AS EVIDENCE MOUNTS THAT THE"GOLD STANDARD"TEST FOR DETECTING COVID-19 IS UNRELIABLE,WHY ARE HEALTH OFFICIALS AROUND THE WORLD CALLING FOR MORE TESTS?
In the months since the COVID-19 panic began health authorities around the world have told the public to"get tested"to help track the spread of SARS-CoV-2.However,as fear and hysteria subside,the scientific community and public at large are calling into question the efficacy of the test used to determine a patients status.This article is a brief examination of the evidence that the PCR test is unreliable and should not be used as a determinant for the number of COVID-19 cases or as a factor in political decisions.
自从2019冠状病毒疾病恐慌开始以来的几个月里，世界各地的卫生当局已经告诉公众去"接受检测"，以帮助跟踪 SARS-CoV-2的传播。然而，随着恐惧和歇斯底里的消退，科学界和广大公众开始质疑用于确定患者状态的测试的有效性。这篇文章是对 PCR 检测不可靠的证据的一个简要检查，不应该被用来作为2019冠状病毒疾病案件数量的决定因素或作为政治决策的一个因素。
HOUSTON HEALTH AUTHORITY HAS CONCERNS ABOUT PCR TEST
休斯顿卫生局对 PCR 检测表示担忧
On August 31,I attended a press conference in Houston to ask the Mayor and Houston Health Authority about reports regarding problems with the Texas Department of State Health Services'numbers on COVID-19 cases.TLAV has previously reported on these concerns with the COVID-19 case numbers in Texas.I also had a chance to ask Houston Health Authority Dr.David Persse about concerns around the test used to detect COVID-19.
8月31日，我在休斯顿参加了一个新闻发布会，向市长和休斯顿卫生局询问有关德克萨斯州卫生服务部关于2019冠状病毒疾病病例数据问题的报告。之前曾报道过德克萨斯州2019冠状病毒疾病的病例数量。我还有机会向休斯顿卫生局的 David Persse 博士询问关于用于检测2019冠状病毒疾病的测试的问题。
The most common test is a polymerase chain reaction(PCR)lab test.This incredibly sensitive technique was developed by Berkeley scientist Kary Mullis,for which he was awarded the Nobel Prize in 1993.The test is designed to detect the presence of a virus by amplifying the virus'genetic material so it can be detected by scientists.The test is viewed as the gold standard,however,it is not without problems.
最常见的检测方法是聚合酶链式反应基因聚合酶链反应(PCR)实验室检测。这项令人难以置信的敏感技术是由加州大学伯克利分校的科学家 Kary Mullis 开发的，他因此获得了1993年的诺贝尔奖。该测试旨在通过扩增病毒的遗传物质来检测病毒的存在，以便科学家能够检测到病毒。这个测试被视为金本位，然而，它也不是没有问题。
The PCR test uses chemicals to amplify the virus's genetic material and then each sample goes through a number of cycles until a virus is recovered.This"cycle threshold"has become a key component in the debate around the efficacy of the PCR test.
PCR 检测使用化学物质扩增病毒的遗传物质，然后每个样本经过一系列循环，直到病毒被恢复。这个"循环阈值"已经成为围绕 PCR 检测有效性的争论中的一个关键组成部分。
Dr.Persse says that when the labs report numbers of COVID-19 cases to the City of Houston they only offer a binary option of"yes"for positive or"no"for negative."But,in reality,it comes in what is called cycle-thresholds.It's an inverse relationship,so the higher the number the less virus there was in the initial sample,"Persse explained."Some labs will report out to 40 cycle-thresholds,and if they get a positive at 40–which means there is a tiny,tiny,tiny amount of virus there–that gets reported to us as positive and we don't know any different."
Persse 博士说，当实验室向休斯顿市报告2019冠状病毒疾病病例数量时，他们只提供了一个二元选项:阳性的是，阴性的否。"但在现实中，它存在于所谓的周期门槛中。这是一个相反的关系，所以数量越高，在最初的样本中的病毒就越少，"Persse 解释说。"一些实验室将报告到40个周期阈值，如果他们在40周期时得到阳性结果——这意味着有极少、极少、极少量的病毒——我们得到的报告是阳性的，我们不知道有什么不同。"
Persse noted that the key question is,at what value is someone considered still infectious?
