2020年9月21日
摘要
隨著越來越多的證據表明，用於檢測2019冠狀病毒疾病的”黃金標準”測試是不可靠的，為什麼世界各地的衛生官員都在呼籲進行更多的測試？
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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?
隨著越來越多的證據表明，用於檢測2019冠狀病毒疾病的"黃金標準"測試是不可靠的，為什麼世界各地的衛生官員都在呼籲進行更多的測試？
相關：
坦桑尼亞總統質疑冠狀病毒檢測，暫停實驗室主任職務
醫學第一!木瓜植物對新型冠狀病毒肺炎病毒呈陽性反應
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.
自從2019冠狀病毒疾病恐慌開始以來的幾個月裡，世界各地的衛生當局已經告訴公眾去"接受檢測"，以幫助跟踪 SARS-CoV-2的傳播。然而，隨著恐懼和歇斯底里的消退，科學界和廣大公眾開始質疑用於確定患者狀態的測試的有效性。這篇文章是對 PCR 檢測不可靠的證據的一個簡要檢查，不應該被用來作為2019冠狀病毒疾病案件數量的決定因素或作為政治決策的一個因素。
HOUSTON HEALTH AUTHORITY HAS CONCERNS ABOUT PCR TEST
休斯頓衛生局對 PCR 檢測表示擔憂
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，我在休斯頓參加了一個新聞發布會，向市長和休斯頓衛生局詢問有關德克薩斯州衛生服務部關於2019冠狀病毒疾病病例數據問題的報告。之前曾報導過德克薩斯州2019冠狀病毒疾病的病例數量。我還有機會向休斯頓衛生局的 David Persse 博士詢問關於用於檢測2019冠狀病毒疾病的測試的問題。
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.
最常見的檢測方法是聚合酶鍊式反應基因聚合酶鏈反應(PCR)實驗室檢測。這項令人難以置信的敏感技術是由加州大學伯克利分校的科學家 Kary Mullis 開發的，他因此獲得了1993年的諾貝爾獎。該測試旨在通過擴增病毒的遺傳物質來檢測病毒的存在，以便科學家能夠檢測到病毒。這個測試被視為金本位，然而，它也不是沒有問題。
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 檢測使用化學物質擴增病毒的遺傳物質，然後每個樣本經過一系列循環，直到病毒被恢復。這個"循環閾值"已經成為圍繞 PCR 檢測有效性的爭論中的一個關鍵組成部分。
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 博士說，當實驗室向休斯頓市報告2019冠狀病毒疾病病例數量時，他們只提供了一個二元選項:陽性的是，陰性的否。 "但在現實中，它存在於所謂的周期門檻中。這是一個相反的關係，所以數量越高，在最初的樣本中的病毒就越少，"Persse 解釋說。 "一些實驗室將報告到40個週期閾值，如果他們在40週期時得到陽性結果——這意味著有極少、極少、極少量的病毒——我們得到的報告是陽性的，我們不知道有什麼不同。"
Persse noted that the key question is,at what value is someone considered still infectious?
佩爾斯指出，關鍵的問題是，在什麼價值下，一個人仍然具有傳染性？
"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.
"因為如果你給我做測試，我體內只有少量的病毒，這是否意味著我具有傳染性？我還會傳染給別人嗎？如果你正在散播一點病毒，你是剛剛開始嗎？還是你正處於下風？博士在休斯頓市政廳的大廳裡問道。他認為，科學界應該為循環閾值制定一個國家標準。
Unfortunately,a national standard would not solve the problems expressed by Dr.Persse and others.
不幸的是，國家標準並不能解決 Persse 博士和其他人提出的問題。
UK PARLIAMENT AND SCIENTISTS HAVE CONCERNS ABOUT PCR TEST
英國議會和科學家對 PCR 檢測表示擔憂
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.
