外刊翻譯｜Testing’s testimony檢測的證詞

Testing’s testimony

檢測的證詞

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

對冠狀病毒，該不該使用抗體檢測？

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體時，免疫系統就會立即啟動。首先出現在戰場上的是一種叫做免疫球蛋白m（igm）的抗體分子。它們與病毒表面的蛋白質結合，破壞其結構使病毒失效，並且會留下標記讓巨噬細胞精準吞噬病毒。幾天後，免疫系統會產生第二種抗體——免疫球蛋白g（igg），繼續戰鬥。Igms存在時間很短暫，它們僅在血液中逗留巡邏三到四周就消失不見。而Iggs是長期免疫的基礎，它就會存在在身體裡很多年，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.

當這兩種抗體由sars-cov-2精確地培養時，檢測它們的試劑盒將會很快面世。通過基因測試，已經檢測出了covid-19的致病病毒，該測試直接在鼻腔或咽拭子中去尋找當前的感染跡象。通過檢測抗體的測試辦法可以識別到曾經被感染過，現在可以免疫的人。這在短期內很重要，因為這讓決策者能夠確定誰可以復工而不會感染他人。這對於需要照顧重症患者的醫護人員來說尤為重要。這個檢測方法通過揭示病毒在人群中的傳播程度，從而來確定群體免疫是否可能已經建立，從長遠看來，它也有所幫助。群體免疫是一種在種群中存活下了足夠數量的針對此病毒的可免疫個體，以使病毒能夠輕鬆找到新宿主的觀點，因此可安全地取消社會隔離。

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抗體測試，已經在中國、新加坡、韓國進行了小範圍的展開。包括美國和英國在內的數個西方國家已經從中國購買了數百萬過剩的抗體測試試劑，以用於本國檢測。然而，沒有一種方法被批准廣泛使用，因為儘管試劑製造簡單，但要確保它們產生有效可靠的結果仍需要努力。

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.

每種測試試劑的設計中都使用的其特有的化學品和工序過程。但從本質上來說，基本都類似於英國公司Bio panda Reagents生產的獨立式塑料棒。用戶首先刺一下指尖，然後滴幾滴血在塑料棒的一端入口中。血液在內部進行一系列識別特定抗體的化學反應。大約15分鐘就能有結果，其結果顯示方式與驗孕棒類似——測試棒的標籤旁出現一條彩色線表示抗體檢測陽性。

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.)

抗體檢測試劑會有三種有趣的信號。僅igm檢測陽性表示該人近期感染了一次（可能是當前）。Igm和igg都檢測陽性表示該檢測者在過去一個月的某個時間感染過。僅igg檢測陽性表示該檢測者已經在一個月多以前感染過，因此其現在對此病毒免疫。（抗體檢測結果為陰性可能意味著沒有感染，不過也可能意味著檢測者處於抗體還未產生的早期感染階段，因為感染後7-10天後才開始產生抗體。）

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.

抗體檢測試劑在獲得監管機構批准廣泛使用之前需要進行驗證其效應。在驗證期間，其有效性可通過兩個參數來概括：靈敏度和特異性。

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.

試劑的靈敏度是指針對指定物質的檢測能力優劣程度，在這個案例中，就是針對與sars-cov-2相關的igm和igg抗體。95%的靈敏度意味著，在100個已知被感染（通過其他方式檢測的，例如先前的基因檢測）的血液樣本中，該檢測試劑將正確標記95個具有相關抗體的樣本。其餘五個將被識別為不存在抗體，換句話說，它們是假陰性。

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.

另一個重要的參數，檢測試劑的特異性，它衡量該測試試劑在檢測需要被檢測的抗體方面的能力。目前在人類中存在7種冠狀病毒，理想情況下，一次檢測只會檢測出由於sars-cov-2而產生的抗體。特異性為98%的測試試劑意味著，在100個已知未感染的血液樣本中，有98個被正確地檢測為陰性，而其餘兩個被錯誤地檢測為陽性。這種誤報可能有很多原因。常見的原因是測試試劑與其他錯誤的抗體產生了交叉反應。

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.

為了確定檢測試劑的靈敏度和特異性，需要檢測數百個已知狀態的對照組樣本。鑑於sars-cov-2的新穎性，因此缺乏獲取相關血液樣本的便捷途徑，所以這需要時間。英美兩國正在評估數項測試結果，但是還沒有發布任何相關驗證數據，並且對何時公布守口如瓶。

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.

