Testing’s testimony
检测的证词
How an antibody test for the novel coronavirus should—and should not—be used
对冠状病毒,该不该使用抗体检测?
When a new virus invades the human body, the immune system leaps into action. First to the scene are antibody molecules of a type called immunoglobulin m (igm). These bind with proteins on a virus’s surface, disabling it and marking it for destruction by cells called macrophages. A few days later the system produces a second type of antibody, immunoglobulin g (igg), to continue the fight. Igms are short-lived. They stick around in the blood-stream for three or four weeks before disappearing. Iggs, however, are the basis for a much longer-term form of immunity. This can last for many years, or even a lifetime.
一旦有新的病毒侵入人体时,免疫系统就会立即启动。首先出现在战场上的是一种叫做免疫球蛋白m(igm)的抗体分子。它们与病毒表面的蛋白质结合,破坏其结构使病毒失效,并且会留下标记让巨噬细胞精准吞噬病毒。几天后,免疫系统会产生第二种抗体——免疫球蛋白g(igg),继续战斗。Igms存在时间很短暂,它们仅在血液中逗留巡逻三到四周就消失不见。而Iggs是长期免疫的基础,它就会存在在身体里很多年,甚至一生。
Kits that test for these two types of antibodies when they have been raised specifically by sars-cov-2 should soon become available. The virus causing the covid-19 is already being detected with genetic tests, which look directly for current signs of infection in nasal or throat swabs. Tests to detect antibodies will also be able to identify those who have had infections in the past and may now be immune. In the short term, this will be important because it will permit the authorities to identify who may return to their jobs without risk of infecting others. That is particularly valuable in the cases of doctors, nurses and the numerous other health-care workers needed to look after those who are seriously ill. It will also help in the longer run, by revealing how far the virus has spread through a population, and thus whether or not herd immunity is likely to have built up. Herd immunity is the point where in sufficient infectible individuals remain in a population for a virus to be able to find new hosts easily, and it is therefore safe to lift social-distancing and stay-at-home rules.
当这两种抗体由sars-cov-2精确地培养时,检测它们的试剂盒将会很快面世。通过基因测试,已经检测出了covid-19的致病病毒,该测试直接在鼻腔或咽拭子中去寻找当前的感染迹象。通过检测抗体的测试办法可以识别到曾经被感染过,现在可以免疫的人。这在短期内很重要,因为这让决策者能够确定谁可以复工而不会感染他人。这对于需要照顾重症患者的医护人员来说尤为重要。这个检测方法通过揭示病毒在人群中的传播程度,从而来确定群体免疫是否可能已经建立,从长远看来,它也有所帮助。群体免疫是一种在种群中存活下了足够数量的针对此病毒的可免疫个体,以使病毒能够轻松找到新宿主的观点,因此可安全地取消社会隔离。
sars-cov-2 antibody tests have already been deployed in limited numbers in China, Singapore and South Korea. Several Western governments, including those of America and Britain, have been buying up millions of surplus antibody tests from China for use in their own countries. Several other types of these tests have also been developed by companies around the world. None, however, has yet been approved for widespread use—for, though such tests are reasonably easy to manufacture, ensuring that they give useful and reliable results is taking a lot of effort.
sars-cov-2抗体测试,已经在中国、新加坡、韩国进行了小范围的展开。包括美国和英国在内的数个西方国家已经从中国购买了数百万过剩的抗体测试试剂,以用于本国检测。然而,没有一种方法被批准广泛使用,因为尽管试剂制造简单,但要确保它们产生有效可靠的结果仍需要努力。
Each different design of test uses its own recipe of chemicals and processes. Physically, however, many resemble the self-contained plastic sticks employed in the version made by Bio panda Reagents, a British firm. A user first pricks a fingertip. Then he or she introduces a few drops of blood into an opening at one end of the stick. Inside, the blood goes through a series of chemical processes that can identify particular antibodies. It takes around 15minutes to get a result, and this is displayed in a similar fashion to that used by atypical pregnancy test—the positive identification of an antibody resulting in a coloured line next to its label on the test stick.
