Background: Ivermectin has demonstrated different mechanisms of action that potentially protect from both coronavirus disease 2019 (COVID-19) infection and COVID-19-related comorbidities. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of...
www.cureus.com
The propensity matching was done incorrectly. They created propensity scores for mortality and did not exclude people who were already on ivermectin, but
controlled for it.
This doesn’t make much sense especially given the voluntary prophylactic application. This is very weird trial design and this statistical methodology should be caught in peer review as long as they have someone competent read this
When have you seen observational studies touted by experts when it comes to drugs?! The gold standard is always RCT's. A positive result from observational studies can be a signal to run RCT's, but the conclusion is never "point proven, Q.E.D., game set match" but rather "more research is needed."
One thing I always like to highlight when discussing ivermectin is that
WHO has been recommending ivermectin for COVID patients living or traveling in territories with high strongyloide (parasitic worms) endemicity since 2020. It is my guess that some of the efficacy signals from studies conducted in such territories might be real, even if were magically able to account for all of the weaknesses and limitations in most of these study designs.
By way of background, it was discovered quite early during the COVID pandemic (I'd say before the summer of 2020) that an asymptomatic or mild strongyloide infection can rapidly develop into hyperinfection, a severe disease, when corticosteroids are administered. Corticosteroids are cornerstones of COVID treatment, but since they are immunosuppressive they allow strongyloides to flourish. This is exacerbated by the fact that many areas with widespread strongyloide infection may also have higher prevalence of HTLV-1 infection, which can also trigger rapid progression to hyperinfection. It is quite plausible that ivermectin is effective for patients with concurrent SARS-CoV-2 and strongyloide infections because it kills the strongyloides and prevents hyperinfection (not because of any anti-viral properties of ivermectin).
However, this does
not inform our decision in treating people living in developed territories, where strongyloide infections are not widespread, and the preclinical data supporting ivermectin's supposed "anti-viral" properties is very weak. To date, I have not seen any robust study showing efficacy of ivermectin in treating COVID patients living in developed regions. I'm not saying it won't happen, but it hasn't happened yet. There are some such trials underway, such as ACTIV-6 (US), PRINCIPLE (UK), and COVID-OUT (US). As someone who has been trying to follow ivermectin with an open mind, I'm not too hopeful.
The study contained multiple methodological flaws that call the reliability of its conclusions into question. For example, there are indications that many people assigned to the ivermectin treatment group didn’t take the drug consistently, or stopped taking it after a while. It is therefore unclear whether any observed effect in this group can be reliably attributed to ivermectin treatment.