为什么有些人一直说新冠新冠毒性会越来越弱?
233 个回答
谁说的呢？
最近nature reviews microbiology发了一篇很直白的评论。说实话，知乎的网友们是很幸运的，因为早在这篇文章出来之前，类似的观点就一直在被很多从事科学相关工作的知友反复普及。科学界对此应该有相当程度的共识。只是很遗憾，公共传播领域的杂音实在不是科学界可以应付的。
划重点：UNPREDICTABLE无法预测的
开头的黑体字部分这样说
The comparatively milder infections with the Omicron variant and higher levels of population immunity have raised hopes for a weakening of the pandemic. We argue that the lower severity of Omicron is a coincidence and that ongoing rapid antigenic evolution is likely to produce new variants that may escape immunity and be more severe.
翻译：Omicron的相对轻症和人群较高的免疫水平引发了疫情逐渐减轻的希望。作者认为Omicron的轻症化是一个巧合。未来的持续高速进化可能会产生免疫逃逸和高毒性的变异株。
够直白了吧。
本想摘几段翻译，不过为免断章取义之嫌，下面会全文翻译。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is set for continuous circulation in humans owing to its ease of transmission, waning immunity, antigenic evolution and an array of potential animal reservoirs1. A key question is predicting the epidemiological and clinical parameters of this continuous circulation2and the future population burden of coronavirus disease 2019 (COVID-19).
新冠病毒由于其高传播性、免疫适性、高速变异进化和潜在的动物宿主等特点持续在人群中传播。解决疫情一个关键问题在于预测其流行趋势和临床特征以及未来的防控成本。
The comparatively milder levels of disease produced by Omicron, the most recent variant of concern (VOC), in relation to previous VOCs rekindled a variety of wishful narratives about the epidemiology and evolution of the virus. These ideas range from misconceived and premature theories about ‘harmless’ endemicity3, to expectations that widespread immunity renders epidemic waves safe and to hopes that the virus will evolve to be benign.
Omicron的相对轻症引发了很多关于病毒流行和进化一厢情愿的论述。这些想法从臆造毫无根据的关于“无害化”疫情理论，到大范围免疫终止疫情的期望以及认为病毒会想“良性”方向进化的妄想。
The notion that viruses will evolve to be less virulent to spare their hosts is one of the most persistent myths surrounding pathogen evolution. Unlike viral immune escape and transmissibility, which are under strong evolutionary pressure, virulence is typically a by-product, fashioned by complex interactions between factors in both the host and the pathogen. Viruses evolve to maximize their transmissibility and sometimes this may correlate with higher virulence, for example, if high viral loads promote transmission but also increase severity. If so, pathogens may evolve towards higher virulence. If severity manifests late in infection, only after the typical transmission window, as in SARS-CoV-2, but also influenza virus, HIV, hepatitis C virus and many others, it plays a limited role in viral fitness and may not be selected against. Forecasting virulence evolution is a complex task, and the lower severity of Omicron is hardly a good predictor for future variants. The prospect of future VOCs featuring the potentially disastrous combination of the ability to reinfect due to immune escape along with high virulence is unfortunately very real.
认为病毒会向减毒方向进化并与宿主共存是有关病原体进化影响最持久的迷思之一。与病毒的免疫逃逸和受到强烈进化筛选的传播性不同，毒性是进化的副产品，其机制与宿主与病原之间的复杂互作相关。病毒会向高传播力的方向进化，有时会与高毒性相关。例如，如果高病毒载量促进传播并同时增强了毒性，则病原会向高毒性方向进化。如果感染造成的症状出现较晚，且在传染开始的窗口之后，如新冠、流感、艾滋、丙肝等传染病，毒性对病毒本身的适性作用有限，不会进入选择压力。预测毒性进化是一个复杂的工作，而较低毒性的Omicron很难作为预测未来变异体的依据。不幸的是，由于免疫逃逸造成的重复感染和高毒性造成的灾难性后果是对未来变异体更加真实的预测。
Another common belief banks on widespread vaccine or infection-induced immunity to guarantee mild SARS-CoV-2 infections in the future. This idea, however, ignores a central feature of SARS-CoV-2 biology — antigenic evolution, that is, an ongoing modification of the viral antigenic profile in response to host immune pressures. High rates of antigenic evolution can result in immune escape, that is, reduced capacity of the immune system to prevent reinfection and potentially severe disease thereupon. On a population level, antigenic evolution and escape can increase burden through increasing the rates of reinfections and rates of severe illness (Fig. 1).