在九月的頭幾個星期，一些關於 PCR 檢測的重要發現已經浮出水面。首先，來自牛津大學循證醫學和西英格蘭大學的最新研究發現，PCR 檢測在檢測2019冠狀病毒疾病時存在假陽性的可能。這項研究的作者之一 Carl Heneghan 教授說，
2019冠狀病毒疾病感染性評估的病毒培養-一種系統綜述，在英國增加檢測的風險將導致樣本污染的風險增加，從而增加2019冠狀病毒疾病病例。
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."
研究小組回顧了25項病毒樣本 PCR 檢測呈陽性的研究證據。研究人員表示，科學家們用來放大採集到的遺傳物質樣本的"基因複制"技術非常敏感，以至於可以從以前感染的病毒中找到死亡病毒的碎片。研究人員得出了與David Persse 博士類似的結論，即"對於未經病毒文化驗證的RT-PCR 解釋，採用二元肯定/否定的方法，將導致錯誤的陽性結果，將大量不再具有傳染性，因此不會對公共健康構成威脅的人隔離開來。"
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.
同時也是英國醫學雜誌循證醫學編輯的 Heneghan 告訴 BBC，二進制方法是一個問題，測試應該有一個截止點，這樣少量的病毒不會導致陽性結果。這是因為 Persse 博士提到的循環閾值。一個正在散播活躍病毒的人和一個有遺留感染的人都可能得到相同的陽性檢測結果。他還表示，這項測試可能是檢測舊病毒，這可以解釋英國病例增加的原因。還指出，為自行車起點設定標準將消除健康人士的隔離和接觸追踪，並幫助公眾更好地了解2019冠狀病毒疾病的真正本質。
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."
英國主要的衛生機構，英國公共衛生髮布了一份關於檢測2019冠狀病毒疾病的檢測方法的更新，並且似乎同意 Heneghan 教授關於週期閾值的擔憂。 9月9日，英國公共衛生部發布了一份更新報告，其中總結道:"所有實驗室都應該確定檢測陽性結果的閾值。"
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:
這已經不是 Heneghan 的工作第一次直接影響到英國的2019冠狀病毒疾病政策了。今年7月，英國衛生大臣 Matt Hancock 呼籲對英國公共衛生部每日公佈的2019冠狀病毒疾病死亡人數進行一次"緊急審查"，此前該統計數據被披露包括死於其他原因的人。衛報報導:
"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".
牛津大學循證醫學研究中心的Yoon k Loke 和Carl Heneghan 在一篇論文中揭示了這種奇怪的現象，題為"為什麼沒有人能從英格蘭的2019冠狀病毒疾病中恢復過來——統計學上的反常現象"。
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.
他們的分析表明，英國公共衛生部將最新的死亡通知與陽性檢測結果數據庫進行交叉核對，以便任何被檢測出陽性的人都被記錄在2019冠狀病毒疾病死亡統計數據中。
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.'"
一位衛生和社會關懷部門的消息人士說:"你可能在二月份被檢測出呈陽性，沒有任何症狀，然後在七月份被一輛公共汽車撞倒，那麼你就會被記錄為因感染而死亡。"
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 要求對英國公共衛生部的數據進行審查的幾天后，英國政府立即停止了每天更新的2019冠狀病毒疾病死亡人數。
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 在推特上發布了另一項關於 PCR 檢測局限性的研究。這項名為"SARS-CoV-2檢測:檢測物質的極限"的研究檢查了 RNA 的檢測限。研究人員注意到了PCR 檢測和循環閾值方面的類似問題，並得出結論:"這些研究得出的最終結論值得重複:檢測限很重要，直接影響了在這次大流行期間識別、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 最近還告訴 BMJ，"試圖解釋偵破案件數量的一個問題是，沒有一個案件的固定定義。目前看來，一個聚合酶鍊式反應(PCR)陽性結果似乎是一個案件被識別的唯一標準。"
"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 解釋說:"在任何其他疾病中，我們都會有一個明確的規範，通常包括症狀、體徵和檢測結果。"。 "我們正在進入一個生物技術的世界，臨床推理的規范正在消失。一次 PCR 檢測並不等同於2019冠狀病毒疾病，它不應該，但在某些定義中確實如此
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.
