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2021年12月15日：香港大学医学院：奥密克戎变异株比德尔塔更快更易感染人类支气管，但肺部的感染较轻
由香港大学李嘉诚医学院的研究人员领导的一项研究，首次提供了关于新冠新型关切变异株（VOC）——奥密克戎——如何感染人类呼吸道的信息。研究人员发现，奥密克戎感染人类支气管的速度比德尔塔变异株和原始的新冠毒株快了 70 倍，这可能解释了为什么奥密克戎在人与人之间的传播速度比以前的变异株快。他们的研究还显示，奥密克戎造成的肺部感染明显低于原始的新冠毒株，这个指标可能说明疾病的严重程度较低。这项研究目前正在接受同行评议，待发表。香港科技园公共卫生学院副教授及免疫及感染研究中心首席研究员陈智威（Chan Chi-wai）博士，以及香港大学医学院病理科教授John Nicholls教授，自 2007 年起率先使用体外呼吸道培养，来调查许多新出现的病毒感染，例如禽流感、中东呼吸综合征(MERS)的冠状病毒等。现在，他们使用这项技术去搞清为什么奥密克戎变异株在传播和疾病严重程度上可能与其他新冠变异株不同。这种方法利用因治疗需被切除的肺组织来调查呼吸道的病毒性疾病，这些组织如不使用则通常会被废弃。陈博士和他的团队成功地分离出了奥密克戎变异株，并使用这个实验模型将感染与 2020 年最初的新冠毒株、德尔塔变异株和最近的奥密克戎进行了比较。他们发现，在人类支气管中，新的奥密克戎变异株比最初的新冠毒株和德尔塔变异株复制得更快。在感染 24 小时后，奥密克戎变异株的复制率比德尔塔变异株和最初的新冠毒株高约70倍。相比之下，奥密克戎变异株在人类肺部组织中的复制效率较低（比最初的新冠毒株低 10 倍以上），这可能意味着疾病的严重程度较低。陈博士说:“值得注意的是，人类疾病的严重程度不仅取决于病毒复制，还取决于宿主对感染的免疫反应，这可能导致先天免疫系统失调，即‘细胞因子风暴’。”“还需要指出的是，一种传染性很强的病毒会感染更多的人，从而导致更严重的疾病和死亡，尽管这种病毒本身的致病性可能较低。”因此，结合我们最近的研究表明，奥密克戎变异株可以部分逃脱疫苗和过去感染的免疫，奥密克戎变异株的总体威胁可能非常重大。”
2022 年 1 月 5 日：《自然》：奥密克戎对肺部的弱攻击可能会降低它的危险性
动物研究中越来越多的证据表明，奥密克戎在肺组织中不易繁殖，而在感染其他变异株的人身上，肺组织可能会受到严重破坏。
来自南非和英国的初步迹象表明，快速传播的新冠奥密克戎变异株相较之前的德尔塔，危险性较小。现在，一系列的实验室研究为这种差异提供了一个说得通的解释：奥密克戎感染肺部深处的细胞，并不会像它感染上呼吸道那样容易。“这是一个非常有吸引力的观察结果，或许可以解释我们在病人身上看到的现象，”加州旧金山格莱斯顿病毒学研究所的病毒学家 Melanie Ott 说。她没有参与这项研究。但是她补充说：奥密克戎的高度传染性意味着医院很快就会人满为患——尽管它所导致的疾病的严重程度有所降低。南非当局于 12 月 30 日宣布，该国已度过奥密克戎高峰，死亡人数没有出现大幅上升。英国政府 12 月 31 日的一份报告说，在英格兰，因感染奥密克戎病毒而需要住院治疗或紧急护理的人的比例，约为感染德尔塔病毒的人的一半。但是，通过疫苗接种、感染或通过两者同时获得新冠免疫保护的人数，随着时间的推移而增加，这使得很难确定奥密克戎是否在本质上比早期的变异株更温和，导致的病症更轻。为了找到答案，研究人员将目光转向了动物和实验室培养皿中的细胞。密苏里州圣路易斯华盛顿大学的病毒学家 Michael Diamond 和他的同事们用奥密克戎和其他新冠变异株感染仓鼠和小鼠，以跟踪疾病的发展。这种差异是惊人的：几天后，感染奥密克戎的动物，肺部的病毒浓度至少比感染其他变异株的啮齿动物低 10 倍。其他团队也注意到，与之前的变异株相比，奥密克戎在肺组织中的水平降低了。Diamond说：他特别震惊地看到，被奥密克戎感染的动物体重并没有变化，而其他动物的体重却迅速下降，后者表明感染导致了严重的疾病。“之前的每种新冠毒株都很容易感染仓鼠，感染程度很高。但很明显，奥密克戎对仓鼠来说是不同的。肺部是冠状病毒造成大部分损害的地方，肺部感染可以引发炎症性免疫反应，破坏受感染和未受感染的细胞，导致组织瘢痕化和缺氧。受感染的肺细胞越少，表明病症较轻。”另一个研究小组发现：在感染肺细胞和被称为有机物的微型肺模型方面，奥密克戎的成功程度远不如之前的变异株。这些实验还发现了一个可能的原因：一种名为 TMPRSS2 的蛋白质，它突出在肺部和其他器官的许多细胞表面，但在大多数鼻和喉咙细胞的表面明显缺失。之前的变异株已经利用这种蛋白质来感染细胞，但研究人员注意到奥密克戎不能与 TMPRSS2 很好地结合。相反，它往往会在被细胞摄取时进入细胞。奥密克戎更容易感染上呼吸道
英国剑桥大学病毒学家 Ravindra Gupta 是 TMPRSS2 研究的合著者之一。他表示：难以进入肺细胞，可能有助于解释为什么奥密克戎更容易引发上呼吸道感染，而不是肺部感染。Gupta说，这个理论也可以解释，为什么根据一些估计，奥密克戎的传染性几乎和麻疹一样，而麻疹是高传染性的基准。如果变异株停留在上呼吸道，病毒颗粒可能会很容易“搭乘”从鼻子和嘴巴排出的物质，从而让病毒找到新的宿主。其他数据提供了直接证据，表明奥密克戎在上呼吸道比在肺部更容易复制。
Ott说，最新的结果可能意味着“病毒在上呼吸道形成了非常局部的感染，在肺部造成严重破坏的机会更少”。这将是一个令人高兴的消息。但是宿主的免疫反应在疾病的严重程度中扮演着重要的角色，如果科学家们想要了解奥密克戎的基本生物性如何影响其在人类中的疾病进展，他们需要更多的临床数据。
2022 年 1 月 8 日：奥密克戎是“大号流感”？张文宏：不是！它会咬人https://www.shantou.gov.cn/stswsj/gkmlpt/content/2/2014/post_2014378.html#3521