另一个迷思是疫苗和感染铸成的免疫屏障可以保证今后的感染都是轻症。然而这个想法忽略了新冠病毒的核心特征之一：抗原进化。也就是说病毒的抗原性受到宿主免疫的选择压，会持续进化。抗原的高速进化会导致免疫逃逸，从而降低免疫系统阻止重复感染和重症率的能力。对社会而言，抗原进化和免疫逃逸就意味着重复感染率和重症率升高。
Omicron demonstrated clearly that SARS-CoV-2 is capable of considerable antigenic escape over a relatively short period of time. The variant features at least 50 amino acid mutations compared with the ancestral Wuhan-Hu-1 reference strain4and is highly antigenically divergent from earlier VOCs5. Its explosive spread in highly immune populations revealed that these mutations enable the variant to easily infect individuals with immunity due to previous infection or vaccination. Genetic divergence is considerable amongst sub-lineages of omicron, and the functional importance of this divergence is being illustrated by the proportional increase of the BA.2 lineage.
Omicron已经清楚地证明新冠病毒可以在相对短的时间内产生可观的免疫逃逸能力。与武汉的原始病毒株相比，Omicron有至少个氨基酸突变，相比早期变异株产生了高度的免疫分化。其在高免疫屏障保护下的人群中爆发性的传播证明这些突变有利于感染具有免疫力的人。Omicron分支间存在相当程度的遗传分化，这些分化造成的影响正在从BA.2的相应恶化中显现。
In September 2020, after an initial period of relative evolutionary stability, SARS-CoV-2 variants with considerable antigenic divergence from the ancestral virus started to emerge6. At least three earlier VOCs, Beta, Gamma and Delta, featured immune escape mutations7, and nothing currently suggests that antigenic evolution will slow down in the future. On the contrary, VOCs are just the tip of the ‘evolutionary iceberg’. Hundreds of SARS-CoV-2 lineages continuously diverge from each other over time and evolutionary theory predicts increasing chances of immune escape variants in the future.
2020年9月，经历了初始阶段相对稳定的进化以后，产生高度免疫分化的变异株开始出现。至少三个早期变异株，Beta，Gamma和Delta存在导致免疫逃逸的突变。没有证据显示抗原相关的进化速度在未来会降低。另一方面，这些变异只是进化的冰山一角。成百上千的变异株持续分化。根据进化的理论，可以预见未来出现免疫逃逸变异株的可能性只会增加。
The adaptive fitness of a virus is suitably quantified by its effective reproduction number (Rt). Rt is the total number of secondary infections that an infectious case generates in the population8. So, the fittest virus is the one that transmits to the highest number of hosts. In a naive population with everyone susceptible, a virus can best achieve this by becoming more infectious. Early VOCs evolved in this way; Alpha, then Delta were each approximately 50% more infectious than their predecessor, each rapidly displacing it on their way to dominance in the population9. In highly immune populations, however, a mere increment in intrinsic infectiousness will contribute relatively little to transmissibility, because the obstacle in this situation is host resistance to infection. Accordingly, as human populations transition to high levels of immunity, SARS-CoV-2 is predicted to increasingly optimize its transmissibility (Rt) through honing its ability to re-infect immune individuals, and less through being highly infectious. Thus, the growing levels of immunity are likely to accelerate the rates of antigenic evolution, raising both the risk of reinfection and potentially the prospect of higher disease severity of reinfections. The rapid spread of Omicron was facilitated by its extraordinary ability to re-infect immune individuals, exemplifying this evolutionary strategy10.
