Metformin therapy in COVID-19: inhibition of NETosis
Abstract
1 3 their counterparts randomized to placebo (odds ratio = 1.05; 95% confidence interval 0.71 to 1.56). In addition, the mortality rate was not significantly different between the metformin group and the placebo group (3.3% versus 4.4%; P = 0.53). It is worthwhile to discuss the discrepancy in the findings with metformin therapy in patients with COVID-19 between real-life observational studies and randomized trial to avoid hampering further enthusiasm to investigate the efficacy of metformin therapy in this population of patients. We believe the discrepancy may be attributable to that the main driver of clinical benefits with metformin in COVID19 is the ability of metformin to inhibit the formation of neutrophil extracellular trap (NET) induced by SARS-CoV-2, but not its anti-inflammatory activities [4]. Recently, it has been reported in patients with COVID-19 that, persistent elevations in NETs post-disease diagnosis were detected in those who were symptomatic, but not in their counterparts who were asymptomatic [5]. Therefore, NET formation is an important determinant of clinical severity in this population of patients. Patients with COVID-19 also displayed impaired NET degradation, which leads to the persistence of symptoms [5]. Moreover, NETs were detected in many organs of adult patients who died from COVID-19 related complications [5]. The findings where pre-diagnosis use of metformin was associated with clinical benefits (in observational studies [1, 2]) may be due to…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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