新冠病毒可能对我们的大脑产生什么影响？

Surviving a pandemic isn't always the end of the story – some viruses can have health effects that linger on for decades, eventually leading to a range of devastating diseases.

在大流行中幸存下来不等于高枕无忧，有些病毒对健康的影响可能持续几十年，最终导致各种极具破坏性的疾病。

In the 1960s, epidemiologists studying the long-term prognosis of survivors of the 1918 Spanish Influenza began to notice an unusual trend. Those who were born between 1888 and 1924 – meaning they were either infants or in young adulthood at the time of the pandemic – appeared to have been two or three times more likely to develop Parkinson’s disease at some point in their life than those born at different times.

20世纪60年代，流行病学家在研究“1918年西班牙大流感”幸存者的预后时，开始注意到一种异常趋势。1888-1924年的出生者——意味着他们在疫情期间不是婴幼儿就是青壮年——与其他时期的出生者相比，在生命中的某一时刻患帕金森病的风险似乎增加两三倍。

It was a striking finding. For while the potential neurological consequences of flu infections have been documented by doctors for centuries – there are medical reports of this which date back to 1385 – the sheer scale of the Spanish Flu, which infected around 500 million people globally, meant scientists could lix a heightened risk of disease to the pandemic.

这是一个惊人的发现。几个世纪以来，医生一直在记录流感感染给神经造成的潜在后果——早在1385年就有这方面的医学报告——但“西班牙流感”的全球感染人数约5亿，规模之大意味着科学家可能将患病风险的增加与大流行关联起来。

In recent years, an elevated risk of Parkinson's has also been identified in the survivors of outbreaks of HIV, West Nile virus, Japanese encephalitis, Coxsackie, Western Equine virus and the Epstein-Barr virus. Neurologists attempting to understand why this happens believe that each of these viruses are capable of crossing into the brain, and in some cases damaging the fragile structures which control the co-ordination of movement, known as the basal ganglia, initiating a process of degeneration which can lead to Parkinson's.

近年来，科学家也发现大流行幸存者增加了患帕金森病的风险，诸如艾滋病病毒、西尼罗病毒、日本脑炎病毒、柯萨奇病毒、西方马型脑炎病毒、EB病毒。试图探究原因的神经病学家相信，以上每种病毒都能侵入大脑，在某些情况下使基底神经节受到破坏，这种脆弱的结构具有运动调节功能，结果引发神经退行，继而导致帕金森病。

Now scientists are keen to monitor whether the current pandemic will also trigger a higher rate of Parkinson's cases in decades to come.

现在科学家密切关注，当下的疫情是否也将导致未来十年帕金森发病率的增加。

"We don't know but we need to consider that this could become the case," says Patrik Brundin, a Parkinson's researcher at the Van Andel Institute, in Grand Rapids, Michigan. "There are several studies highlighting that people who have recovered from Covid often have long-term central nervous system deficits including loss of sense of smell and taste, brain fog, depression, and anxiety. The numbers are troubling."

“我们尚不清楚，但不排除这种可能性”，帕特里克·布伦丁说道，他是美国密歇根州大急流城范安德尔研究所的帕金森病科研人员。
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While Sars-CoV-2 can invade brain tissue, the scientific jury remains open on whether it will contribute to neurodegenerative disease. Coronaviruses are generally known as "hit and run viruses", because they tend to cause fairly short disease, even if this proves deadly in some cases. In contrast, DNA viruses such as Epstein-Barr can linger permanently in the body and are more associated with long-term illness.

尽管严重急性呼吸系统综合征冠状病毒2型（Sars-CoV-2）能侵入大脑，但是否造成神经退行性疾病，目前在科学上尚无定论。冠状病毒通常被称为“打了就跑病毒”，因为它们往往引起病程很短的疾病，尽管在某些情况下是致命的。相比之下，EB等DNA病毒能长期留存在体内，与慢性病有更密切的联系。

But there have been some indications in the past there might be more to coronaviruses than we perhaps suspect. In the 1990s, Canadian neurologist Stanley Fahn published a study which identified antibodies to the coronaviruses that cause the common cold in the cerebrospinal fluid of Parkinson's patients.

