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在人们开始自由活动之前，冠状病毒抗体检测需要变得更好，我们对免疫的理解也需要提高。
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文 | Neel V.Patel
来源：https://www.technologyreview.com/2020/04/09/998974/immunity-passports-cornavirus-antibody-test-outside/
Why it’s too early to start giving out “immunity passports”
Coronavirus antibody testing needs to get a lot better, and so does our understanding of immunity, before people can start circulating freely.在人们开始自由活动之前，新冠病毒抗体检测需要变得更好，我们对免疫的理解也需要提高。
Imagine, a few weeks or months from now, having a covid-19 test kit sent to your home. It’s small and portable, but pretty easy to figure out. You prick your finger as in a blood sugar test for diabetics, wait maybe 15 minutes, and bam—you now know whether or not you’re immune to coronavirus. 想象一下，从现在开始数周或数月，有一个covid-19检测试剂盒送到您的家中。它既小巧又便于携带，而且很容易搞清楚怎么用。您像在糖尿病患者的血糖测试中那样刺破您的手指，等待大约15分钟，然后砰的一下——您就知道自己是否对冠状病毒有免疫力了。 If you are, you can request government-issued documentation that says so. This is your “immunity passport.” You are now free to leave your home, go back to work, and take part in all facets of normal life—many of which are in the process of being booted back up by “immunes” like yourself. 如果您有免疫力，就可以要求政府签发的证明文件。这是您的“免疫护照”。现在您可以自由离开家，重新上班，并参与各种正常生活，——正常生活的许多方面正在被像你这样的免疫者重启。Pretty enticing, right? Some countries are taking the idea seriously. German researchers want to send out hundreds of thousands of tests to citizens over the next few weeks to see who is immune to covid-19 and who is not, and certify people as being healthy enough to return to society. The UK, which has stockpiled over 17.5 million home antibody testing kits, has raised the prospect of doing something similar, although this has come under major scrutiny from scientists who have raised concerns that the test may not be accurate enough to be useful. As the pressure builds from a public that has been cooped up for weeks, more countries are looking for a way out of strict social distancing measures that doesn’t require waiting 12 to 18 months for a vaccine (if one even comes).很诱人吧？一些国家正在认真考虑这个想法。德国研究人员希望在接下来的几周内向公民发送成千上万的试剂盒，以检测出谁对covid-19有免疫力，谁没有免疫力，并给免疫者发放足够健康可以重返社会的证书。英国已经储备了超过1750万套家用抗体测试试剂盒，也让人们提高了对类似做法的预期，尽管科学家对此大多态度谨慎，因为他们担忧该测试可能达不到实用的准确度。公众被关在家里几周堆积了越来越大的压力，越来越多的国家正在寻找方法摆脱严格的社交隔离措施，而不需要等待12到18个月才会有的疫苗（如果有的话）。 So how does immunity testing work? Very soon after infection by SARS-CoV-2, polymerase chain reaction (PCR) tests can be used to look for evidence of the virus in the respiratory tract. These tests work by greatly amplifying viral genetic material so we can verify what virus it comes from. But weeks or months after the immune system has fought the virus off, it’s better to test for antibodies.那么免疫测试是如何进行的？被SARS-CoV-2感染后不久，聚合酶链式反应（PCR）检测就可以成为寻找呼吸道病毒的手段。这些测试通过放大病毒的遗传物质让我们可以验证它来自什么病毒。但是在免疫系统抵御病毒的几周或几个月之后，更好的办法是检测抗体。About six to 10 days after viral exposure, the body begins to develop antibodies that bind and react specifically to the proteins found on SARS-CoV-2. The first antibody produced is called immunoglobulin m (IgM), which is short-lived and only stays in the bloodstream for a few weeks. The immune system refines the antibodies and just a few days later will start producing immunoglobulins G (IgG) and A (IgA), which are much more specific. IgG stays in the blood and can confer immunity for months, years, or a lifetime, depending on the disease it’s protecting against.