感染新冠病毒奥密克戎变异株后，生命健康受到的影响有多大？1月8日，国家传染病医学中心主任、复旦大学附属华山医院感染科主任张文宏表示，一些自媒体说奥密克戎引发的是“大号流感”，这是缺乏科学依据的，他研究奥密克戎感染者的医学影像后认为，这种变异株“会咬人”。一个国家和地区需要强大的免疫屏障和医疗资源，才能抵御奥密克戎的威胁。“今天上午8点半，我还轻轻抚摸过奥密克戎的片子。”张文宏告诉听众，“自媒体说这个变异株引起的是‘大号流感’，这是不足为据的，我们复旦校友可不要人云亦云。”据介绍，奥密克戎是新冠病毒在人体免疫压力下的自然选择结果，“可以说，奥密克戎在与免疫系统斗争后赢了”。目前，这种首先在南非发现的变异株已肆虐全球，导致很多国家和地区的感染人数大幅上升。张文宏认为，西方国家之所以在“硬闯”这波疫情，其底气主要来自疫苗，其效果有待进一步评估。目前，美国的新冠疫苗接种率接近70%，三针疫苗接种率是22%，所以大多数健康的年轻人有望平安“闯”过这波疫情，但免疫力低下的人群呢？前景不容乐观。英国近期每天新增确诊人数超过20万，但病死率没有明显上升。究其原因，是英国的新冠疫苗接种率达到80%，三针疫苗接种率超过50%，且尚未出现严重的医疗资源挤兑情况。在亚洲，新加坡的两针及以上新冠疫苗接种率高达90%以上，目前病死率控制在非常低的水平。以色列近期每天新增确诊人数超过1万，但病死率也非常低，其主要原因也是疫苗接种率高，三针接种率达到50%。以色列政府规定，60岁以上老年人必须接种第三针疫苗。“我们允许关于疫苗接种的争论，但要看到，疫苗在新冠疫情防控中的作用是不可低估的。”张文宏说，“如果我们不积极接种疫苗，筑起强大的免疫屏障，就会回到1918年那次全球疫情。”在他看来，虽然疫苗屏障没有完全防住新冠病毒的传播，但它已让病毒的毒性大幅下降，降低了感染者的病死率。除了不断提高疫苗两针及以上的接种率，一个国家或地区还要确保医疗资源的充分供给，这样才能对免疫力低下的感染者进行充分救治。“如果医疗资源不够，奥密克戎是会‘咬人’的。”张文宏说，“我国各地都要确保医疗资源的充分和平等。”在演讲结束前，他表示，“已看到漫漫长夜的曙光。世界何时重新开放？一是要筑起强大的免疫屏障，二是把病死率控制得很低。”
http://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infectionHKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lungA study led by researchers from the LKS Faculty of Medicine at The University of Hong Kong (HKUMed) provides the first information on how the novel Variant of Concern (VOC) of SARS-CoV-2, the Omicron SARS-CoV-2 infect human respiratory tract. The researchers found that Omicron SARS-CoV-2 infects and multiplies 70 times faster than the Delta variant and original SARS-CoV-2 in human bronchus, which may explain why Omicron may transmit faster between humans than previous variants. Their study also showed that the Omicron infection in the lung is significantly lower than the original SARS-CoV-2, which may be an indicator of lower disease severity. This research is currently under peer review for publication.Dr Michael Chan Chi-wai, Associate Professor of School of Public Health and Principal Investigator, Centre for Immunology and Infection (C2i), Hong Kong Science and Technology Park (HKSTP) and Professor John Nicholls, Professor of Department of Pathology, HKUMed have pioneered the use of ex vivo cultures of the respiratory tract for investigating many emerging virus infections since 2007, such as avian influenza, coronavirus of the Middle East Respiratory Syndrome (MERS). Now this technique has been applied to understand why the Omicron variant may differ in transmission and disease severity from other SARS-CoV-2 variants.This method uses lung tissue removed for treatment of the lung, which is normally discarded, for investigating virus diseases of the respiratory tract. Dr Chan and his team successfully isolated the Omicron SARS-CoV-2 variant and used this experimental model to compare infection with the original SARS-CoV-2 from 2020, the Delta variant and the recent Omicron variant. They found that the novel Omicron variant replicates faster than the original SARS-CoV-2 virus and Delta variant in the human bronchus. At 24 hours after infection, the Omicron variant replicated around 70 times higher than the Delta variant and the original SARS-CoV-2 virus. In contrast, the Omicron variant replicated less efficiently (more than 10 times lower) in the human lung tissue than the original SARS-CoV-2 virus, which may suggest lower severity of disease.