"Because if you test me and I have a tiny amount of virus,does that mean I am contagious?that I am still infectious to someone else?If you are shedding a little bit of virus are you just starting?or are you on the downside?,"Dr.Persse asked in the lobby of Houston City Hall.He believes the answer is for the scientific community to set a national standard for cycle-threshold.
Unfortunately,a national standard would not solve the problems expressed by Dr.Persse and others.
不幸的是，国家标准并不能解决 Persse 博士和其他人提出的问题。
UK PARLIAMENT AND SCIENTISTS HAVE CONCERNS ABOUT PCR TEST
英国议会和科学家对 PCR 检测表示担忧
In the first weeks of September a number of important revelations regarding the PCR test have come to light.First,new research from the University of Oxford's Center for Evidence-Based Medicine and the University of the West of England found that the PCR test poses the potential for false positives when testing for COVID-19.Professor Carl Heneghan,one of the authors of the study,Viral cultures for COVID-19 infectivity assessment–a systematic review,said there was a risk that an increase in testing in the UK will lead to an increase in the risk of"sample contamination"and thus an increase in COVID-19 cases.
在九月的头几个星期，一些关于 PCR 检测的重要发现已经浮出水面。首先，来自牛津大学循证医学和西英格兰大学的最新研究发现，PCR 检测在检测2019冠状病毒疾病时存在假阳性的可能。这项研究的作者之一 Carl Heneghan 教授说，2019冠状病毒疾病感染性评估的病毒培养-一种系统综述，在英国增加检测的风险将导致样本污染的风险增加，从而增加2019冠状病毒疾病病例。
The team reviewed evidence from 25 studies where virus specimens had positive PCR tests.The researchers state that the"genetic photocopying"technique scientists use to magnify the sample of genetic material collected is so sensitive it could be picking up fragments of dead virus from previous infections.The researchers reach a similar conclusion as Dr.David Persse,namely that,"A binary Yes/No approach to the interpretation RT-PCR unvalidated against viral culture will result in false positives with segregation of large numbers of people who are no longer infectious and hence not a threat to public health."
研究小组回顾了25项病毒样本 PCR 检测呈阳性的研究证据。研究人员表示，科学家们用来放大采集到的遗传物质样本的"基因复制"技术非常敏感，以至于可以从以前感染的病毒中找到死亡病毒的碎片。研究人员得出了与 David Persse 博士类似的结论，即"对于未经病毒文化验证的 RT-PCR 解释，采用二元肯定/否定的方法，将导致错误的阳性结果，将大量不再具有传染性，因此不会对公共健康构成威胁的人隔离开来。"
Heneghan,who is also the the editor of BMJ Evidence-Based Medicine,told the BBC that the binary approach is a problem and tests should have a cut-off point so small amounts of virus do not lead to a positive result.This is because of the cycle threshold mentioned by Dr.Persse.A person who is shedding an active virus and someone who has leftover infection could both receive the same positive test result.He also stated that the test could be detecting old virus which would explain the rise in cases in the UK.Heneghan also stated that setting a standard for the cycle threshold would eliminate the quarantining and contact tracing of people who are healthy and help the public better understand the true nature of COVID-19.
同时也是英国医学杂志循证医学编辑的 Heneghan 告诉 BBC，二进制方法是一个问题，测试应该有一个截止点，这样少量的病毒不会导致阳性结果。这是因为 Persse 博士提到的循环阈值。一个正在散播活跃病毒的人和一个有遗留感染的人都可能得到相同的阳性检测结果。他还表示，这项测试可能是检测旧病毒，这可以解释英国病例增加的原因。还指出，为自行车起点设定标准将消除健康人士的隔离和接触追踪，并帮助公众更好地了解2019冠状病毒疾病的真正本质。
The UK's leading health agency,Public Health England,released an update on the testing methods used to detect COVID-19 and appeared to agree with Professor Heneghan regarding the concerns on the cycle threshold.On September 9,PHE released an update which concluded,"all laboratories should determine the threshold for a positive result at the limit of detection."
