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什么是抗体检测?检测结果有什么意义?

什么是抗体检测?检测结果有什么意义?

Sy Mukherjee 2020年05月16日
美国FDA紧急授权了12个新冠病毒抗体血液检测项目,这种检测对识别高危人群特别有用。

抗体是一种奇特的生物怪兽。这些Y形蛋白质的存在表明,人体免疫系统对生物入侵者作出了反应。它们能够粘附在病毒或其他敌人的特定部位,集结力量将病原体杀死,使其失去效力。在实验室,研究人员可以通过诱导免疫反应来制造抗体,从而创造出药物来对抗从癌症到新冠病毒本身在内的一切疾病。至关重要的是,在新冠病毒肆虐期间,意识到抗体的存在对于遏制疫情、探索经济和社会的重启之策意义重大。

新冠疫情危机引发了一系列问题,触及到科学、流行病学和公共卫生机制的痛处。我们对病毒的传播了解多少?哪些治疗方法可能有效,哪些无效?回归“正常”的最佳策略是什么?

接受《财富》采访的政府高官、制药业资深人士和学术专家都表示,抗体检测将是回答这些问题的关键工具。但是,就像所有与这种阴险病毒相关的事情一样,这件事很复杂。我们需要时间分析信息,制定出适当的监管方针,以确定哪种检测最有效,并搞清楚这些检测究竟揭示了新冠病毒和相关免疫力的哪些性质。

抗体检测亟需审查

任何诊断方式都面临一个很简单的关键问题:这东西真的管用吗?但令人沮丧的是,回答这个问题的难度或许远超你的想象。在一场流行病疫情期间,监管机构必须设法平衡在患者身上快速试验的需求,同时还要评估其疗效。

到目前为止,美国食品与药品管理局(FDA)已经紧急授权了12个新冠病毒抗体血液检测项目。最初采取的全权委托方式招致了医学界的批评。一些人警告说,这可能会引来一些狗皮膏药叫卖者,给公众留下不准确的信息。

就像西部淘金潮再现一样,70多家公司蜂拥而至,争相开发实验性的新冠病毒抗体检测。相较于其他类型的冠状病毒诊断方案,这种测试往往更容易进行。两位FDA高级官员解释说,对紧急授权的审查级别低于根据监管准则授予的“完全批准”或许可。

其他种类的冠状病毒检测,包括所谓的聚合酶链反应(PCR)技术,通常需要鼻腔或咽喉拭子(或两者都需要),而且需要花费更长的时间。它们可能需要在专门的实验室,非常特殊的设备上进行。这些测试可以告诉医疗专家某人是否有“急性感染”,即病毒是否在他们的系统内活跃传播。

但抗体检测是一种血清学测试,可以通过简单的抽血来帮助确定某人是否曾经感染过新冠病毒。从理论上讲,康复患者可以安全地返回工作岗位或者进入公共场合,而不会出现把病毒传播给易感人群的风险。

麻烦在于,我们仍然不确定冠状病毒抗体的存在意味着什么。这是否表示就像大多数感染SARS(这是一种不同类型的冠状病毒)的患者那样,拥有长达两年的免疫期?或者是更短的免疫期?有报道称,一些患者在首次感染后再次检测呈阳性,但尚不清楚这是否是最初的假阳性结果所致。具体来说,哪些公司的检测将提供最准确的信息?

“其中一大挑战是,这是一种新病毒。”佛罗里达大学生物统计学助理教授、流行病学专家纳塔利·迪恩说,“或许会有某种程度的免疫力,但我们不知道这种免疫力能持续多久。我们必须对患者的抗体进行长期追踪。”

FDA高级官员指出,就抗体检测而言,这是一个鸡生蛋还是蛋生鸡的难题。该机构在3月确定的初始工作重点是,提供广泛的抗体检测渠道。上述官员强调称,非紧急情况下的诊断需要提交更多的数据。

本月早些时候,FDA更新了3月首次就抗体检测发布的指导意见,以打击做出误导性声明的公司,并明确其质量控制责任。

FDA 在5月发布的公开声明写道:“3月16日发布政策时,我司认为,相较于旨在检测新冠病毒是否存在的分子检测,对抗体检测采用更高灵活性是合适的,因为它并不是用来诊断活跃的新冠病毒感染的。”该声明补充说,超过200种抗体检测正在走紧急使用前授权或授权流程。他们还表示,FDA正在与美国国立卫生研究院及美国疾病控制中心合作,以确定某些检测的有效性。

在4月投放市场的许多抗体检测,甚至还没有获得FDA的批准,更不用说对其准确性进行更广泛的评估了。

最有希望的抗体检测是什么?