每种测试试剂的设计中都使用的其特有的化学品和工序过程。但从本质上来说,基本都类似于英国公司Bio panda Reagents生产的独立式塑料棒。用户首先刺一下指尖,然后滴几滴血在塑料棒的一端入口中。血液在内部进行一系列识别特定抗体的化学反应。大约15分钟就能有结果,其结果显示方式与验孕棒类似——测试棒的标签旁出现一条彩色线表示抗体检测阳性。
There are three interesting signals. A solitary positive for igm means the person has had a very recent (potentially current) infection. Positives for both igm and igg mean the user was infected sometime within the past month. A positive for igg alone means that the infection occurred more than a month ago, and the user should now be immune to a repeat of it. (A negative result probably means no infection, though it could also mean that it is too early in the course of an infection for antibodies to have appeared, since the first igms typically turn up only 7-10 days after an infection has begun.)
抗体检测试剂会有三种有趣的信号。仅igm检测阳性表示该人近期感染了一次(可能是当前)。Igm和igg都检测阳性表示该检测者在过去一个月的某个时间感染过。仅igg检测阳性表示该检测者已经在一个月多以前感染过,因此其现在对此病毒免疫。(抗体检测结果为阴性可能意味着没有感染,不过也可能意味着检测者处于抗体还未产生的早期感染阶段,因为感染后7-10天后才开始产生抗体。)
Before regulators can approve a test for wide spread use, they need to validate it. How useful it is can be summarised by two numbers determined during this validation: its sensitivity and its specificity.
抗体检测试剂在获得监管机构批准广泛使用之前需要进行验证其效应。在验证期间,其有效性可通过两个参数来概括:灵敏度和特异性。
A test’s sensitivity refers to how good it is at detecting the thing it is meant to detect—in this case the igm and igg antibodies associated with sars-cov-2. A sensitivity of 95% means that, from 100 blood samples known (by other means, such as previous genetic testing) to be infected, the test will reliably tag 95 correctly as having the pertinent antibodies. The remaining five would be identified as having no antibodies present—in other words they would be false negatives.
试剂的灵敏度是指针对指定物质的检测能力优劣程度,在这个案例中,就是针对与sars-cov-2相关的igm和igg抗体。95%的灵敏度意味着,在100个已知被感染(通过其他方式检测的,例如先前的基因检测)的血液样本中,该检测试剂将正确标记95个具有相关抗体的样本。其余五个将被识别为不存在抗体,换句话说,它们是假阴性。
The other significant number, a test’s specificity, measures how good that test is at detecting only the antibodies it is meant to detect. There are seven human coronaviruses and, ideally, a test would detect only antibodies produced in response to sars-cov-2. A test with 98% specificity means that, of 100 known uninfected blood samples, 98 will come back (correctly) as negative and the final two will come back (falsely) as positive. Such false positives could have many causes. A common one is cross-reaction, in which a test responds to the wrong antibodies.
另一个重要的参数,检测试剂的特异性,它衡量该测试试剂在检测需要被检测的抗体方面的能力。目前在人类中存在7种冠状病毒,理想情况下,一次检测只会检测出由于sars-cov-2而产生的抗体。特异性为98%的测试试剂意味着,在100个已知未感染的血液样本中,有98个被正确地检测为阴性,而其余两个被错误地检测为阳性。这种误报可能有很多原因。常见的原因是测试试剂与其他错误的抗体产生了交叉反应。
To work out a test’s sensitivity and specificity, it needs to be checked against hundreds of samples of known status. Given the novelty of sars-cov-2, and therefore the lack of easy access to relevant blood samples, this takes time. The British and American authorities are assessing several tests, but have released no validation data as yet, and have been tight-lipped about when they will do so.
