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COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?

新型冠状病毒肺炎和个体遗传易感性/感受性: ACE1/ACE2 基因的作用,免疫,炎症和凝血。与男性的单X染色体相比,女性的双X染色体对SARS-CoV-2 有保护作用吗?

  • 影响因子:4.5560
  • DOI:10.3390/ijms21103474
  • 作者列表:"Gemmati D","Bramanti B","Serino ML","Secchiero P","Zauli G","Tisato V
  • 发表时间:2020-05-14
Abstract

:In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.

摘要

: 在十二月 2019 年,提出了一种新的严重急性呼吸道症候群 (传染性非典型肺炎) 从一个新的冠状病毒 (传染性非典型肺炎-CoV-2) 是公认的在城市武汉,中国.它迅速成为中国的一种流行病,现在已经蔓延到世界各地,达到大流行的程度。高死亡率表征SARS-CoV-2 疾病 (新型冠状病毒肺炎),主要影响老年人,引起不受限制的细胞因子风暴和随后的肺关闭,也怀疑微血栓栓塞事件。目前,没有特定和专门的治疗方法,也没有批准的疫苗,尽管非常有希望的数据来自抗炎、抗疟疾的使用,和抗凝血药物。此外,男性似乎比女性更容易感染SARS-CoV-2,男性死于感染的可能性比女性高 65%。来自世卫组织和中国科学家的数据显示,在所有病例中,大约 1.7% 感染病毒的女性会死亡,而男性的这一比例为 2.8%。香港医院的数据显示,32% 的男性和 15% 的女性新型冠状病毒肺炎患者需要重症监护或死亡。另一方面,由于社会和社会心理原因,冠状病毒的长期沉降物对女性可能比男性更糟糕。无论从世卫组织获得的性别或性别偏见数据以及从有时有争议的科学期刊收集的数据,都应该考虑一些中心点。首先,SARS-CoV-2 与人ACE 2 受体有很强的相互作用,与跨膜丝氨酸蛋白酶 2 (TMPRSS 2) 一起在细胞进入中起重要作用; 有趣的是,ACE 2 基因位于X染色体上,因此,允许女性与绝对半合子的男性相比具有潜在的杂合子和不同的什锦。其次,女性中较高的ACE2 表达率,尽管存在争议,但与世界范围的流行病学数据相比,可能是预后最差的原因。最后,参与炎症的几个基因位于X染色体上,它也包含了大量的免疫相关基因,负责对感染的固有和适应性免疫反应。来自RAS途径的其他基因可能通过影响其主要行为者 (e.g.,ABO基因座,SRY,SOX3,ADAM17)。出乎意料的是,高水平的ACE2 或ACE1/ACE2 再平衡可能通过减少炎症、血栓形成和死亡来改善两性新型冠状病毒肺炎的结局。此外,X杂合女性也可能激活镶嵌优势,表现出更明显的性别相关差异,导致性别二型,进一步有利于她们对抗SARS-CoV-2 感染的进展。

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DOI:10.3346/jkms.2020.35.e79
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.

影响因子:4.36
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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
影响因子:2.48
发表时间:2020-04-01
来源期刊:Infection
DOI:10.1007/s15010-020-01401-y
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.

呼吸道感染方向

呼吸道感染分为上呼吸道感染与下呼吸道感染。上呼吸道感染是指自鼻腔至喉部之间的急性炎症的总称,是最常见的感染性疾病。下呼吸道感染是最常见的感染性疾患,治疗时必须明确引起感染的病原体以选择有效的抗生素。

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