FlyTitle: The coronavirus pandemic

How an antibody test for the novel coronavirus should—and should not—be used

应当如何恰当地使用针对新型冠状病毒的抗体检测【新冠报道】

经济学人双语版-检测的证词 Testing’s testimony

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 bloodstream 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.

当一种新病毒入侵人体时,免疫系统会马上发动起来。首先赶到现场的是名为免疫球蛋白M(IgM)的一类抗体分子。它们与病毒表面的蛋白质结合,使其失活,并把它标记出来供巨噬细胞破坏。几天后,系统会产生第二种抗体——免疫球蛋白G(IgG)——来继续战斗。IgM昙花一现。它们在血液中留存三到四周后消失。但IgG构成的免疫则要持久得多,可能持续多年乃至终生。

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 insufficient 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.

用于检测专由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发的这两类抗体的测试盒应该很快就会面市。基因检测已经在探测这种导致新冠肺炎(covid-19)的病毒,它直接寻找鼻咽拭子中当前存在的感染迹象。针对抗体的检测还将能识别出过去曾经感染、现在可能已经免疫的人。在短期内这很重要,因为这可让当局确定谁可以重返工作岗位而不会有感染他人的风险。这对于需要照顾重症患者的医生、护士和其他众多医疗从业人员而言尤为宝贵。长期而言它也很有帮助:揭示病毒在人群中传播的程度,由此判断是否可能已经积累出群体免疫。群体免疫指的是人群中可感染的个体不足,令病毒无法轻易找到新的宿主,因此可以安全地放宽社交疏离和居家规定。

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抗体检测已在中国、新加坡和韩国做了有限数量的部署。包括美国和英国在内的几个西方国家政府已经从中国购买了数百万套过剩的抗体检测试剂盒用于本国。世界各地的公司还研发了另外几种抗体检测试剂盒。但是还没有哪一种方法被批准广泛使用,因为尽管这类检测试剂盒比较容易制造,要确保它们给出有用和可靠的结果仍需要大量的工作。

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 Biopanda 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 15 minutes to get a result, and this is displayed in a similar fashion to that used by a typical pregnancy test—the positive identification of an antibody resulting in a coloured line next to its label on the test stick.

每种不同的检测设计都使用自己的化学和工艺配方。但是,从外形上看,很多都和英国的生物熊猫试剂公司(Biopanda Reagents)生产的独立操作塑料棒相似。用户先刺一下指尖,然后将几滴血引入塑料棒一端的开口中。血液在塑料棒内部经过一系列化学过程来识别特定的抗体。大约15分钟后出结果,显示方式与常见的验孕棒类似——如果抗体测定阳性,检测棒的标签旁边会出现一条彩色的线。

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 some time 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.)

引发注意的信号有三种。IgM单阳性表示该人在近日(也许是当前)被感染。IgM和IgG同时阳性,表示使用者在过去一个月中的某个时刻被感染。IgG单阳性意味着感染在一个多月前发生,因此使用者现在应该对感染免疫。(阴性结果可能意味着没被感染,尽管这也可能意味着处于感染太早的阶段而尚未出现抗体,因为IgM通常在感染开始后7到10天才出现。)

Before regulators can approve a test for widespread 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.

监管机构在批准一项检测可被广泛使用前需要验证其有效性。验证过程中可以通过确定两个数字来概括它多有用: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.

检测的灵敏度是指它探测到应该探测的东西的能力——这里就是与SARS-CoV-2相关的IgM和IgG抗体。如果灵敏度是95%,就意味着在100个已知被感染(通过其他方式确定,例如之前的基因检测)的血液样本中,该检测将可靠地把95个样本正确标记为具有相关抗体。其余5个将被识别为不存在抗体——换句话说就是假阴性。

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.

另一个重要的数字是检测的特异性,衡量的是这个检测在仅仅探测应该探测的抗体这一点上的表现。人类冠状病毒一共有七种,理想情况下,一项检测应该只探测因SARS-CoV-2产生的抗体。如果检测的特异性为98%,意味着在100个已知的未感染血液样本中,有98个(被正确地)报告阴性,最后两个(被错误地)报告阳性。这种假阳性的原因可能有很多。常见的一个是交叉反应,也就是检测对错误的抗体做出了反应。

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.