但过去的一些迹象表明，冠状病毒与帕金森病的联系可能比我们预想的更紧密。20世纪90年代，加拿大神经学家斯坦利·法恩发表过一篇研究报告，发现帕金森病患者的脑脊液中存在冠状病毒的抗体，这种病毒能引起普通感冒。

Over the past year, scientists like Brundin have been concerned by the emergence of a small handful of case studies describing patients who have developed what doctors term acute Parkinsonism – abnormalities such as tremors, muscle stiffness, and impaired speech – following Covid-19 infection. More research has found that some Covid-19 patients have disruptions in one of the body's most critical systems, known as the kynurenine pathway. This runs from the brain to the gut, and is used to produce a number of crucial amino acids required for brain health. But when it malfunctions, it can lead to the accumulation of toxins which are thought to play a role in Parkinson's disease.

去年，少数几份病例研究引起了布伦丁等科学家的关注，报告描述的病人患上医生所说的急性帕金森病——症状包括震颤、肌肉僵直、语言障碍——他们之前感染过新冠病毒。更多的研究发现，新冠病毒患者的犬尿氨酸通路受到破坏，它是人体最为关键的系统之一，从大脑延伸至肠道，用于生成许多大脑健康所需的关键氨基酸。一旦犬尿氨酸通路出现问题，就会导致毒素积累，这被认为是帕金森病的一个病因。
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Other neurologists, however, warn it is still far too early to draw any lix between Covid-19 and Parkinson's.

但是也有神经学家警告，现在就将新冠病毒与帕金森病关联起来为时尚早。

The 1918 flu pandemic was still affecting the health of the global population over 40 years later

1918年西班牙大流感爆发40年后，依然影响着全球人口的健康。

Alfonso Fasano, a neurology professor at the University of Toronto, points out that the cases of acute parkinsonism which have been described could simply involve patients who were already in the early stages of the disease, and the stress of being infected with Covid-19 simply accelerated or "unmasked" the symptoms. "So far, we're talking of about a dozen cases, usually lacking detailed information," he says. "It's true that what we call a post-encephalitic parkinsonism can occur after a viral infection, but not every pandemic is the same. The Spanish Flu was caused by a completely different virus."

加拿大多伦多大学神经病学教授阿方索·法萨诺指出，报告中的急性帕金森病例涉及的患者可能原本就处在帕金森病的初期阶段，感染新冠病毒造成的精神压力只是加快或暴露了症状。“到目前为止，我们正在探讨的病例约有10多个，通常欠缺详细资料”，他说道。“病毒感染确实可能导致我们所说的脑炎后帕金森综合征，但不是每一次大流行都这样。西班牙流感是由另一种完全不同的病毒引起的”。

However many feel that there is a need for continued monitoring of any Parkinson’s-like symptoms which emerge in people who have previously been infected with Covid-19, in case the coming years reveal a gradual spike in cases.

但许多科学家认为，有必要继续关注先前感染过新冠病毒的患者出现类似帕金森病的症状，以防未来几年帕金森病例会逐渐增加。

But Parkinson's is not the only concern. Experts around the world are trying to figure out if Covid-19 will induce a hidden wave of other illnesses, related to the disruption Sars-CoV-2 causes to the human immune system. If this pans out it would have major public health implications, but it could also help us find new ways of detecting these diseases at an early stage, and even pave the way to new treatments and vaccines.

但帕金森病不是唯一的担忧。世界各地的专家都在试图弄明白，新冠病毒是否将引起其他隐匿性疾病，这些疾病与新冠病毒对人体免疫系统造成的破坏有关。如果取得进展，这将对公共健康产生巨大影响，还有助于我们找到新方法诊断出这些尚处在初期阶段的疾病，甚至为新型疗法和疫苗铺平道路。

The diabetes dilemma

糖尿病困境

In the spring of 2020, Francesco Rubino, a metabolic and bariatric surgeon at Kings College London, began to hear an increasing number of reports about Covid-19 patients coming into hospital with unusually high blood sugar levels, even though they had no previous history of diabetes.

2020年春季，伦敦大学国王学院的减重代谢外科医生弗朗西斯科·鲁比诺，开始听说这样的病例报告越来越多，即入院的新冠病毒患者伴有异常的高血糖症状，即便他们过去没有糖尿病史。

At the same time, doctors were also noticing that patients who already had diabetes appeared to be particularly vulnerable to the disease. Rubino was curious to see whether this strange relationship was a sign that Covid-19 was directly impacting the pancreas, a complex organ which contains beta cells for producing insulin, the hormone that helps the body metabolize sugar molecules from the blood.