英国主要的卫生机构，英国公共卫生发布了一份关于检测2019冠状病毒疾病的检测方法的更新，并且似乎同意 Heneghan 教授关于周期阈值的担忧。9月9日，英国公共卫生部发布了一份更新报告，其中总结道:"所有实验室都应该确定检测阳性结果的阈值。"
This is not the first time Heneghan's work has directly impacted the UK's COVID-19 policies.In July,UK health secretary Matt Hancock called for an"urgent review" of the daily COVID-19 death numbers produced by Public Health England after it was revealed the stats included people who died from other causes.The Guardian reported:
这已经不是 Heneghan 的工作第一次直接影响到英国的2019冠状病毒疾病政策了。今年7月，英国卫生大臣 Matt Hancock 呼吁对英国公共卫生部每日公布的2019冠状病毒疾病死亡人数进行一次"紧急审查"，此前该统计数据被披露包括死于其他原因的人。卫报报道:
"The oddity was revealed in a paper by Yoon K Loke and Carl Heneghan of the Centre for Evidence-Based Medicine at Oxford University,called"Why no one can ever recover from Covid-19 in England–a statistical anomaly".
牛津大学循证医学研究中心的 Yoon k Loke 和 Carl Heneghan 在一篇论文中揭示了这种奇怪的现象，题为"为什么没有人能从英格兰的2019冠状病毒疾病中恢复过来——统计学上的反常现象"。
Their analysis suggests PHE cross-checks the latest notifications of deaths against a database of positive test results–so that anyone who has ever tested positive is recorded in the COVID-19 death statistics.
A Department of Health and Social Care source said:'You could have been tested positive in February,have no symptoms,then hit by a bus in July and you'd be recorded as a COVID death.'"
Only days after Hancock called for the review of PHE data,the UK government put an immediate halt to its daily update of death numbers from COVID-19.
就在 Hancock 要求对英国公共卫生部的数据进行审查的几天后，英国政府立即停止了每天更新的2019冠状病毒疾病死亡人数。
On September 8,Heneghan tweeted out another study on the limitations of the PCR test.The study,"SARS-CoV-2 Testing:The Limit of Detection Matters",examines the limit of detection(LoD)for RNA.The researchers note similar problems with the PCR test and the cycle threshold,concluding,"the ultimate lesson from these studies bears repetition:LoD matters and directly impacts efforts to identify,control,and contain outbreaks during this pandemic."
9月8日，Heneghan 在推特上发布了另一项关于 PCR 检测局限性的研究。这项名为"SARS-CoV-2检测:检测物质的极限"的研究检查了 RNA 的检测限。研究人员注意到了 PCR 检测和循环阈值方面的类似问题，并得出结论:"这些研究得出的最终结论值得重复:检测限很重要，直接影响了在这次大流行期间识别、控制和遏制疫情的努力。"
Heneghan also recently told the BMJ ,"one issue in trying to interpret numbers of detected cases is that there is no set definition of a case.At the moment it seems that a polymerase chain reaction(PCR)positive result is the only criterion required for a case to be recognised."
Heneghan 最近还告诉 BMJ，"试图解释侦破案件数量的一个问题是，没有一个案件的固定定义。目前看来，一个聚合酶链式反应(PCR)阳性结果似乎是一个案件被识别的唯一标准。"
"In any other disease we would have a clearly defined specification that would usually involve signs,symptoms,and a test result,"Heneghan explained."We are moving into a biotech world where the norms of clinical reasoning are going out of the window.A PCR test does not equal covid-19;it should not,but in some definitions it does."
Heneghan 解释说:"在任何其他疾病中，我们都会有一个明确的规范，通常包括症状、体征和检测结果。"。"我们正在进入一个生物技术的世界，临床推理的规范正在消失。一次 PCR 检测并不等同于2019冠状病毒疾病，它不应该，但在某些定义中确实如此
Heneghan says he is concerned that as soon as there is the appearance of an outbreak there is panic and over-reacting."This is a huge problem because politicians are operating in a non-evidence-based way when it comes to non-drug interventions,"he stated.
THE EVIDENCE FOR FALSE POSITIVES IS OVERWHELMING
A recent report from NPR outlines the dangers of false positives with the PCR tests.Andrew Cohen,director of the Center for Research on Aquatic Bioinvasions,was hired by the state of California to study an invasion of non-native mussels.The researchers took water samples and used a PCR test to search for genetic material from the mussels.After the tests came back overwhelmingly positive,Cohen grew suspicious.