作为此次美国疫情的震中城市,纽约市已经启动了一项免费且广泛的抗体检测计划,最多可能惠及14万居民。问题在于,即使冠状病毒抗体最终能在一段时间内带来免疫力,但检测无法成为让人们重返工作岗位的可靠工具,除非采用一个基准来衡量这种测试的有效性。

在确定抗体检测的准确性方面,有两个关键指标:其一是所谓的“敏感性”,它显示一项测试能够多么准确地识别那些确实有抗体,并由此判断感染过新冠病毒的人(也被称为真实的阳性率)。其二是“特异性”,它提供的是数据的另一面,即没有抗体的人。

罗氏诊断公司的首席医疗官艾伦·赖特说:“敏感性旨在识别那些感染过病毒的人,而特异性是发现过去或最近没有感染的人。”该公司声称拥有最精确的新冠病毒抗体检测之一,已获得紧急使用授权。

罗氏公司表示,其诊断方法拥有高达100%的敏感性和超过99.8%的特异性。其竞争对手、获得两项紧急授权的雅培实验室也宣称,它的抗体检测拥有类似的准确性。

FDA官员和罗氏公司的赖特都强调了结合使用多种检测手段,以及跨机构共享数据的重要性,因为这有助于真正理解免疫范围和公众的感染率。在过去几个月,加州大学伯克利分校、加州大学旧金山分校和其他学术机构组建的研究团队,一直在竭力验证市场上测试的准确性,其结果明显好坏参半。

“这是一系列测试的一部分。”赖特说,“我们不会孤立地进行诊断。”例如,罗氏等公司可能需要在PCR测试确定感染冠状病毒的几周后,才能对其抗体检测的敏感性和特异性进行评估。

这些测试的准确性还有助于制药商了解研发新冠药物和疫苗的最佳方法。关于免疫力和新冠病毒抗体持久力的长期数据可能预示着,未来的新冠疫苗是一次性的(比如麻疹疫苗)还是季节性的(比如流感疫苗)。但这一过程需要更长时间才能完成。

“诊断方法有两个部分需要获得批准。”赖特说,“一个是分析证据,或者只是一般性的数据收集。另一个是临床证据,它可以加速药物开发过程,并告诉我们更多关于免疫和病毒对健康系统长期影响的信息。”

这些是了解一个新病原体的基本方面。“抗体检测让我们对疾病的范围有了更全面的了解。”生物统计学家迪恩表示,“这种检测对识别高危人群特别有用,有助于我们观察风险最高的职业,比如人们近距离相处的工厂。但你必须从一堆来源中把这些东西拼凑起来。”(188金宝搏 下载)

译者:任文科

抗体是一种奇特的生物怪兽。这些Y形蛋白质的存在表明,人体免疫系统对生物入侵者作出了反应。它们能够粘附在病毒或其他敌人的特定部位,集结力量将病原体杀死,使其失去效力。在实验室,研究人员可以通过诱导免疫反应来制造抗体,从而创造出药物来对抗从癌症到新冠病毒本身在内的一切疾病。至关重要的是,在新冠病毒肆虐期间,意识到抗体的存在对于遏制疫情、探索经济和社会的重启之策意义重大。

新冠疫情危机引发了一系列问题,触及到科学、流行病学和公共卫生机制的痛处。我们对病毒的传播了解多少?哪些治疗方法可能有效,哪些无效?回归“正常”的最佳策略是什么?

