of ivermectin treatment for COVID-19 were associated with the regional prevalence of strongyloidiasis. A limitation of this study, however, is that many of the included studies had unclear risk of biases which can be concerning considering that some ivermectin trials conducted were widely believed to have committed ethical violations. Nonetheless, this study informs us that it is imperative to consider this confounder when analyzing ivermectin trials for COVID-19 treatment.

Click to read the study in JAMA Network Open

Relevant Reading: Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines

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