大规模的新冠肺炎诊断检测是否永久改变了我们的诊断检测方法

新冠肺炎给英国国家医疗服务体系（NHS）带来了难以置信的压力。来自NHS的数据显示，在大流行发生后的一年里（2021年3月），为了获得NHS提供的15个"关键 "诊断之中的一个，24.3%的患者自转诊之日起等待了6周或更长时间。与2020年3月相比，这一数字（2021年3月）增加了14.1%。2021年3月，疫苗接种计划仍处于早期阶段，NHS仍在对抗病毒的前线。在疫苗接种计划之后，感染新冠肺炎病人的预后诊断有所改善，但撰写本报告时（2022年4月）的最新统计数据表明，在恢复"正常"护理方面尚存在挑战。截至2022年1月，30%的患者等待关键诊断检测的时间为6周或更长，这或许反映了NHS工作人员自我隔离的持续代价和不断增加的工作积压。

COVID-19 has put incredible stress on the NHS. Data from NHS England revealed that one year after the onset of the pandemic (March 2021), 24.3% of patients had been waiting for six weeks or more since the date of their referral for one of 15 ‘key’ diagnostic procedures provided by the NHS. Compared to March 2020, this figure represented a 14.1% (March 2021) increase. In March 2021, the vaccine programme was still in its early stages, and the NHS was on the front line fighting the virus. Despite improvements in the prognosis for patients infected with COVID-19 following the vaccination programme, the most recent statistics available at the time of writing (April 2022) suggest challenges in returning to ‘normal’ care remain. As of January 2022, 30% of patients were waiting for six weeks or more for key diagnostic tests, perhaps reflecting the ongoing toll of self-isolating NHS staff and an increasing backlog.

随着英国政府结束了在英格兰面向公众的免费新冠肺炎检测，政府统计数据表明，检测和追踪计划进行了近5亿次新冠肺炎检测，其中超过2100万次检测结果为阳性。对人口的大规模检测是科学界取得的一个令人难以置信的成就。这项庞大的工作不仅在识别感染者以阻止疾病传播方面至关重要，在识别具有威胁性的新变种方面也是如此，例如VOC-20DEC-01（B.1.1.7；英国变种或肯特郡变种）和VOC-21APR-02（B.1.617.2；德尔塔变种）。2021年末出现的奥密克戎变种的高传染性反映在数据里——2021年11月约800万人检测结果为阳性——五个月之后，这一数字增加了一倍还多，达到了上面提到的2100万。

As the UK government brings free, publicly available testing for COVID-19 to an end in England, government statistics indicate that the test and trace programme recorded nearly 500 million COVID-19 tests, over 21 million of whom tested positive. Mass testing of the population was an incredible achievement by our scientific community. This vast undertaking was not only crucial in identifying the infected to prevent the spread of the disease, but in identifying threatening new variants, such as VOC-20DEC-01 (B.1.1.7; ‘UK’ or ‘Kent’ variant) and VOC-21APR-02 (B.1.617.2; ‘Delta Variant’). The infectiousness of the omicron variant of the virus, which emerged in late 2021 is reflected in the data – in November 2021 around 8 million people had tested positive – in the space of 5 months, this figure over doubled to the 21 million referenced above.

尽管大规模检测在减少，但抗原检测和PCR检测可能仍会是我们生活中的重要组成部分，特别是对于那些希望出国旅行的人和那些与临床弱势群体接触的人。侧向流动检测（LFT）在疫苗未获得批准时作为预防新冠病毒的第一道防线在英国各地展开，现已成为主要的家用物品。这些检测背后的核心技术在大流行之前就为科学界所熟悉，但为了满足对快速和具有成本效益的诊断的突然需求，科学界设计出了新的迭代。

Although mass testing is being wound down, antigen tests and PCR tests will likely remain a feature of our lives going forward, particularly for those wishing to travel abroad, and for those in contact with the clinically vulnerable. Lateral flow tests, now staple household items, were rolled out across the UK as first line of defence against SARS-CoV-2, in the absence of an approved vaccine. The core technologies behind these tests were familiar to the scientific community before the pandemic, but new iterations were devised to meet the sudden demand for quick and cost-effective diagnosis.

