《细胞》子刊：高血糖使免疫细胞变成新冠病毒帮凶！

明河素月

科学家发现，高血糖环境会加速单核/巨噬细胞中新冠病毒复制，并抑制T细胞抗病毒免疫


在近期的《细胞·代谢》上，巴西科学家发表的一篇论文显示，不少“傻白甜”的免疫细胞，可能会被新冠病毒利用：新冠病毒损伤肺部后，聚集到损伤部位的单核/巨噬细胞，可能会在高血糖环境下被新冠病毒利用，变成病毒“制造厂”！

这项研究发现，由于肺部损伤导致的干扰素释放、高血糖影响等原因，单核/巨噬细胞的血管紧张素转换酶2（ACE2）表达会升高，从而更容易被新冠病毒感染。

这些免疫细胞被感染后，会发生代谢重编程，供能主要依靠糖酵解，这不仅使免疫细胞释放更多的IL-6等炎症介质，增加细胞因子风暴的发生风险，还会加速免疫细胞内的病毒复制，同时还能抑制T细胞的抗病毒免疫作用[1]。

已经有大量的临床证据提示，糖尿病或血糖升高，与新冠患者重症和死亡风险显著上升有关，最近《柳叶刀·糖尿病与内分泌学》还专门发表综述，更全面地分析了高血糖的影响[2]。

大多数专家都认为，糖尿病或血糖升高患者的危险系数高，是因为他们往往合并有高血压、肥胖、心血管疾病等各种各样的基础健康问题，而新冠病毒的来袭是火上浇油，把这些问题进一步放大，从而使患者的预后更差。


（图片来源：Lancet Diabetes & Endocrinology）

在胰岛β细胞表面，同样有着新冠病毒可结合的ACE2受体，因此一些原本没有糖尿病的患者，在新冠肺炎发病后出现了糖尿病症状，甚至进入严重的糖尿病酮症酸中毒状态。而二甲双胍等降糖药的使用，可能与患者死亡风险下降有关[3-4]。

但是这些影响，都是新冠病毒对糖尿病和血糖升高的“单向输出”。那么糖尿病和血糖升高，会不会也给新冠病毒反向助攻了一波，让它们更容易兴风作浪呢？

进行本次研究的巴西科学家团队注意到，在被新冠病毒感染后，患者的肺部免疫特征包括了单核/巨噬细胞的明显聚集，因此决定首先分析这些细胞发生的改变。基因测序结果显示，这些细胞都存在干扰素通路相关基因表达的明显上调。

肺部细胞被病毒伤害，就释放细胞因子招募来单核/巨噬细胞，然后免疫细胞启动干扰素通路，这是很正常的。但研究团队同时也发现，干扰素会使聚集来的单核/巨噬细胞表面ACE2表达升高，这相当于直接把破绽暴露给了新冠病毒！

而在被新冠病毒感染后，单核/巨噬细胞就会释放更多的TNF-β、IL-1β、IL-6等促炎性的细胞因子，这可绝对不妙，毕竟释放多了，要命的细胞因子风暴就来了。


（与正常状态（Mock）相比，被感染的单核/巨噬细胞内病毒负荷更高，释放的促炎性细胞因子也更多）

研究团队在不同血糖浓度下进行的培养显示，单核/巨噬细胞表面的ACE2表达水平，分泌IL-1β量的高低，以及细胞内的病毒负荷水平，都与培养基中的血糖浓度正相关。

换句话说，新冠肺炎患者如果血糖升高，体内的单核/巨噬细胞就更容易被新冠病毒感染，促进炎症反应的效果也更强，这和研究团队从患者体内直接提取细胞分析的结论一致。毕竟合成病毒是个消耗能量的活儿，对血糖需求多也正常嘛。


（血糖高了，ACE2和IL-1β就跟着高）


而在被新冠病毒感染后，单核/巨噬细胞会发生明显的代谢重编程，供能切换到以糖酵解为主，这是本次研究中发现的专属于新冠病毒的“招牌动作”。H1N1流感病毒或呼吸道合胞病毒（RSV）感染，都不会出现类似的情况。

进一步的实验显示，通过糖酵解代谢葡萄糖，是新冠病毒在单核/巨噬细胞内复制的必要条件。糖酵解的整个过程中，由细胞线粒体活性氧调控的HIF-1α起着关键作用，因此研究团队提出，靶向HIF-1α可能在新冠肺炎的治疗中有一定价值。

被感染的单核/巨噬细胞，还不止是病毒和促炎性细胞介质的加工厂，这些猪队友/神对手，甚至会通过其它途径助纣为虐。

研究团队发现，被感染单核/巨噬细胞分泌的IL-1β，能抑制CD4+/CD8+T细胞的增殖，同时T细胞表面的PD-1表达会明显上升，提前进入耗竭状态，不能参与抗病毒免疫。而且被感染的单核/巨噬细胞，甚至能直接诱导肺部上皮细胞凋亡！