‘It is important to note that the severity of disease in humans is not determined only by virus replication but also by the host immune response to the infection, which may lead to dysregulation of the innate immune system, i.e. “cytokine storm”,’ said Dr Chan. ‘It is also noted that, by infecting many more people, a very infectious virus may cause more severe disease and death even though the virus itself may be less pathogenic. Therefore, taken together with our recent studies showing that the Omicron variant can partially escape immunity from vaccines and past infection, the overall threat from Omicron variant is likely to be very significant.’https://www.nature.com/articles/d41586-022-00007-8Omicron's feeble attack on the lungs could make it less dangerousMounting evidence from animal studies suggests that Omicron does not multiply readily in lung tissue, which can be badly damaged in people infected with other variants.Early indications from South Africa and the United Kingdom signal that the fast-spreading Omicron variant of the coronavirus SARS-CoV-2 is less dangerous than its predecessor Delta. Now, a series of laboratory studies offers a tantalizing explanation for the difference: Omicron does not infect cells deep in the lung as readily as it does those in the upper airways.“It’s a very attractive observation that might explain what we see in patients,” says Melanie Ott, a virologist at the Gladstone Institute of Virology in San Francisco, California, who was not involved in the research. But she adds that Omicron’s hyper-transmissibility means that hospitals are filling quickly — despite any decrease in the severity of the disease it causes.Authorities in South Africa announced on 30 December that the country had passed its Omicron peak without a major spike in deaths. And a 31 December UK government report said that people in England who were infected with Omicron were about half as likely to require hospitalization or emergency care as were those infected with Delta.But the number of people who have gained immune protection against COVID-19 through vaccination, infection or both has grown over time, making it difficult to determine whether Omicron intrinsically causes milder disease than earlier variants. For answers, researchers have turned to animals and to cells in laboratory dishes.How the coronavirus infects cells — and why Delta is so dangerous
Michael Diamond, a virologist at Washington University in St. Louis, Missouri, and his colleagues infected hamsters and mice with Omicron and other variants to track disease progression. The differences were staggering: after a few days, the concentration of virus in the lungs of animals infected with Omicron was at least ten times lower than that in rodents infected with other variants1. Other teams have also noted that compared with previous variants, Omicron is found at reduced levels in lung tissue2,3.