大流行的早期阶段突出了对重症护理创新的迫切需要，但由于担心NHS会被危重病人淹没，因此突然迫切需要开发快速且可靠的方法来识别新冠肺炎阳性病例。鉴于危机往往与创新的加速相关，欧洲专利局收到的与医疗技术有关的专利申请数量在2020年相对于2019年增加了2.6%，在2021年相对于2020年增加了0.8%，这也许并不奇怪。

Whilst the early stages of the pandemic highlighted the urgent need for innovation in critical care, the fear that the NHS would be overwhelmed by critically ill patients led to the sudden and urgent need to develop quick and reliable means of identifying positive COVID-19 cases. Given times of crisis often correlate with periods of accelerated innovation, it is perhaps unsurprising that the number of patent applications filed at the European Patent Office relating to medical technologies increased by 2.6% in 2020 relative to 2019, and by 0.8% in 2021 relative to 2020.

新冠肺炎DIY家用检检测剂盒的推出可能代表着我们所熟悉的、由医生主导的传统诊断路径产生了深刻的转变。新冠肺炎检测主要不是由医生和护士进行，而是由研究人员、技术人员、志愿者、部队和个人进行。此外，这些检测不是在医院或全科医生诊所进行的，而是在停车场、体育馆、体育场和家中进行的。此外，在收集了病人的样本后，这些检测可以在病人不在场的情况下远程进行，并可迅速得到结果。DNA扩增和免疫学近几十年来的飞跃使我们能够推出大规模检测，并有效地使我们能够实时提供病毒及其变种在世界各地传播的信息。与1918年最后一次"大"流感的大流行相比，当时只有通过严重的症状才能识别流感病毒的存在，显然我们的诊断能力已经有了很大的进步。

The roll out of ‘DIY’ at home testing kits for COVID-19 may represent a profound shift in the traditional doctor-led route to diagnosis, with which we are all familiar. COVID-19 tests were not primarily performed by doctors and nurses, but by researchers, technicians, volunteers, the armed forces and individuals. Additionally, these tests were not performed in hospitals and GP surgeries, but in car parks, sports halls, stadia and homes. Furthermore, following collection of a patient sample, these tests could be performed remotely in the absence of the patient, and results were available rapidly. Leaps in DNA amplification and immunology in recent decades has underpinned our ability to roll out mass testing, and has effectively enabled us to map the spread of the virus and its variants around the world in real time. Contrast this to the last ‘great’ influenza pandemic of 1918, when the presence of the influenza virus was only identifiable by severe illness, and it is clear how far our diagnosis capabilities have come.

广泛检测的成功和熟悉也许会让病人期望，对于其他病原体和疾病，即时诊断也应该同样直接。小量体液样本，几乎不需要任何医学培训就能取得，可以很容易地用于快速提供难以置信地有用的诊断信息。从局部的角度来看，这可能是期望在学校发生爆发之前，及早发现儿童的腮腺炎或麻疹。从更全局的角度来看，这可能是期望病毒和细菌性疾病被更常规地测序，以便在早期阶段识别新的和可能有威胁的微生物。NHS宣布将采用一种能检测多达50种不同癌症的常规血液检测，这会加强公众的期望 (1, 2)。这样的可广泛使用的检测将是受欢迎的，特别是考虑到最近有报告说由于NHS工作人员短缺，多达34万名癌症患者面临延迟诊断。