病毒的适性可以用Rt来衡量。Rt是单一病例次生感染的总和。所以适性最强的病毒是可以传给最多宿主的病毒。在没有免疫力的人群中，感染力越强，适性越强。早期的变异株Alpha就是这样进化的。后来Delta的传染性高出一半，迅速取代了其主导地位。然而在高度免疫的人群中，传染性的贡献相对较小。相应的，新冠的传播性会通过重复感染免疫人群来提高Rt。因此提高免疫水平可能会加速免疫逃逸的出现，增加重复感染和重症的机会。Omicron的高速传播就是通过重复感染实现，证明了这种进化策略。
Omicron is the first VOC that is less virulent than other circulating strains and this has been enthusiastically interpreted to be a sign of the approaching end of the pandemic. Yet the lower severity of Omicron is nothing but a lucky coincidence — compared with previous VOCs, the majority of which featured increased virulence, Omicron appears like the exception. Immune escape needs to hit constantly changing targets. Once Omicron infects the majority of individuals, the next variant will need to be as antigenically different from Omicron and previous VOCs as possible to overcome immunity against them. None of the VOCs that previously rose to dominance originated from the prevailing lineage at the time, which will also likely be the case for future VOCs. We know little about the circumstances and processes that generated all the antigenically divergent variants so far, and this makes it hard to predict the timing or antigenic and viral properties of future variants. A more pathogenic future VOC would sweep and replace Omicron along with the features that contribute to its lower severity (preference for upper respiratory tract over pulmonary tissue9, and reduced tendency to induce cell–cell fusion). Molecular clock analysis dated the split of Omicron from other SARS-CoV-2 lineages to more than a year before its epidemic emergence. This hints at the possibility of other, antigenically divergent variants in existence or currently forming that may be yet to emerge.
Omicron是第一个毒性较低的变异株。而这被很多人积极解读为疫情即将终止的征兆。然而Omicron的轻症化只是一个巧合。参照先前毒性增加的变异株，Omicron更像一个例外。免疫逃逸的存在意味着我们需要打击的目标是持续变化的。一旦Omicron感染了大多数人，下一代变异株就要免疫分化得更加彻底。没有任何一个主流变异株是从先前流行的变异株中进化而来的，而这恐怕也会成为未来的趋势。目前为止，我们对免疫分化的变异机制还知之甚少，这也让预测分化方向和速度非常困难。未来毒性更高的变异株可能会横扫全球，取代低毒性的Omicron（其低毒性的原因是偏好上呼吸道而非肺部以及降低细胞融合的能力）。研究发现Omicron从其它分支分化的时间早在一年多以前。这提示已经存在或正在形成的免疫逃逸变异株的潜在危险性（译注：意为流行的突变不一定是新产生的，可能是已经存在的变异株获得了大流行的机会）。
To understand the future burden of COVID-19, besides exploring the relationship between antigenic escape and disease severity, we need to scrutinize the mechanisms generating highly antigenically divergent variants and the circumstances underlying their emergence. This includes studying patterns of antigenic evolution in immunodeficient individuals or in SARS-CoV-2-permissive animal species at human proximity. Understanding these factors will enable us to more reliably evaluate the future population risk of disease in humans and to plan and prepare.
最后这一段是科学界要做的事。略去不译了。
后记：总而言之，认为病毒会向弱化方向进化的基本是一厢情愿，至今还没看到可靠的理论支持。而免疫逃逸的筛选方向本身就会造成免疫屏障的无效化，表现出的重症率即使不因病毒本身毒性提升，也会让人群暴露在危险之下。这样的可能性是机制明确的，不是可能会发生而已，而是没有看到不会发生的机制。不了解这些只能说无知无畏，虽然轻松，但没有什么可以骄傲的。因为它不会因为你不了解而不发生。
当然，同样的道理。最坏的情况也不会因为科学家这样想就会发生。科学界也只能基于一些已知的知识构建模型。事情当然有可能会存在尚未认知的因素，出乎科学家的预料。
但问题是，我们应该赌哪一边呢？
毕竟都收了钱，不丢人。
十四天潜伏期，传播率大的夸张的病毒它有什么理由不点致死率?这就是个概率。
病毒如果传播力不够，那么只有低死亡率的病毒才能繁衍下来，自然选择。
但是新冠传播力太强，死亡率高代表对寄生体更强的营养吸收能力，反而很有可能出现高致病高传播。
按照躺平派的说法，世界医疗最先进的一定是非洲，几十万年坐等病毒减弱的先进经验。
问题你看，有哪个躺平的说自己想去非洲了?点开了主页，一溜烟的发达国家，非洲屁都没有一个。
俗话说得好，别听对方怎么说，看对方到底怎么做。