Metformin and SARS-CoV-2: mechanistic lessons on air pollution to weather the cytokine/thrombotic storm in COVID-19.

二甲双胍和SARS-CoV-2: 空气污染应对新型冠状病毒肺炎细胞因子/血栓风暴的机制教训。

  • 影响因子:4.8310
  • DOI:10.18632/aging.103347
  • 作者列表:"Menendez JA
  • 发表时间:2020-05-27

: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.


颗粒物 (PM) 空气污染引起的肺部病理信号与新型冠状病毒肺炎引起的疾病部分重叠,新型冠状病毒是由SARS-CoV-2 感染引起的大流行性疾病。二甲双胍能够抑制城市PM空气污染的促炎症和促血栓形成过程的分子触发因素之一,即线粒体ROS/Ca2 + 释放激活的Ca2 + 通道 (CRAC)/IL-6 层叠。鉴于线粒体功能、离子通道和炎症老化之间的联系,二甲双胍靶向线粒体电子转运和阻止ROS/CRAC介导的IL-6 释放的能力可能会为平息主要原因的细胞因子和血栓样风暴提供新的治疗途径新型冠状病毒肺炎老年人的发病率和死亡率。将SARS-CoV-2 感染的感染率、严重程度和致死率纳入二甲双胍用于有发生严重新型冠状病毒肺炎风险的老年人群的新结局,与炎症细胞因子和D-二聚体的支气管/血清学滴度评估一起,为考虑二甲双胍作为治疗SARS-CoV-2 感染的炎症和血栓状态提供了新的机制基础。



作者列表:["Lim J","Jeon S","Shin HY","Kim MJ","Seong YM","Lee WJ","Choe KW","Kang YM","Lee B","Park SJ"]

METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

作者列表:["Zhang W","Du RH","Li B","Zheng XS","Yang XL","Hu B","Wang YY","Xiao GF","Yan B","Shi ZL","Zhou P"]

METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

翻译标题与摘要 下载文献
作者列表:["Cheng ZJ","Shan J"]

METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.