The success and familiarity of widespread testing will perhaps leave patients with an expectation that ‘point of care’ diagnosis should be just as straightforward when it comes to other pathogens and diseases, not just COVID-19. Small samples of bodily fluids, which require little, if any, medical training to obtain, can be readily used to provide incredibly useful diagnostic information very quickly. From a local point of view, this could be an expectation that cases of mumps or measles in children are identified early, before an outbreak in schools takes hold. From a more global perspective, this could be an expectation that viral and bacterial diseases are sequenced more routinely to identify novel and possibly threatening microbes at an early stage. This public expectation may be reinforced by announcements that the NHS is moving towards adopting a routine blood test capable of detecting up to 50 different cancers (1, 2). A widely available test such as this would be welcome, particularly in view of recent reports that up to 340,000 cancer patients face later diagnosis due to NHS staff shortages.

癌症诊断不是NHS面对的唯一挑战。随着人口老龄化，病人可能出现多种疾病。颠覆历史上缓慢和成本密集的诊断，改善对微生物感染的快速识别，这对开发诊断产品的公司来说是个令人兴奋的机会窗口。然而，将新的诊断产品推向市场是高度竞争和研究密集型的，这可能使处于早期阶段的中小企业不堪重负。实验室费用、临床试验、监管部门的批准以及获得市场授权的漫长道路会使人感觉到将诊断产品推向市场仍是遥远的事情。

Cancer diagnosis is not the only challenge facing the NHS. With an aging population, patients are presenting with multiple conditions. Overturning historically slow and cost-intensive diagnosis procedures, and improving rapid identification of microbial infections, represents an exciting window of opportunity for companies developing diagnostic products. However, bringing new diagnostic products to market is highly competitive and research-intensive, which can be overwhelming for early stage SMEs. Laboratory costs, clinical trials, regulatory approval, and the long road to obtaining market authorisations can make it feel like bringing the diagnostic product to market remains on the distant horizon.

在通往市场的漫长道路上，拥有结构良好的知识产权战略可以使一切变得不同。在早期阶段确保获得知识产权，可以打开与合作者、投资者、承包商、制造商和供应商对话的大门，而不用担心保密问题。如果等得太久才申请知识产权保护，有可能被竞争对手设计出类似的创新，并通过先申请专利而"挖走"知识产权保护。在寻求获得诊断装置的专利保护时，值得注意的是，取决于技术，在不同的司法管辖区可能有不同的保护范围。例如，与在美国相比，直接与人体结合使用的诊断装置在欧洲的保护范围可能更受限。

Having a well-structured IP strategy can make all the difference when it comes to negotiating the long road to market. Securing IP at an early stage opens the door to conversations with collaborators, investors, contractors, manufacturers and suppliers, without having to worry about confidentiality issues. Waiting too long to file for IP protection runs the risk of a competitor devising a similar innovation, and ‘scooping’ IP protection by filing for a patent first. When looking to obtain patent protection for diagnostic devices, it is worth bearing in mind that different scopes of protection may be available in different jurisdictions, depending on the technology. For instance, the scope of protection available for diagnostic devices, which are used directly in conjunction with the patient’s body, may be more limited in Europe compared to the US.

当诊断装置采用诸如体液（如侧向流动检测和PCR检测）时，这些问题就不那么突出了，因为这些体液可以在远离人体的地方进行分析。因此，重要的是在研究和开发的早期阶段寻求知识产权专业人士的建议，以确保你的市场地位得到最广泛的保护。也不应忽视第三方现有知识产权的影响。与特定技术相关的现有知识产权可能阻碍诊断产品自由进入市场。为了重新打开进入市场的路径，中小企业可能在开发的很晚阶段还要开始谈判许可，或者甚至在已经为开发产品付出了艰辛努力的情况下被市场完全拒之门外。因此，在开发的早期阶段与知识产权专业人士讨论自由实施是很重要的。

These issues are somewhat less prominent when the diagnostic device employs, for instance, bodily fluids (e.g. lateral flow tests and PCR tests), which can be analysed away from the patient’s body. It is therefore important to seek the advice of an IP professional early in the research & development stage to ensure your market position can be protected in the broadest possible terms. The impact of existing IP protection owned by third parties should also not be overlooked. Existing IP relevant to a particular technology could preclude a diagnostic product being freely brought to market. To open the route to market back up, the SME may find themselves negotiating licences at a very late stage in development, or even being shut out of the market entirely, having already undertaken the hard work to develop a product. It is therefore important to speak to an IP professional to discuss freedom to operate in the market at an early stage of development.