接受《财富》采访的政府高官、制药业资深人士和学术专家都表示,抗体检测将是回答这些问题的关键工具。但是,就像所有与这种阴险病毒相关的事情一样,这件事很复杂。我们需要时间分析信息,制定出适当的监管方针,以确定哪种检测最有效,并搞清楚这些检测究竟揭示了新冠病毒和相关免疫力的哪些性质。

抗体检测亟需审查

任何诊断方式都面临一个很简单的关键问题:这东西真的管用吗?但令人沮丧的是,回答这个问题的难度或许远超你的想象。在一场流行病疫情期间,监管机构必须设法平衡在患者身上快速试验的需求,同时还要评估其疗效。

到目前为止,美国食品与药品管理局(FDA)已经紧急授权了12个新冠病毒抗体血液检测项目。最初采取的全权委托方式招致了医学界的批评。一些人警告说,这可能会引来一些狗皮膏药叫卖者,给公众留下不准确的信息。

就像西部淘金潮再现一样,70多家公司蜂拥而至,争相开发实验性的新冠病毒抗体检测。相较于其他类型的冠状病毒诊断方案,这种测试往往更容易进行。两位FDA高级官员解释说,对紧急授权的审查级别低于根据监管准则授予的“完全批准”或许可。

其他种类的冠状病毒检测,包括所谓的聚合酶链反应(PCR)技术,通常需要鼻腔或咽喉拭子(或两者都需要),而且需要花费更长的时间。它们可能需要在专门的实验室,非常特殊的设备上进行。这些测试可以告诉医疗专家某人是否有“急性感染”,即病毒是否在他们的系统内活跃传播。

但抗体检测是一种血清学测试,可以通过简单的抽血来帮助确定某人是否曾经感染过新冠病毒。从理论上讲,康复患者可以安全地返回工作岗位或者进入公共场合,而不会出现把病毒传播给易感人群的风险。

麻烦在于,我们仍然不确定冠状病毒抗体的存在意味着什么。这是否表示就像大多数感染SARS(这是一种不同类型的冠状病毒)的患者那样,拥有长达两年的免疫期?或者是更短的免疫期?有报道称,一些患者在首次感染后再次检测呈阳性,但尚不清楚这是否是最初的假阳性结果所致。具体来说,哪些公司的检测将提供最准确的信息?

“其中一大挑战是,这是一种新病毒。”佛罗里达大学生物统计学助理教授、流行病学专家纳塔利·迪恩说,“或许会有某种程度的免疫力,但我们不知道这种免疫力能持续多久。我们必须对患者的抗体进行长期追踪。”

FDA高级官员指出,就抗体检测而言,这是一个鸡生蛋还是蛋生鸡的难题。该机构在3月确定的初始工作重点是,提供广泛的抗体检测渠道。上述官员强调称,非紧急情况下的诊断需要提交更多的数据。

本月早些时候,FDA更新了3月首次就抗体检测发布的指导意见,以打击做出误导性声明的公司,并明确其质量控制责任。

FDA 在5月发布的公开声明写道:“3月16日发布政策时,我司认为,相较于旨在检测新冠病毒是否存在的分子检测,对抗体检测采用更高灵活性是合适的,因为它并不是用来诊断活跃的新冠病毒感染的。”该声明补充说,超过200种抗体检测正在走紧急使用前授权或授权流程。他们还表示,FDA正在与美国国立卫生研究院及美国疾病控制中心合作,以确定某些检测的有效性。

在4月投放市场的许多抗体检测,甚至还没有获得FDA的批准,更不用说对其准确性进行更广泛的评估了。

最有希望的抗体检测是什么?

作为此次美国疫情的震中城市,纽约市已经启动了一项免费且广泛的抗体检测计划,最多可能惠及14万居民。问题在于,即使冠状病毒抗体最终能在一段时间内带来免疫力,但检测无法成为让人们重返工作岗位的可靠工具,除非采用一个基准来衡量这种测试的有效性。

在确定抗体检测的准确性方面,有两个关键指标:其一是所谓的“敏感性”,它显示一项测试能够多么准确地识别那些确实有抗体,并由此判断感染过新冠病毒的人(也被称为真实的阳性率)。其二是“特异性”,它提供的是数据的另一面,即没有抗体的人。

罗氏诊断公司的首席医疗官艾伦·赖特说:“敏感性旨在识别那些感染过病毒的人,而特异性是发现过去或最近没有感染的人。”该公司声称拥有最精确的新冠病毒抗体检测之一,已获得紧急使用授权。