理想的測試試劑，其靈敏度和特異性應該都為100%，但實際上，在這兩者之間總會有偏差，需要權衡。做一個靈敏度相關的極端測試，即使只有微量的相關抗體，試劑也會顯示檢測陽性，這樣一來，這種試劑的特異性就會降低。這是因為試劑中的精細化學物很可能是與某種和目標抗體相似的抗體接觸，從而產生反應顯示結果的，反之，特異性亦然。

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.

這種權衡並不總是一件壞事，不同的檢測目的要求下，需具體情況具體對待。例如，如果檢測的目的是檢測醫護人員是否具有sars-cov-2抗體，從而確定他們可以安全地返回工作崗位照顧患者，因為有抗體表示他們自身可免疫病毒，這種情況下，較低的誤報率是最重要的。換句話說，需要檢測試劑有較高的特異性。

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，如果是為了收集傳播的數據，則優先考慮靈敏度。如果某人被確診感染，進一步的測試可追蹤此人的密切接觸者是否也感染了或是曾經感染過，現在有了免疫能力。在這種情況下，少數誤報並不會造成很大影響。他們最終可能會出現症狀，因為那些密切接觸者並不會像預期的那樣被感染。然而，如果是假陰性，那就意味著信息缺失，意味著中斷了追蹤的聯繫性。所以，靈敏度在這種情況下意義重大。

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.

這些檢測將利於醫生了解局部感染群會如何增長，以及如何採取措施去中斷感染鏈（在實踐中即意味著誰需要隔離）。通過基因檢測手段，檢測追蹤密切接觸者和及時隔離的方法在韓國取得了很大成效。抗體檢測不僅可獲得現在的數據，還可獲取過去感染者的數據，這將會更有利於控制疫情。

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.

兒童是另一個可以通過抗體檢測而獲益的群體。現在已經可以確定的是，兒童比成年人更不易出現感染covid-19後的症狀，而且很少會發展成重症。然而，因為他們表現出「無症狀」，所以不清楚他們被感染的程度，因此，他們能夠在自己保持健康的情況下傳染給身邊人。而抗體檢測將會顯示更加全面的情況。

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.

毫無疑問，想要了解自身免疫情況的公眾也會要求進行抗體檢測——只為安心。這可能會引起衝突。儘管他們很清楚，如果大眾都需要使用的話，試劑生產商將要加大生產規模，而且，那些在一線或其他重要領域——例如教學，治安，運輸業的工作者應該被優先檢測。因此，毫無懸念，一些無道德的線上供應商已經在出售據稱是民用的無效的檢測試劑。英國的醫療監管機構已經取締了幾個欺詐網站，並警告人們不要使用任何網上家用檢測試劑。

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.

即使有更多有效的檢測試劑可以使用（並承認不同檢測試劑的不一樣的假定用途），大部分國家在保護重要的勞動力之後的下一個目標仍將是對人口水平的監測。因此，作為疫情的副產品，這將會向公眾的個體提供信息。但是其主要的目的是追蹤疫情的發展。

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.

這項分析的最重要要素之一是確定隱性感染的比例——即產生群體免疫的重要表現。通過對比荷蘭和冰島最近的檢測數據，我們可以發現，關於隱性感染的具體數據用目前的知識還無法確定。兩個國家都進行了基因檢測的方法，但是荷蘭僅檢測出現嚴重的covid-19症狀的患者，而冰島一直在進行地毯式檢測，甚至對沒有出現症狀的人也進行檢測。不出所料，但是至關重要的是，對比荷蘭，冰島的這種方法在年輕人中發現了更多的患者（見圖表）。此外，根據冰島項目負責人Kari Stefansson的說法：50%檢測呈陽性的人沒有出現感染症狀。

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.

大規模的檢測意味著將需要定期採集數百萬人的血液樣本，即使實際的檢測分析將由機器人在中央高通量實驗室完成，但還是會消耗巨大。為了節省人力，這些項目可能會藉助國家輸血服務系統，因為捐獻的血液已經經過了嚴格的病原體篩選。

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.

德國科學家已經宣布，在本月將會一項規模巨大的監測項目。它將定期監測10萬名參與者的血液樣本。那些被證實已經對病毒免疫的人將會得到一個證明，以免除對他們的工作或旅行的限制。如果沒有其他原因，這肯定會刺激大眾參與其中。

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