为了确定某项检测的灵敏度和特异性,需要用成百上千个已知状态的样本来验证。由于SARS-CoV-2很新,缺乏便捷的途径来获取相关血液样本,这就需要一些时间。英美两国当局正在评估几项检测,但尚未发布任何验证数据,并且对何时会发布三缄其口。

Sense and specificity

感知与特异

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.

理想的检测应该是100%灵敏和100%特异的。在实际情况下,两者之间总会有取舍。如果让一项检测非常灵敏,哪怕出现一丁点相关抗体也能给出阳性信号,那么特异性就会降低。这是因为这样精细的化学反应很容易被与标靶相似但不相同的抗体触发。反之亦然。

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.

这种取舍并不总是一件坏事,因为可以在不同情况下使用不同类型的检测。例如,如果检测的目的是找到拥有SARS-CoV-2抗体的医护,让他们安全地恢复工作来照顾受感染的患者(因为他们现在已经对感染免疫了),那么检测最重要的一点就是假阳性率要低。换句话说,它需要高度的特异性。

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,如果是收集传播数据,则要灵敏度优先。如果确认了某人已被感染,则可以通过进一步的检测来追踪哪些熟人也被感染,或是曾经被感染而现在免疫。在这种情况下,一些假阳性不会带来灾难。这些假阳性最终也很可能会被发现,因为他们周围的人被感染的概率低于预期。但是,假阴性却意味着丢失信息并导致未能追踪接触者,那可就严重了。

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.

这一类检测可以让医生了解局部聚集性感染的增长情况,从而了解应采取何种措施来打破传染链条(实践中意味着需要隔离谁)。通过对病毒进行基因检测,韩国展开的这种接触者追踪和隔离成效卓著。抗体检测同时捕获过去和当前感染者的数据,可进一步加强这一过程。

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.

儿童是另一个可以利用抗体检测来监测而令整体获益的群体。现在人们已经确定,比起成年人,儿童不大会表现出新冠肺炎症状,并且很少出现重症。但是,目前尚不清楚儿童在多大程度上被“隐性”感染,从而在自己看起来依然健康的情况下传染周围的人。抗体检测将揭示更完整的图景。

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,想要了解自己的免疫状态的公众也会有做抗体检测的需求——哪怕只是为了换得一个安心。这可能会导致冲突。即便在检测设备被获准通用之后,制造商要扩大生产也需要时间,而从事医护和其他一两个重要领域(如教学、治安、将食品杂货运送到商店和市场)的人肯定也会排在检测队伍的最前面。因此,毫不意外,一些不择手段的在线供应商已经开始出售据称供家庭使用的未经验证的测试盒。比如英国的医疗监管机构就不得不关闭了几个欺诈性网站,并警告人们不要使用网上出售的任何家用测试盒。

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 by-product, provide information to individual members of the public. But its primary purpose will be to track how the epidemic is progressing.

即使等到有更多测试盒可用的时候(并恰当地承认不同类型的检测有不同的设计用途),大多数国家在保护好劳动力中的关键成员之后,下一个目标将是全民监控。这附带着给出了一些个体想知道的信息,但主要目的还是追踪流行病在国家内部的进程。

经济学人双语版-检测的证词 Testing’s testimony

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.

这项分析中最重要的元素之一将是确定隐性感染率——以及它对于群体免疫的任何影响。比较来自荷兰和冰岛的最新检测数据,就可以看出当前对于可能有多少隐性感染者的认识存在多大的欠缺。两国都进行了病毒基因检测,但荷兰仅检测那些出现严重症状的人,而冰岛一直在进行广泛的检测,哪怕是没有症状的人。毫不意外而至关重要的是,冰岛的方法找出的年轻感染者远多于荷兰人(见图)。此外,领导冰岛检测项目的卡里·斯特凡松(Kari Stefansson)说,测定为阳性的人中有50%没有症状。

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-throughput 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.

大规模检测会很费劲。即使实际的分析将由集中式高通量实验室中的机器人完成,也需要为数百万人定期采集血液样本。为降低工作量,此类项目可能会被搭载在一个国家的输血服务上,因为捐献的血液本来也要经过严格的病原体筛查。

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 may be given a certificate exempting them from restrictions on working or travelling. If nothing else, that would certainly be an incentive to sign up. ■

德国科学家称计划在本月开始一个规模还算大的监测项目。它将检测定期从10万名参与者那里采集的血液样本。那些被证明已有免疫力的人将获得免除工作或旅行限制的证书。就为了这一点也值得报名了。■