病毒感染后约六至十天，人体开始产生与SARS-CoV-2上发现的蛋白质特异性结合并发生反应的抗体。产生的第一个抗体称为免疫球蛋白m（IgM），寿命短，仅在血液中停留数周。免疫系统会进一步改进抗体，几天后便会开始产生特异性高得多的免疫球蛋白G（IgG）和A（IgA）。IgG会留在血液中，并根据其所针对的疾病而赋予长达数月，数年或一生的免疫力。In someone who has survived infection with covid-19, the blood should, presumably, possess these antibodies, which will then protect against subsequent infection by the SARS-CoV-2 virus. Knowing whether someone is immune (and eligible for potential future certification) hinges on serological testing, drawing blood to look for signs of these antibodies. Get a positive test and, in theory, that person is now safe to walk the street again and get the economy moving. Simple.在感染covid-19后康复的人身上，血液大概会具有这些抗体，从而可以防止之后再次被SARS-CoV-2病毒感染。知道某人是否具有免疫力（并有资格获得未来的潜在认证）取决于血清学测试， 也就是抽血寻找这些抗体的迹象。测试得到阳性结果，然后在理论上，这个人现在就可以安全地再次走上街头，推动经济发展。很简单。Except it’s not. There are some serious problems with trying to use the tests to determine immunity status. For example, we still know very little about what human immunity to the disease looks like, how long it lasts, whether an immune response prevents reinfection, and whether you might still be contagious even after symptoms have dissipated and you’ve developed IgG antibodies. Immune responses vary greatly between patients, and we still don’t know why. Genetics could play a role.但其实并非如此。尝试使用测试确定免疫状态存在一些严重问题。例如，对于人类对这种疾病的免疫力如何，持续多长时间，免疫反应是否能防止再感染，以及即使症状消失并且已经产生IgG抗体，您是否仍具有传染性，我们仍然知之甚少。病人之间的免疫反应差异很大，我们仍然不知道为什么。遗传学可以发挥作用。“We’ve only known about this virus for four months,” says Donald Thea, a professor of global health at Boston University. “There’s a real paucity of data out there.” “我们知道这个病毒只不过四个月而已。”波士顿大学全球卫生学教授唐纳德·西亚（Donald Thea）说：“这里确实缺乏数据。” SARS-CoV-1, the virus that causes SARS and whose genome is about 76% similar to that of SARS-CoV-2, seems to elicit an immunity that lasts up to three years. Other coronaviruses that cause the common cold seem to elicit a far shorter immunity, although the data on that is limited—perhaps, says Thea, because there has been far less urgency to study them in such detail. It’s too early to tell right now where SARS-CoV-2 will fall in that time range. SARS-CoV-1是引起SARS的病毒，其基因组与SARS-CoV-2的基因组相似程度约为76％，似乎可以引发长达三年的免疫力。西亚说，尽管有关数据有限，但其他导致普通感冒的冠状病毒引起的免疫力似乎要短得多，也许是因为如此细致地研究它们的紧迫程度要低得多。现在就预测SARS-CoV-2会落在这个时间区间的哪里还为时过早。 Even without that data, dozens of groups in the US and around the world are developing covid-19 tests for antibodies. Many of these are rapid tests that can be taken at the point of care or even at home, and deliver results in just a matter of minutes. One US company, Scanwell Health, has licensed a covid-19 antibody test from the Chinese company Innovita that can look for SARS-CoV-2 IgM and IgG antibodies through just a finger-prick blood sample and give results in 13 minutes. 即使没有这些数据，美国和世界各地的数十个小组也正在开发针对covid-19抗体的测试。其中许多是可以在护理点甚至在家中进行的快速测试，只需几分钟即可得出结果。美国的一家公司Scanwell Health已获得中国公司英诺特生物技术的covid-19抗体测试许可，该测试可以通过手指刺血样本查找SARS-CoV-2 IgM和IgG抗体，并在13分钟内给出结果。 There are two key criteria we look for when we’re evaluating the accuracy of an antibody test. One is sensitivity, the ability to detect what it’s supposed to detect (in this case antibodies). The other is specificity, the ability to detect the particular antibodies it is looking for. Scanwell’s chief medical officer, Jack Jeng, says clinical trials in China showed that the Innovita test achieved 87.3% sensitivity and 100% specificity (these results are unpublished). That means it will not target the wrong kind of antibodies and won’t deliver any false positives (people incorrectly deemed immune), but it will not be able to tag any antibodies in 12.7% of all the samples it analyzes—those samples would come up as false negatives (people incorrectly deemed not immune).在评估抗体测试的准确性时，我们要寻找两个关键标准。一个是敏感性，即检测到想检测的目标的能力（在这种情况下为抗体）。另一个是特异性，即检测所寻找的特定抗体的能力。