罗氏公司表示,其诊断方法拥有高达100%的敏感性和超过99.8%的特异性。其竞争对手、获得两项紧急授权的雅培实验室也宣称,它的抗体检测拥有类似的准确性。

FDA官员和罗氏公司的赖特都强调了结合使用多种检测手段,以及跨机构共享数据的重要性,因为这有助于真正理解免疫范围和公众的感染率。在过去几个月,加州大学伯克利分校、加州大学旧金山分校和其他学术机构组建的研究团队,一直在竭力验证市场上测试的准确性,其结果明显好坏参半。

“这是一系列测试的一部分。”赖特说,“我们不会孤立地进行诊断。”例如,罗氏等公司可能需要在PCR测试确定感染冠状病毒的几周后,才能对其抗体检测的敏感性和特异性进行评估。

这些测试的准确性还有助于制药商了解研发新冠药物和疫苗的最佳方法。关于免疫力和新冠病毒抗体持久力的长期数据可能预示着,未来的新冠疫苗是一次性的(比如麻疹疫苗)还是季节性的(比如流感疫苗)。但这一过程需要更长时间才能完成。

“诊断方法有两个部分需要获得批准。”赖特说,“一个是分析证据,或者只是一般性的数据收集。另一个是临床证据,它可以加速药物开发过程,并告诉我们更多关于免疫和病毒对健康系统长期影响的信息。”

这些是了解一个新病原体的基本方面。“抗体检测让我们对疾病的范围有了更全面的了解。”生物统计学家迪恩表示,“这种检测对识别高危人群特别有用,有助于我们观察风险最高的职业,比如人们近距离相处的工厂。但你必须从一堆来源中把这些东西拼凑起来。”(188金宝搏 下载)

译者:任文科

Antibodies are curious biological beasts. These Y-shaped proteins—telltale markers that indicate a body's immune system has responded to a biological intruder—can neutralize pathogens by sticking to specific sites on a virus or other adversary and marshaling the forces that can kill them off. They can be manufactured in labs by inducing immune responses in order to create medicines which fight everything from cancer to COVID-19 itself. And, critically, during the coronavirus pandemic, sensing the presence of antibodies will be essential to containing the outbreak and inform how we can reopen the economy and society at large.

The COVID-19 crisis has whipped up a storm of questions which cut to the heart of science, epidemiology, and the broad mechanisms of public health. What do we know about the virus' spread? Which treatments may or may not be effective? What's the best strategy for returning to something approaching "normal"?

Antibody testing will be a key tool for answering those questions, according to senior government officials, pharmaceutical industry veterans, and academic experts who spoke with Fortune. But, as with everything linked to this insidious scourge, it's complicated. It will take time to parse the information and develop the appropriate regulatory guidance we need to figure out which tests work best—and what, exactly, they're telling us about the nature of the coronavirus and immunity to this pathogen.

The 'Wild West' of antibody testing gets a checkup

The key question for any diagnostic is fairly straightforward: Does this thing actually work? But answering it is, frustratingly, trickier than you might think. And in the midst of a pandemic, regulators have to balance the need to rush experimental tests to patients while also gauging their efficacy.

The Food and Drug Administration (FDA) has granted emergency authorization to a dozen COVID-19 antibody blood tests to date. The initial carte blanche approach has elicited criticism from the medical community, with some warning of a "Wild West" scenario that may galvanize snake oil salesmen and leave the public with inaccurate information.

More than 70 companies have flocked to the gold rush that is developing experimental COVID-19 antibody tests, which can be conducted more easily than other types of coronavirus diagnostics. Emergency authorizations come with a lower scrutiny level than full approvals or clearances under regulatory guidelines, two senior FDA officials explained.

Other kinds of coronavirus tests, including so-called polymerase chain reaction (PCR) technology, often require a nasal or throat swab (or both) and take longer to conduct. They may require very specific equipment at specialized labs. These tests can tell medical professionals if someone has an "acute infection"—if the virus is actively circulating in their system.