Diamond says he was especially shocked to see that the Omicron-infected animals nearly maintained their body weight, whereas the others quickly lost weight — a sign that their infections were causing severe disease. “Every strain of SARS-CoV-2 has infected hamsters very easily, to high levels,” he says, “and it’s clear that this one is different for hamsters.” The lungs are where the coronavirus does much of its damage, and lung infection can set off an inflammatory immune response that ravages infected and uninfected cells alike, leading to tissue scarring and oxygen deprivation. Fewer infected lung cells could mean milder illness.Another group found that Omicron is much less successful than previous variants at infecting lung cells and miniature lung models called organoids4. These experiments also identified a plausible player in the difference: a protein called TMPRSS2, which protrudes from the surfaces of many cells in the lungs and other organs, but is notably absent from the surfaces of most nose and throat cells.Previous variants have exploited this protein to infect cells, but the researchers noticed that Omicron doesn’t bind to TMPRSS2 so well. Instead, it tends to enter cells when it is ingested by them5,6.Upper airway preferred
Difficulty entering lung cells could help to explain why Omicron does better in the upper airways than in the lungs, says Ravindra Gupta, a virologist at the University of Cambridge, UK, who co-authored one of the TMPRSS2 studies4. This theory could also explain why, by some estimates, Omicron is nearly as transmissible as measles, which is the benchmark for high transmissibility, says Diamond. If the variant lingers in the upper airways, viral particles might find it easy to hitch a ride on material expelled from the nose and mouth, allowing the virus to find new hosts, says Gupta. Other data provide direct evidence that Omicron replicates more readily in the upper airways than in the lungs2,5.
The latest results could mean that “the virus establishes a very local infection in the upper airways and has less chance to go and wreak havoc in the lungs”, Ott says. That would be welcome news — but a host’s immune response plays an important part in disease severity, and scientists need more clinical data if they are to understand how Omicron’s basic biology influences its disease progression in humans.Omicron’s course of infection could also have implications for children, says Audrey John, a specialist in paediatric infectious disease at the Children’s Hospital of Philadelphia in Pennsylvania. Young children have relatively small nasal passages, and babies breathe only through their noses. Such factors can make upper respiratory conditions more serious for children than for adults, John says. But she adds that she has not seen data suggesting an uptick in the numbers of young children hospitalized for croup and other conditions that could indicate a severe infection of the upper respiratory tract.Although there is still much to learn about the new variant, Gupta says that fears raised in late November by the multitude of mutations in Omicron’s genome have not been completely borne out. He says the initial alarm offers a cautionary tale: it’s difficult to predict how a virus will infect organisms from its genetic sequence alone.doi: https://doi.org/10.1038/d41586-022-00007-81.Diamond, M. et al. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-1211792/v1 (2021).2.McMahan, K. et al. Preprint at bioRxiv https://doi.org/10.1101/2022.01.02.474743 (2022).3.Bentley, E. G. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.12.26.474085 (2021).4.Meng, B. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.12.17.473248 (2021).5.Peacock, T. P. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.12.31.474653 (2022).6.Willett, B. J. et al. Preprint at medRxiv https://doi.org/10.1101/2022.01.03.21268111 (2022).