Scanwell的首席医学官Jack Jeng表示，在中国的临床试验表明，英诺特检测的灵敏度达到87.3％，特异性达到100％（这些结果尚未公布）。这意味着它将不会针对错误类型的抗体，不会传递任何假阳性（人们错误地认为自己具有免疫力），但是它将无法在其分析的所有样品的12.7％中标记任何抗体——这些样品会成为假阴性（人们错误地认为自己没有免疫力）。By comparison, Cellex, which is the first company to get a rapid covid-19 antibody test approved by the FDA, has a sensitivity of 93.8% and a specificity of 95.6%. Others are also trumpeting their own tests’ vital stats. Jacky Zhang, chairman and CEO of Beroni Group, says his company’s antibody test has a sensitivity of 88.57% and a specificity of 100%, for example. Allan Barbieri of Biomerica says his company’s test is over 90% sensitive. The Mayo Clinic is making available its own covid-19 serological test to look for IgG antibodies, which Elitza Theel, the clinic’s director of clinical microbiology, says has 95% specificity.相比之下，Cellex是第一家获得FDA批准的快速covid-19抗体测试的公司，其敏感性为93.8％，特异性为95.6％。其他各方也在宣扬自己的测试的关键数据。比如，贝罗尼生物科技有限公司董事长兼首席执行官张伯清（Jacky Zhang）说他的公司的抗体检测灵敏度为88.57％，特异性为100％。Biomerica的Allan Barbieri说，他公司的测试灵敏度超过90％。梅奥医学中心正在提供自己的covid-19血清学测试来寻找IgG抗体，该中心临床微生物学总监Elitza Theel表示其具有95％的特异性。The specificity and sensitivity rates work a bit like opposing dials. Increased sensitivity can reduce specificity by a bit, because the test is better able to react with any antibodies in the sample, even ones you aren’t trying to look for. Increasing specificity can lower sensitivity, because the slightest differences in the molecular structure of the antibodies (which is normal) could prevent the test from finding those targets. 特异性和敏感性率有点像相反的表盘。灵敏度提高可能会使特异性降低一点，因为该测试能够更好地与样品中的任何抗体发生反应，即使您不想寻找的抗体也是如此。增加特异性可能会降低灵敏度，因为抗体分子结构的最细微差异（这是正常的）都可能会阻止测试找到那些靶标。“It really depends on what your purpose is,” says Robert Garry, a virologist at Tulane University. Sensitivity and specificity rates of 95% or higher, he says, are considered a high benchmark, but those numbers are difficult to hit; 90% is considered clinically useful, and 80 to 85% is epidemiologically useful. Higher rates are difficult to achieve for home testing kits. 杜兰大学的病毒学家罗伯特·加里（Robert Garry）说：“这真的取决于您的目的。” 他说，敏感性和特异性率达到95％或更高，被认为是一个很高的基准，但是这些数字很难实现。90％被认为在临床上有用，而80％至85％在流行病学上有用。家庭测试套件很难达到更高的比率。But the truth is, a test that is 95% accurate isn’t much use at all. Even the smallest errors can blow up over a large population. Let’s say coronavirus has infected 5% of the population. If you test a million people at random, you ought to find 50,000 positive results and 950,000 negative results. But if the test is 95% sensitive and specific, it will correctly identify only 47,500 positive results and 902,500 negative results. That leaves 50,000 people who have a false result. That’s 2,500 people who are actually positive—immune—but are not getting an immunity passport and must stay home. That’s bad enough. But even worse is that a whopping 47,500 people who are actually negative—not immune—could incorrectly test positive. Half of the 95,000 people who are told they are immune and free to go about their business might never have been infected yet. 但事实是，准确度达95％的测试根本不顶大用。即使是最小的错误，对于巨大的人口基数也会爆炸。假设冠状病毒感染了5％的人口。如果您随机测试100万人，则应该找到50,000个阳性结果和950,000个阴性结果。但是，如果测试具有95％的敏感性和特异性，它将正确地识别出仅47,500个阳性结果和902,500个阴性结果。剩下50,000人的结果是错误的。那意味着有2500人实际上是阳性的，即免疫，但没有获得免疫护照，必须待在家里。这已经够糟糕的了。但更糟糕的是，多达47,500人实际上是阴性（没有免疫力），可能会错误地测试阳性。有95000人被告知有免疫力，可以自由做事，但其中的一半可能从未感染过病毒。Because we don’t know what the real infection rate is—1%, 3%, 5%, etc.—we don’t know how to truly predict what proportion of the immunity passports would be issued incorrectly. The lower the infection rate, the more devastating the effects of the antibody tests’ inaccuracies. The higher the infection rate, the more confident we can be that a positive result is real.因为我们不知道实际的感染率是多少（1％，3％，5％等），所以我们不知道如何真实地预测出被错误颁发的免疫护照所占的比例。感染率越低，抗体测试不准确的影响就越严重。感染率越高，我们就越有信心确定阳性结果是真实的。