美国国家公共电台最近的一份报告概述了 PCR 试验假阳性的危险性。安德鲁·科恩，水生生物入侵研究中心主任，受雇于加利福尼亚州，研究非本地贻贝的入侵。研究人员提取了水样，并用 PCR 检测从贻贝中寻找遗传物质。测试结果完全呈阳性后，科恩开始怀疑。
"I began to realize that many of these—if not all of these—were false positives,especially when they started being reported in waters that had chemistry that would not allow the mussels to reproduce and establish themselves,"he told NPR.NPR notes that,depending on the lab,there was a 2 to 8 percent false positive rate.
Once COVID-19 was declared a pandemic,Cohen said he began asking if the reports of people with absolutely no symptoms and positive PCR test results could be false positives."I began wondering whether these asymptomatic carriers weren't in large part or in whole part the human counterparts of those false-positive results of quagga and zebra mussels in all those water bodies across the West,"he said.
一旦2019冠状病毒疾病被宣布为大流行，Cohen 说他开始询问那些完全没有症状和 PCR 检测结果阳性的人的报告是否会是假阳性。他说:"我开始怀疑，这些无症状携带者是否在很大程度上或全部程度上不是西方所有水体中斑马和斑马贻贝假阳性结果的人类对应者。"。
Cohen emphasized the importance of researchers taking potential false positive PCR results seriously."As near as we can tell,the medical establishment and public health authorities and researchers…appear to be assuming that the false-positive rate in in the PCR based test is zero,or at least so low that we can ignore it."
科恩强调了研究人员认真对待可能出现的假阳性 PCR 结果的重要性。"据我们所知，医疗机构、公共卫生当局和研究人员......似乎认为基于 PCR 的检测中的假阳性率为零，或者至少低到我们可以忽略它。"
Cohen is correct that the scientific authorities need to take false positives seriously,especially when a person can be sent to isolate or quarantine for weeks due to a positive test result.Even the U.S.FDA's own fact sheet on testing acknowledges the dangers posed by false positives:
"The CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel has been designed to minimize the likelihood of false positive test results.However,in the event of a false positive result,risks to patients could include the following:a recommendation for isolation of the patient,monitoring of household or other close contacts for symptoms,patient isolation that might limit contact with family or friends and may increase contact with other potentially COVID-19 patients,limits in the ability to work,the delayed diagnosis and treatment for the true infection causing the symptoms,unnecessary prescription of a treatment or therapy,or other unintended adverse effects."
美国疾病控制与预防中心2019-nCoV 实时 RT-PCR 诊断小组的设计是为了尽量减少假阳性检测结果的可能性。然而，如果出现假阳性结果，病人面临的风险可能包括:建议隔离病人，监测家庭或其他密切接触者的症状，病人隔离可能会限制与家人或朋友的接触，并可能增加与其他潜在2019冠状病毒疾病患者的接触，限制工作能力，延迟诊断和治疗导致症状的真实感染，不必要的处方治疗或治疗，或其他意外的不良反应
A CDC fact sheet also acknowledges the possibility of false positives with the PCR test.
疾病预防控制中心的一份资料也承认 PCR 检测存在假阳性的可能性。
Professor Heneghan believes the confusion around COVID-19 has come as a result of a shift away from"evidence-based medicine."In a recent opinion piece published at The Spectator,Heneghan and Tom Jefferson,a senior associate tutor and honorary research fellow at the Centre for Evidence-Based Medicine,University of Oxford,wrote that patients have become a"prisoner of a system labelling him or her as'positive'when we are not sure what that label means."The two scientists offer this conclusion and warning:
教授认为，人们对2019冠状病毒疾病的困惑是因为人们已经远离了循证医学在最近发表在《观察家》杂志上的一篇评论文章中，Heneghan 和牛津大学循证医学研究中心的高级助理导师和荣誉研究员 Tom Jefferson 写道，患者已经成为了"一个系统的囚徒，当我们不确定这个标签意味着什么时，他或她就会被贴上'积极'的标签。"这两位科学家提出了以下结论和警告:
Governments are producing a series of contradictory and confusing policies which have a brief shelf life as the next crisis emerges.It is increasingly clear the evidence is often ignored.Keeping up to date is a full time occupation,and the advances of the last 30 years have at best been put on hold.
The duties of a good doctor include working in partnership with patients to inform them about what they want or need in a way they can understand,and respecting their rights to reach decisions with you about their treatment and care.Questions need to be asked as to how this will occur if you don't see your doctor,particularly if all you have to do is queue in at a drive in to get your answer.
And ultimately what is a'good test'?We think it's the test which helps your doctor narrow the uncertainty around the origins and management of your problem.