Heneghan 說，他擔心一旦出現疫情爆發的跡象，就會出現恐慌和反應過度。 "這是一個巨大的問題，因為當涉及到非藥物干預時，政治家們正在以一種非基於證據的方式運作，"他說。
THE EVIDENCE FOR FALSE POSITIVES IS OVERWHELMING
假陽性的證據是壓倒性的
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.
美國國家公共電台最近的一份報告概述了 PCR 試驗假陽性的危險性。安德魯·科恩，水生生物入侵研究中心主任，受僱於加利福尼亞州，研究非本地貽貝的入侵。研究人員提取了水樣，並用 PCR 檢測從貽貝中尋找遺傳物質。測試結果完全呈陽性後，科恩開始懷疑。
"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.
他告訴美國國家公共廣播電台:"我開始意識到，其中許多(如果不是全部的話)都是假陽性，特別是當它們開始被報導出生在化學成分不允許貽貝繁殖和生長的水域時。" 。美國國家公共電台指出，根據實驗室的不同，有2%到8%的假陽性率。
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冠狀病毒疾病被宣佈為大流行，Cohen 說他開始詢問那些完全沒有症狀和 PCR 檢測結果陽性的人的報告是否會是假陽性。他說:"我開始懷疑，這些無症狀攜帶者是否在很大程度上或全部程度上不是西方所有水體中斑馬和斑馬貽貝假陽性結果的人類對應者。"。
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."
科恩強調了研究人員認真對待可能出現的假陽性 PCR 結果的重要性。 "據我們所知，醫療機構、公共衛生當局和研究人員......似乎認為基於 PCR 的檢測中的假陽性率為零，或者至少低到我們可以忽略它。"
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 USFDA's own fact sheet on testing acknowledges the dangers posed by false positives :
科恩的觀點是正確的，科學當局需要認真對待假陽性，尤其是當一個人因為陽性檢測結果而被送去隔離或隔離幾週的時候。甚至美國食品藥品監督管理局自己的檢測情況說明書也承認錯誤陽性的危害:
"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."
美國疾病控制與預防中心2019-nCoV 實時 RT-PCR 診斷小組的設計是為了盡量減少假陽性檢測結果的可能性。然而，如果出現假陽性結果，病人面臨的風險可能包括:建議隔離病人，監測家庭或其他密切接觸者的症狀，病人隔離可能會限制與家人或朋友的接觸，並可能增加與其他潛在2019冠狀病毒疾病患者的接觸，限制工作能力，延遲診斷和治療導致症狀的真實感染，不必要的處方治療或治療，或其他意外的不良反應
A CDC fact sheet also acknowledges the possibility of false positives with the PCR test.
疾病預防控制中心的一份資料也承認 PCR 檢測存在假陽性的可能性。
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 :
教授認為，人們對2019冠狀病毒疾病的困惑是因為人們已經遠離了循證醫學在最近發表在《觀察家》雜誌上的一篇評論文章中，Heneghan 和牛津大學循證醫學研究中心的高級助理導師和榮譽研究員Tom Jefferson 寫道，患者已經成為了"一個系統的囚徒，當我們不確定這個標籤意味著什麼時，他或她就會被貼上'積極'的標籤。"這兩位科學家提出了以下結論和警告:
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.
各國政府正在製定一系列相互矛盾、令人困惑的政策，隨著下一次危機的出現，這些政策的有效期很短。越來越清楚的是，證據往往被忽視。保持最新是一項全職工作，過去30年的進步充其量只能暫時擱置。
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.
一個好醫生的職責包括與患者合作，以他們能夠理解的方式告訴他們他們想要或需要什麼，並尊重他們與你就治療和護理達成決定的權利。如果你不去看醫生，這種情況會怎樣發生，特別是如果你只需要排隊等候就可以得到你的答案。
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.
最終什麼是好的測試？我們認為這個測試可以幫助你的醫生縮小圍繞你的問題的起源和管理的不確定性。
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