毫无疑问，大流行已经永久改变了社会交往的结构——虽然有些人可能很容易地回到旧的世界，但其他人会继续戴口罩、更喜欢在户外就餐并在大流行过去以后有意识地保持社会距离 (3-6)。如果我们看看其他迫在眉睫的健康问题，围绕我们行为的永久性变化的猜测就可能不那么令人惊讶。抗生素耐药性的出现威胁着现代医学的基础。曾经可以治疗的感染可能突然变得无法治疗，对常规手术产生破坏性影响。在研究上历来被忽视的热带疾病，或尚未出现的可以跨物种传播的病原体，可能为下一个全球大流行打开大门。也许可以理解，当我们窥视未来可能出现的情况时，人们会持谨慎态度。然而，科学界和医学界在大流行期间调动资源的速度以及开发和上市多种疫苗的速度（该过程通常需要数年而不是数月），表明我们有能力解决迫在眉睫的问题，只要我们有意愿这样做。

Undoubtedly, the pandemic has permanently altered the fabric of social interaction – whilst some may find the transition back to the old world easy, others will likely continue to wear masks, prefer to dine al fresco, and be conscious of social distancing once the pandemic has passed (3-6). Speculations surrounding permanent changes in our behaviour may not be all that surprising when we look at other looming health problems. The emergence of antimicrobial resistance threatens the foundations of modern medicine. Infections that were once treatable, may suddenly become untreatable, with a devastating impact on routine surgery. Tropical diseases that have historically been neglected from a research perspective, or a yet to emerge pathogen capable of cross-species transmission, could open the door to the next global pandemic. Perhaps it is understandable why people are cautious when we peer into what the future may hold. However, the speed with which the scientific and medical communities mobilised resources during the pandemic, and the speed with which multiple vaccines were developed and brought to market (a process that normally takes in the order of years, not months), demonstrates that we have the capabilities to address looming issues now provided there is an appetite to do so.

毫无疑问，是深入的研究和高度集中的合作产生了应对大流行的惊人成就。大流行带来的社会和经济冲击应当激励我们所有人阻止其再次发生，而为应对新冠肺炎而建立的基础设施可以作为实现这一目标的跳板。希望随着我们今天看到的持续研究和合作，健康技术公司和机构将准备得更好地带我们走出下一次大流行（但愿不是在我们有生之年）。

Without question, intensive research and highly focussed collaboration has led to spectacular achievements in tackling this pandemic. The social and economic shock of the pandemic should galvanise us all into preventing a repeat occurrence, and the infrastructure that has been built to tackle COVID-19 could be used as a springboard to achieving this. Hopefully, with continued research and collaboration at an intensity we are seeing today, health technology companies and institutions will be all the more prepared to lead us out of the next pandemic (hopefully not in any of our lifetimes though).

1 https://www.dana-farber.org/newsroom/news-releases/2020/new-blood-test-can-detect-wide-range-of-cancers--now-available-to-at-risk-individuals-in-clinical-study-at-dana-farber/

2 https://www.theguardian.com/society/2021/jun/25/blood-test-that-finds-50-types-of-cancer-is-accurate-enough-to-be-rolled-out

3 https://www.nature.com/articles/d41586-021-01317-z

4 https://www.nature.com/articles/s41599-021-00749-2

5 https://www.bbc.co.uk/news/uk-56475807

6 https://www.theguardian.com/business/2021/jan/10/coronavirus-covid-outdoor-dining-restaurants