（一张图总结猪队友/神对手的斑斑劣迹）




参考资料：
1.Codo A C, Davanzo G G, Monteiro L D B, et al. Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis [J]. Cell Metabolism, 2020.
2.Apicella M, Campopiano M C, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes[J]. The Lancet Diabetes & Endocrinology, 2020.
3.Chee Y J, Ng S J H, Yeoh E. Diabetic ketoacidosis precipitated by Covid-19 in a patient with newly diagnosed diabetes mellitus[J]. Diabetes Research and Clinical Practice, 2020.
4.https://www.medrxiv.org/content/10.1101/2020.06.19.20135095v2

明河素月

抗疫战斗中还要加一条：不要胡吃海喝，特别是要少吃点糖和碳水！

坚持健康饮食是对的，高血糖给新冠病毒当帮凶，简直就跟促癌机制差不多了……

猪胖胖

每个字我都认识，放一起就不懂了
谢谢二楼的金句总结

lxk

糖尿病，高血糖人群对新冠状病毒感染的易感性和病程的确很不一样。糖尿病人还是要特别小心的！

datou1981

我还是努力吃肉

明河素月

猪胖胖 发表于 2020-8-1 10:27
每个字我都认识，放一起就不懂了
谢谢二楼的金句总结

我也是啊，能看懂结论就行

waterfish

这个世界对糖尿病患者太不友好

yumintaoaud

不去研究羟基氯喹 成天搞些这些没用的

明河素月

lxk 发表于 2020-8-1 11:15
糖尿病，高血糖人群对新冠状病毒感染的易感性和病程的确很不一样。糖尿病人还是要特别小心的！ ...

对的，而且没有糖尿病史的新冠患者也会出现糖尿病症状。
所以真不能掉以轻心，不要觉得得就得了，大号流感没什么，新冠病毒的危害远超想象

明河素月

datou1981 发表于 2020-8-1 11:21
我还是努力吃肉

甜食的诱惑实在太大

明河素月

waterfish 发表于 2020-8-1 11:45
这个世界对糖尿病患者太不友好

这个病毒对人类全体都不友好.....

stmimi

科普知识，很有帮助。 辛苦了。

myangaus

翻译辛苦了

myangaus

还看到服用降胆固醇药对新冠病毒有抑制作用

astina

所以英国首相在全国推广健康生活方式，胖人要少吃糖减肥

不太可能

myangaus 发表于 2020-8-1 23:35
还看到服用降血压对新冠病毒有抑制作用

降压药应该可以维持血管的压力吧。

明河素月

myangaus 发表于 2020-8-1 23:33
翻译辛苦了

转贴，不辛苦....

明河素月

astina 发表于 2020-8-1 23:36
所以英国首相在全国推广健康生活方式，胖人要少吃糖减肥

少吃糖，少吃碳水，吃惯米饭的人觉得好难啊

明河素月

stmimi 发表于 2020-8-1 12:24
科普知识，很有帮助。 辛苦了。

谢谢！虽然一直知道三高不好，但是看到此文还是挺吃惊的，有些饮食习惯必须要改一下了

明河素月

myangaus 发表于 2020-8-1 23:35
还看到服用降血压对新冠病毒有抑制作用

有具体文章分享一下吗？

moody

还据说vd缺乏的新冠患者死亡率高。

myangaus

明河素月 发表于 2020-8-2 00:12
有具体文章分享一下吗？

疫情下不断有新发现

此外，以色列还有研究发现，降胆固醇常用药或有助治疗新冠肺炎。


以色列耶路撒冷希伯来大学雅各布·纳哈米阿斯教授领导的研究小组称，他们完成的早期研究显示，降胆固醇药物非诺贝特在实验室研究中能抑制新冠病毒的复制，可能有助于治疗新冠患者。


不好意思，记错了

明河素月

moody 发表于 2020-8-2 00:51
还据说vd缺乏的新冠患者死亡率高。

是吗？有文章看看吗？
补充VD倒是不难:)

astina

明河素月 发表于 2020-8-2 00:02
少吃糖，少吃碳水，吃惯米饭的人觉得好难啊

生活习惯是慢慢改的，不能一蹴而就，先减少米饭增加粗粮

myangaus

最近吃零食特别多，糖果也吃的多了。三月份听医生的建议买了锌片服用。

moody

明河素月 发表于 2020-8-2 08:49
是吗？有文章看看吗？
补充VD倒是不难:)

Science Newsfrom research organizations
Vitamin D levels appear to play role in COVID-19 mortality rates
Patients with severe deficiency are twice as likely to experience major complications
Date:
May 7, 2020
Source:
Northwestern University
Summary:
Researchers analyzed patient data from 10 countries. The team found a correlation between low vitamin D levels and hyperactive immune systems. Vitamin D strengthens innate immunity and prevents overactive immune responses. The finding could explain several mysteries, including why children are unlikely to die from COVID-19.
Share:
   
FULL STORY
After studying global data from the novel coronavirus (COVID-19) pandemic, researchers have discovered a strong correlation between severe vitamin D deficiency and mortality rates.
Led by Northwestern University, the research team conducted a statistical analysis of data from hospitals and clinics across China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom (UK) and the United States.