为了确定检测试剂的灵敏度和特异性,需要检测数百个已知状态的对照组样本。鉴于sars-cov-2的新颖性,因此缺乏获取相关血液样本的便捷途径,所以这需要时间。英美两国正在评估数项测试结果,但是还没有发布任何相关验证数据,并且对何时公布守口如瓶。
Sense and specificity
An ideal test would be 100% sensitive and 100% specific. In reality, there will always be a trade-off between the two. Make a test acutely sensitive, so that it gives a positive signal with even the tiniest amounts of a relevant antibody present, and it will get less specific. This is because such a fine chemical hair-trigger is likely to be set off by antibodies similar to, but not identical with the target. And vice versa.
理想的测试试剂,其灵敏度和特异性应该都为100%,但实际上,在这两者之间总会有偏差,需要权衡。做一个灵敏度相关的极端测试,即使只有微量的相关抗体,试剂也会显示检测阳性,这样一来,这种试剂的特异性就会降低。这是因为试剂中的精细化学物很可能是与某种和目标抗体相似的抗体接触,从而产生反应显示结果的,反之,特异性亦然。
This trade-off is not always a bad thing, for it allows different sorts of test to be used in different circumstances. For example, if the intention of testing is to identify doctors and nurses who have antibodies to sars-cov-2, so that they can safely return to work with infected patients, because they are themselves now immune to infection, then the most important thing is for a test to have a low rate of false positives. In other words, it needs a high specificity.
这种权衡并不总是一件坏事,不同的检测目的要求下,需具体情况具体对待。例如,如果检测的目的是检测医护人员是否具有sars-cov-2抗体,从而确定他们可以安全地返回工作岗位照顾患者,因为有抗体表示他们自身可免疫病毒,这种情况下,较低的误报率是最重要的。换句话说,需要检测试剂有较高的特异性。
By contrast, if the idea is to gather transmission data, sensitivity is the priority. If someone were identified as having had an infection, further tests could trace which of that person’s acquaintances were also infected, or had once been infected and were now immune. In these circumstances, a few false positives would not be a disaster. They would probably show up eventually, because those around the allegedly infected individual would not be infected as often as expected. A false negative, though, would mean lost information and a consequent lack of contact-tracing. That would be significant.
相反的,如果是为了收集传播的数据,则优先考虑灵敏度。如果某人被确诊感染,进一步的测试可追踪此人的密切接触者是否也感染了或是曾经感染过,现在有了免疫能力。在这种情况下,少数误报并不会造成很大影响。他们最终可能会出现症状,因为那些密切接触者并不会像预期的那样被感染。然而,如果是假阴性,那就意味着信息缺失,意味着中断了追踪的联系性。所以,灵敏度在这种情况下意义重大。
Testing of this sort will let doctors understand how a local cluster of infections grows, and therefore what action to take in order to break the chain (meaning, in practice, who needs to be quarantined). This kind of contact-tracing and isolation has been employed to great effect in South Korea through the use of genetic tests for the virus. Antibody tests will enhance the process, by capturing data on those infected in the past as well as the present.
这些检测将利于医生了解局部感染群会如何增长,以及如何采取措施去中断感染链(在实践中即意味着谁需要隔离)。通过基因检测手段,检测追踪密切接触者和及时隔离的方法在韩国取得了很大成效。抗体检测不仅可获得现在的数据,还可获取过去感染者的数据,这将会更有利于控制疫情。
Children are another group who could profitably be monitored using antibody tests. It is now well established that they are less likely than adults to present the symptoms of covid-19, and rarely suffer severe disease. It remains unclear, though, to what degree they are being infected “silently”, and are thus able to pass the infection on to others around them while apparently remaining healthy themselves. Antibody tests will reveal a fuller picture.
