Pathological signaling in the lung induced by particulate matter (PM) air pollution partially overlaps with that provoked by COVID-19, the pandemic disease caused by infection with the novel coronavirus SARS-CoV-2. Metformin is capable of suppressing one of the molecular triggers of the proinflammatory and prothrombotic processes of urban PM air pollution, namely the mitochondrial ROS/Ca²⁺ release-activated Ca²⁺ channels (CRAC)/IL-6 cascade. Given the linkage between mitochondrial functionality, ion channels, and inflamm-aging, the ability of metformin to target mitochondrial electron transport and prevent ROS/CRAC-mediated IL-6 release might illuminate new therapeutic avenues to quell the raging of the cytokine and thrombotic-like storms that are the leading causes of COVID-19 morbidity and mortality in older people. The incorporation of infection rates, severity and lethality of SARS-CoV-2 infections as new outcomes of metformin usage in elderly populations at risk of developing severe COVID-19, together with the assessment of bronchial/serological titers of inflammatory cytokines and D-dimers, could provide a novel mechanistic basis for the consideration of metformin as a therapeutic strategy against the inflammatory and thrombotic states underlying the gerolavic traits of SARS-CoV-2 infection.

中文翻译：

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二甲双胍和 SARS-CoV-2：关于空气污染抵御 COVID-19 细胞因子/血栓风暴的机制教训。

由颗粒物 (PM) 空气污染引起的肺部病理信号与由新型冠状病毒 SARS-CoV-2 感染引起的流行性疾病 COVID-19 引起的病理信号部分重叠。二甲双胍能够抑制城市 PM 空气污染的促炎和促血栓形成过程的分子触发因素之一，即线粒体 ROS/Ca ²⁺释放激活的 Ca ²⁺通道 (CRAC)/IL-6 级联。考虑到线粒体功能、离子通道和炎症衰老之间的联系，二甲双胍靶向线粒体电子传递和阻止 ROS/CRAC 介导的 IL-6 释放的能力可能会阐明新的治疗途径，以平息细胞因子和血栓形成的肆虐。像暴风雨一样，它们是老年人 COVID-19 发病和死亡的主要原因。将 SARS-CoV-2 感染的感染率、严重程度和致死率纳入有发展为严重 COVID-19 风险的老年人群中使用二甲双胍的新结果，同时评估炎症细胞因子和 D-二聚体的支气管/血清滴度，可以为考虑二甲双胍作为针对 SARS-CoV-2 感染的 gerolavic 特征的炎症和血栓状态的治疗策略提供新的机制基础。