But antibody tests are serological tests that can be done with a simple blood draw and help determine if someone has had a previous COVID-19 infection they've recovered from. Someone who has recovered could, theoretically, safely return to work or go out in public without risking spreading the coronavirus to more vulnerable people.

The trouble is we're still not sure just what the presence of coronavirus antibodies means. Would they suggest immunity for up to two years, as was the case with most patients who contracted SARS, a different type of coronavirus? Or might it be a shorter immunity period? There have been reports that some patients have re-tested positive after initial infection, though it's unclear whether that's due to an initial false positive result. And which companies' tests, specifically, will provide the most accurate information?

"One of the challenges is that it's a new virus," says Natalie Dean, an assistant professor of biostatistics at the University of Florida and expert in epidemiology. "What's probably going to happen is there's going to be some level of immunity, but we don't know for how long. We're going to have to do followups of patients over time for antibodies."

In the case of antibody tests, this presents a chicken-and-egg dilemma, according to the senior FDA officials. The agency's initial focus in March was on providing widespread access to antibody tests. The officials emphasized that far more data would be required for diagnostics in a non-emergency situation.

The FDA updated its initial March guidance for antibody testing earlier this month in an effort to crack down on companies making misleading claims and to clarify its quality control responsibilities.

"At the time we issued our March 16 policy, a higher level of flexibility was appropriate for antibody tests than for molecular tests that detect the presence of the virus that causes COVID-19, since antibody tests are not meant for use to diagnose active SARS-CoV-2 infection," wrote regulators in a public statement in May, adding that more than 200 antibody tests are going through the pre-emergency authorization or authorization process. They also stated that the FDA is working with the National Institutes of Health (NIH) and Centers for Disease Control (CDC) to determine how effective certain tests are.

Back in April, many of the antibody tests hitting the market hadn't even received FDA authorization, much less a wider accounting of their accuracy.

What are the most promising antibody tests?

New York City, the epicenter of the pandemic, has launched a free and widespread antibody testing effort that could reach up to 140,000 residents. The trouble is that even if coronavirus antibodies ultimately confer immunity for some time, testing can't become a reliable tool for getting people back to work unless there's a baseline of how effective such tests are.

There are two key metrics to determining the accuracy of an antibody test. The first is something called "sensitivity"—this is a measure that tells you how accurate a test is in identifying people who actually have antibodies and thus have been exposed to infection (otherwise known as the the true positive rate). The second is "specificity," which provides the flip side of the data—who doesn't have antibodies.

"Sensitivity is sensing those who have been sick, specificity is spotting the lack of past or recent infection," says Alan Wright, the chief medical officer at Roche Diagnostics, which claims to have one of the most accurate COVID-19 antibody tests cleared for emergency use.

Roche has said that its diagnostic has a staggering 100% sensitivity rate and a more than 99.8% specificity rate. Rival Abbott Laboratories has received two emergency authorizations with similar accuracy claims for its own antibody test.

FDA officials and Roche's Wright underscored the importance of using a combination of tests—and sharing data across agencies—to truly understand the scope of immunity and the infection rate across the public. In the past few months, a team of researchers from UC Berkeley, UCSF, and other academic institutes have been working to validate the accuracy of tests on the market with decidedly mixed results.

"This is part of a suite of tests," says Wright. "We don't approach diagnostics in isolation." For instance, the sensitivity and specificity of an antibody test such as Roche's may have to be done several weeks after an initial coronavirus PCR test which confirms an active infection.

The accuracy of these tests will also help inform drug makers of the best approaches to COVID-19 drug and vaccine development. Longer-term data about immunity and the staying power of COVID-19 antibodies may spell the difference between a one-time vaccine like with measles or a seasonal one such as influenza. But that process will take even longer to play out.

"There are two components to approval for a diagnostic," says Wright. "One is analytical evidence, or just general data-gathering. The other is clinical evidence that can fuel the drug development process and tell us more about immunity and the virus' long-term effects on the health system."

Those are fundamental aspects of understanding a new pathogen. "Antibody tests give us a bigger picture of the range of disease," says Dean, the biostatistician. "They're especially useful for identifying high-risk groups. [They] let us see at the highest-risk occupations such as factories where people are in close quarters. But you have to piece these things together from a bunch of different sources."

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