And people with false positive results would unwittingly be walking hazards who could become infected and spread the virus, whether they developed symptoms or not. A certification system would have to test people repeatedly for several weeks before they could be issued a passport to return to work—and even then, this would only reduce the risk, not eliminate it outright.结果为假阳性的人会不经意间成为安全隐患，无论他们是否出现症状，都可能被感染并传播病毒。认证系统必须对人们进行数周的反复测试，然后才可以给他们发放护照，重返工作岗位。即使那样，也只能降低风险，而不能彻底消除风险。As mentioned, cross-reactivity with other antibodies, especially ones that target other coronaviruses, is another concern. “There are six different coronaviruses known to infect humans,” says Thea. “And it’s entirely possible if you got a garden-variety coronavirus infection in November, and you did not get covid-19, you could still test positive for the SARS-CoV-2 antibodies.” 如上所述，与其他抗体，特别是靶向其他冠状病毒的抗体的交叉反应性是另一个问题。西亚说：“已知有六种不同的冠状病毒可以感染人类。” “而且，如果您在11月感染了常见品种的冠状病毒，并且没有感染covid-19，那完全有可能，您仍然在SARS-CoV-2抗体检测中呈阳性。” Lee Gehrke, a virologist and biotechnology researcher at Harvard and MIT, whose company E25Bio is also developing serological tests for covid-19, raises another issue. “It's not yet immediately clear,” he says, “that the antibodies these tests pick up are neutralizing.” In other words, the antibodies detected in the test may not necessarily act against the virus to stop it and protect the body—they simply react to it, probably to tag the pathogen for destruction by other parts of the immune system. 哈佛大学和麻省理工学院的病毒学家和生物技术研究员李·盖尔克（Lee Gehrke）的公司E25Bio也正在开发针对covid-19的血清学检测，这引发了另一个问题。他说：“目前尚不清楚，这些测试所拾取的抗体是否起效。”换句话说，在测试中检测到的抗体不一定对病毒起作用以阻止它并保护身体，它们只是对它起反应，可能标记病原体以便被免疫系统的其他部分瓦解。 Gehrke says he favors starting with a smaller-scale, in-depth study of serum samples from confirmed patients that defines more closely what the neutralizing antibodies are. This would be an arduous trial, “but I think it would be much more reassuring to have this done in the US before we take serological testing to massive scale,” he says.盖尔克说，他赞成从较小规模的、深入的研究中已证实的患者血清样本开始，以更严密地定义什么是有效抗体。“但是我认为，在我们在美国大规模进行血清学检测之前，先完成这项工作会保险得多。”Alan Wells, the medical director of clinical laboratories at the University of Pittsburgh Medical Center, raises a similar point. He says that some patients who survive infection and are immune may simply not generate the antibodies you’re looking for. Or they may generate them at low levels that do not actually confer immunity, as some Chinese researchers claim to have found. 匹兹堡大学医学中心临床实验室医学主任艾伦·威尔斯（Alan Wells）提出了类似的观点。他说，一些在感染中幸存并具有免疫力的患者可能根本不会产生您要寻找的抗体。也可能像一些中国研究人员声称发现的那样，他们产生的抗体可能太少，实际上不足以赋予免疫力。“I would shudder to use IgM and IgG testing to figure out who’s immune and who’s not,” says Wells. “These tests are not ready for that.” 威尔斯说：“我会因使用IgM和IgG测试来确定谁有和谁没有免疫能力而感到不安。” “这些测试还没有为此做好准备。”Even if the technology is more accurate, it might still simply be too early to start certifying immunity just to open up the economy. Chris Murray from the University of Washington’s Institute for Health Metrics and Evaluation told NPR his group’s models predict that come June, “at least 95% of the US will still be susceptible to the virus,” leaving them vulnerable to infection by the time a possible second wave comes around in the winter. Granting immunity passports to less than 5% of the workforce may not be all that worthwhile. 即使该技术更准确，但开始免疫认证以重启经济可能仍为时过早。华盛顿大学健康指标与评估研究所的克里斯·穆雷（Chris Murray）告诉NPR，他的小组的模型预测，到6月，“至少仍有95％的美国人对病毒易感”，这使得他们在冬天到极有可能来的第二波传染潮中容易受到感染。向少于5％的劳动力发放豁免护照可能根本不是那么值得。”