The researchers noted that patients from countries with high COVID-19 mortality rates, such as Italy, Spain and the UK, had lower levels of vitamin D compared to patients in countries that were not as severely affected.

This does not mean that everyone -- especially those without a known deficiency -- needs to start hoarding supplements, the researchers caution.

"While I think it is important for people to know that vitamin D deficiency might play a role in mortality, we don't need to push vitamin D on everybody," said Northwestern's Vadim Backman, who led the research. "This needs further study, and I hope our work will stimulate interest in this area. The data also may illuminate the mechanism of mortality, which, if proven, could lead to new therapeutic targets."

The research is available on medRxiv, a preprint server for health sciences.

Backman is the Walter Dill Scott Professor of Biomedical Engineering at Northwestern's McCormick School of Engineering. Ali Daneshkhah, a postdoctoral research associate in Backman's laboratory, is the paper's first author.

Backman and his team were inspired to examine vitamin D levels after noticing unexplained differences in COVID-19 mortality rates from country to country. Some people hypothesized that differences in healthcare quality, age distributions in population, testing rates or different strains of the coronavirus might be responsible. But Backman remained skeptical.

"None of these factors appears to play a significant role," Backman said. "The healthcare system in northern Italy is one of the best in the world. Differences in mortality exist even if one looks across the same age group. And, while the restrictions on testing do indeed vary, the disparities in mortality still exist even when we looked at countries or populations for which similar testing rates apply.

"Instead, we saw a significant correlation with vitamin D deficiency," he said.

By analyzing publicly available patient data from around the globe, Backman and his team discovered a strong correlation between vitamin D levels and cytokine storm -- a hyperinflammatory condition caused by an overactive immune system -- as well as a correlation between vitamin D deficiency and mortality.

"Cytokine storm can severely damage lungs and lead to acute respiratory distress syndrome and death in patients," Daneshkhah said. "This is what seems to kill a majority of COVID-19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system."

This is exactly where Backman believes vitamin D plays a major role. Not only does vitamin D enhance our innate immune systems, it also prevents our immune systems from becoming dangerously overactive. This means that having healthy levels of vitamin D could protect patients against severe complications, including death, from COVID-19.

"Our analysis shows that it might be as high as cutting the mortality rate in half," Backman said. "It will not prevent a patient from contracting the virus, but it may reduce complications and prevent death in those who are infected."

Backman said this correlation might help explain the many mysteries surrounding COVID-19, such as why children are less likely to die. Children do not yet have a fully developed acquired immune system, which is the immune system's second line of defense and more likely to overreact.

"Children primarily rely on their innate immune system," Backman said. "This may explain why their mortality rate is lower."

Backman is careful to note that people should not take excessive doses of vitamin D, which might come with negative side effects. He said the subject needs much more research to know how vitamin D could be used most effectively to protect against COVID-19 complications.

"It is hard to say which dose is most beneficial for COVID-19," Backman said. "However, it is clear that vitamin D deficiency is harmful, and it can be easily addressed with appropriate supplementation. This might be another key to helping protect vulnerable populations, such as African-American and elderly patients, who have a prevalence of vitamin D deficiency."

Backman is the director of Northwestern's Center for Physical Genomics and Engineering and the associate director for Research Technology and Infrastructure at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.

moody

明河素月 发表于 2020-8-2 08:49
是吗？有文章看看吗？
补充VD倒是不难:)

伊丽莎白女王医院（Queen Elizabeth Hospital）基金会和东英吉利大学（University of East Anglia）的科学家确定了在某些国家新冠病毒死亡率高和维生素D摄入水平低的关系，发现身体中缺乏这种维生素的人最容易感染COVID-19病毒。
研究：西班牙科学家发现新冠病毒感染的5种皮肤表现
© REUTERS / SERGIO PEREZ
研究：西班牙科学家发现新冠病毒感染的5种皮肤表现
科学家的初步研究已被发表在“研究广场”公司（Research Square）的网站上，他们将20多个欧洲国家公民的维生素D摄入水平与新冠病毒导致的死亡率数据进行了对比。
在研究报告中称，“我们发现，维生素D摄入水平与COVID-19病毒病例数量、尤其这种感染性疾病导致的死亡率之间存在明显关联。最容易感染新冠病毒的人群也是最缺乏维生素D的人群。”

研究报告指出，老年人中体内的维生素D含量低，尤其在西班牙、意大利和瑞士这些国家。研究人员补充称，“这些国家的新冠病毒感染病例最多，而老年人是严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2，即新冠肺炎病毒）发病率和死亡率最高的群体。”

科学家们强调，“我们认为，我们可以推荐人们补充维生素D，从而抵御新冠病毒感染。”

moody

明河素月 发表于 2020-8-2 00:12
有具体文章分享一下吗？

我看到过这个说法，所以坚定了每天一颗vd。找了下来源，可以参考。

ACLWOW

明河素月

moody 发表于 2020-8-3 08:23
伊丽莎白女王医院（Queen Elizabeth Hospital）基金会和东英吉利大学（University of East Anglia）的科 ...

有道理！我想到老人院的那些老人，估计不容易晒到太阳，也不会特别补充VD，所以特别容易中招