儿童是另一个可以通过抗体检测而获益的群体。现在已经可以确定的是,儿童比成年人更不易出现感染covid-19后的症状,而且很少会发展成重症。然而,因为他们表现出“无症状”,所以不清楚他们被感染的程度,因此,他们能够在自己保持健康的情况下传染给身边人。而抗体检测将会显示更加全面的情况。
Antibody tests will no doubt also be in demand from members of the public wanting to know their immune status—for their peace of mind if nothing else. This might be cause for conflict. Even when they are cleared for general use it will take time for manufacturers to ramp up the production of tests, and those working in health care and one or two other important areas, like teaching, policing and delivering groceries to stores and markets, will surely be at the head of the queue to be tested. It is therefore hardly surprising that unvalidated kits, purportedly for domestic use, are already being offered for sale by unscrupulous online suppliers. Britain’s medical regulator, for one, has had to take down several fraudulent websites and is warning people not to use any home testing kits they find being sold online.
毫无疑问,想要了解自身免疫情况的公众也会要求进行抗体检测——只为安心。这可能会引起冲突。尽管他们很清楚,如果大众都需要使用的话,试剂生产商将要加大生产规模,而且,那些在一线或其他重要领域——例如教学,治安,运输业的工作者应该被优先检测。因此,毫无悬念,一些无道德的线上供应商已经在出售据称是民用的无效的检测试剂。英国的医疗监管机构已经取缔了几个欺诈网站,并警告人们不要使用任何网上家用检测试剂。
Even when more kits do become available (and with due acknowledgment to the different putative uses of different sorts of test) the next goal for most countries after protecting crucial members of the workforce will be population-level surveillance. This will, as a byproduct, provide information to individual members of the public. But its primary purpose will be to track how the epidemic is progressing.
即使有更多有效的检测试剂可以使用(并承认不同检测试剂的不一样的假定用途),大部分国家在保护重要的劳动力之后的下一个目标仍将是对人口水平的监测。因此,作为疫情的副产品,这将会向公众的个体提供信息。但是其主要的目的是追踪疫情的发展。
One of the most important elements of this analysis will be determining the rate of silent infection—with all the implications that brings for herd immunity. Comparing recent test data from the Netherlands and Iceland hints at the gap in current knowledge of just how much silent infection there may be. Both countries use genetic testing for the virus, but the Netherlands only tests those with severe symptoms of covid-19, whereas Iceland has been testing widely, even people without symptoms. Unsurprisingly, but crucially, the Icelandic approach has revealed far more infections in younger people than the Dutch one (see chart). Moreover, according to Kari Stefansson, who is leading the Icelandic project, 50% of those who have tested positive reported no symptoms.
这项分析的最重要要素之一是确定隐性感染的比例——即产生群体免疫的重要表现。通过对比荷兰和冰岛最近的检测数据,我们可以发现,关于隐性感染的具体数据用目前的知识还无法确定。两个国家都进行了基因检测的方法,但是荷兰仅检测出现严重的covid-19症状的患者,而冰岛一直在进行地毯式检测,甚至对没有出现症状的人也进行检测。不出所料,但是至关重要的是,对比荷兰,冰岛的这种方法在年轻人中发现了更多的患者(见图表)。此外,根据冰岛项目负责人Kari Stefansson的说法:50%检测呈阳性的人没有出现感染症状。
Silence is not golden
沉默不是金
Mass testing will be laborious. It will mean taking regular blood samples from millions of people, even though the actual analysis will be done by robots in centralised high-through put laboratories. To save effort, such projects might piggyback on a country’s blood-transfusion services, for donated blood is already subject to rigorous screening for pathogens.
大规模的检测意味着将需要定期采集数百万人的血液样本,即使实际的检测分析将由机器人在中央高通量实验室完成,但还是会消耗巨大。为了节省人力,这些项目可能会借助国家输血服务系统,因为捐献的血液已经经过了严格的病原体筛选。
German scientists have announced plans to start, this month, a reasonably large-scale surveillance project. It will monitor blood samples taken regularly from 100,000 participants. Those proving immune maybe given a certificate exempting them from restrictions on working or travelling. If nothing else, that would certainly be an incentive to sign up.
德国科学家已经宣布,在本月将会一项规模巨大的监测项目。它将定期监测10万名参与者的血液样本。那些被证实已经对病毒免疫的人将会得到一个证明,以免除对他们的工作或旅行的限制。如果没有其他原因,这肯定会刺激大众参与其中。