Theel says that instead of being used to issue individual immunity passports, serology tests could be deployed en masse, over a long period of time, to see if herd immunity has set in—lifting or easing restrictions wholesale after 60 to 70% of a community’s population tests positive for immunity. There are a few case studies that hold promise. San Miguel County in Colorado has partnered with biotech company United Biomedical in an attempt to serologically test everyone in the county. The community is small and isolated, and therefore easier to test comprehensively. Iceland has been doing the same thing across the country. Theel说，与其用血清学测试来发放个人免疫护照，不如用它在很长一段时间内进行大规模检查，以查看群体免疫是否已经建立——也就是说，在一个社区的人口有60-70%免疫测试阳性后整个取消或者放松限制。有一些有希望的案例研究。科罗拉多州的圣米格尔县与生物技术公司联合生物医学公司合作，试图对该县的每个人进行血清学检测。这个社区很小而且很孤立，因此更容易进行全面测试。冰岛在全国各地都在做同样的事情。This would require a massively organized effort to pull off well in highly populated areas, and it’s not clear whether the decentralized American health-care system could do it. But it’s probably worth thinking about if we hope to reopen whole economies, and not just give a few individuals a get-out-of-jail-free card. 这将需要进行大规模的组织努力，才能在人口稠密的地区取得成功，目前尚不清楚分散的美国医疗保健系统能否做到这一点。但是那也许值得考虑，如果我们希望重新开放整个经济体，而不仅仅是给一些人保释卡。 Not everyone is so skeptical about using serological testing on a case-by-case basis. Thea thinks the data right now suggests SARS-CoV-2 should behave like its close cousin SARS-CoV-1, resulting in an immunity that lasts for a maybe a couple of years. “With that in mind, it’s not unreasonable to identify individuals who are immune from reinfection,” he says. “We can have our cake and eat it too. We can begin to repopulate the workforce—most importantly the health-care workers.” For instance, in hard-hit cities like New York that are suffering from a shortage of health-care workers, a serological test could help nurses and doctors figure out who might be immune, and therefore better equipped to work in the ICU or conduct procedures that put them at a high risk of exposure to the virus, until a vaccine comes along. 并非每个人都对基于一案一议的血清学检测如此怀疑。Thea认为，目前的数据表明SARS-CoV-2的行为应与其近亲SARS-CoV-1相似，使得它的免疫力大概可以持续几年。他说：“考虑到这一点，确定对再感染有免疫力的个体并非没有道理。” “我们可以两者兼顾。我们可以开始增加劳动力，——最重要的是医疗人员。” 例如，在像纽约这样遭受重创缺少医护人员的城市，血清学检测可以帮助在护士和医生中找出有免疫力的人，从而更好地在重症监护病房工作或参与病毒高暴露风险的工作流程，直到出现疫苗为止。 And at the very least, serological testing is potentially useful because many covid-19 cases present, at most, only mild symptoms that don’t require any kind of medical intervention. About 18% of infected passengers on the Diamond Princess cruise ship showed no symptoms whatsoever, suggesting there may be a huge number of asymptomatic cases. These people almost certainly aren’t being tested (CDC guidelines for covid-19 testing specifically exclude those without symptoms). But their bodies are still producing antibodies that should be detectable long after the infection is cleared. If they develop immunity to covid-19 that’s provable, then in theory, they could freely leave the house once again. 至少，血清学检测可能是有用的，因为许多covid-19病例最多仅表现出不需要任何医学干预的轻度症状。“ 钻石公主”号游轮上约18％的受感染乘客没有任何症状，这表明可能有大量无症状病例。这些人几乎肯定没有受到测试（针对covid-19测试的CDC指南特别排除了没有症状的人）。但是他们的身体仍在产生抗体，这种抗体应在清除感染后很长时间才能检测到。如果他们对covid-19具有的免疫力是可证明的，那么从理论上讲，他们可以再次自由离开家。 For now, however, there are too many problems and unknowns to use antibody testing to decide who gets an immunity passport and who doesn’t. Countries now considering it might find out they will either have to accept enormous risks or simply sit tight for longer than initially hoped.但是到目前为止，对于使用抗体测试来确定谁可以和谁不可以获得免疫护照，还存在太多的问题和未知数。现在正在考虑这样做的国家，可能会发现他们要么不得不承担巨大的风险，要么静坐等待比最初希望的更长的时间。Correction: The initial version of the story incorrectly stated: “The higher the infection rate, the more devastating the effects of the antibody tests’ inaccuracies.” A higher infection would actually produce more confident antibody test results. We regret the error.更正：文章的最初版本错误地指出：“感染率越高，抗体测试不准确的影响就越严重。” 更高的感染实际上会产生更可信的抗体检测结果。对于错误，我们深表歉意。背景简介：文章2020年4月9日发表于 MIT Technology Review（https://www.technologyreview.com/2020/04/09/998974/immunity-passports-cornavirus-antibody-test-outside），风云之声翻译。责任编辑：杨娜