与此同时，医生还注意到已经患有糖尿病的患者似乎特别容易感染新冠肺炎。鲁比诺好奇这种奇怪的关联是否证明新冠病毒会直接影响胰腺，这种复杂器官包含的β细胞生成胰岛素，这种激素帮助人体代谢血液中的糖分子。

He set up a global database called the CovidDiab registry to follow these patients, and find out what happened to them. So far they have been tracking 700 cases over the past year, and the hope is that their data might help solve an enduring problem that has intrigued scientists for many years, namely whether viruses can directly trigger type 1 diabetes.

他建立了全球数据库“新冠糖尿病登记处”随访这些患者，想弄明白他们发生了什么情况。到目前为止，他们在过去一年里随访了700个病例，希望这些数据有助于解决多年来一直困扰科学家的一个问题，即病毒是否会直接导致1型糖尿病？
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A number of viruses have been lixed to the rare neurological condition Guillain-Barré syndrome. One is Zika, which may have led to a spike in cases in 2015

许多病毒与罕见的神经系统疾病吉兰-巴雷综合征有关联，其中包括寨卡病毒，可能在2015年导致病例激增。

In the past, associations have been made between type 1 diabetes – a chronic condition which typically develops in childhood or adolescence as patients' pancreases become steadily unable to produce insulin – and various viruses such as Coxsackie B, rubella, cytomegalovirus, and mumps. Scientists suspect that these viruses may be capable of infecting the pancreas, either by escaping from the lungs or leaking out of the gut and into blood vessels. In 2015, researchers at the Oslo Diabetes Research Centre discovered a persistent, low grade viral infection in beta cells extracted from pancreas tissue biopsies of newly diagnosed type 1 diabetes patients, but there have been too few cases to establish concrete proof.

在过去，科学家曾将1型糖尿病——通常在儿童或青少年时期患有的慢性病，患者的胰腺逐渐丧失分泌胰岛素的功能——与各种病毒相关联，诸如柯萨奇病毒B型、风疹病毒、巨细胞病毒、腮腺炎病毒。科学家怀疑这些病毒可能会感染胰腺，途径是从肺部或肠道逃逸进入血管。2015年，奥斯陆糖尿病研究中心的科研人员从新确诊的1型糖尿病患者的胰腺活检中提取出β细胞，发现存在持续性的轻度病毒感染，但由于病例太少而无法证据确凿。

"There's been epidemics before which have been associated with new cases of diabetes," says Rubino. "But this lix has been based on a handful of medical reports. So we're hoping that by looking at several hundred cases, we might see an association which is more informative."

“科学家曾经将流行病与新增的糖尿病病例相关联”，鲁比诺说道。“但这种关联是基于少数的医疗报告，所以我们希望通过研究几百个病例，可能发现信息量更大的关联”。
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Since the beginning of the Covid-19 pandemic, there have already been repeated indications of an abnormal spike in type 1 diabetes cases. By the summer of 2020, hospitals in North West London were already reporting double the number of cases they would typically see, while a paper in Nature earlier this year found Covid-19 survivors in the US were around 39% more likely to have a new diabetes diagnosis in the six months following infection compared to non-infected individuals.

自新冠疫情爆发以来，不断有迹象表明1型糖尿病的病例数量异常增加。到了2020年夏季，伦敦西北区的各家医院报告的病例数量比往常增加一倍，今年年初《自然》杂志上的一篇论文发现，美国的新冠肺炎幸存者在感染后的六个月内，被确诊为糖尿病的几率比非感染者高39%左右。
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Scientists are now trying to prove that Covid-19 is actually directly contributing to this rise in cases. Shuibing Chen, a stem cell biologist at Weill Cornell Medicine, feels there is evidence which suggests that the virus can attack beta cells, and also generate inflammation in the pancreas and other organs, causing damage to various systems which control blood sugar levels.

现在科学家试图证明，新冠肺炎病毒确实直接导致了糖尿病病例的增加。威尔康奈尔医学院的干细胞生物学家陈水冰认为，病毒能攻击β细胞，并引起胰腺和其他器官发炎，从而使控制血糖水平的各个系统受到损害。

"We have detected viral antigens in human pancreatic beta cells in autopsy samples of Covid-19 patients, which supports the role of direct infection," Chen says.

“我们在新冠肺炎患者的尸检样本中，发现人类胰腺的β细胞中存在病毒抗原，证明了病毒直接感染的影响”，陈水冰说道。

But not everyone is so convinced. Others point out that patients appearing to develop diabetes as a result of Covid-19 could actually be incurring pancreas damage due to intensive steroid treatment while in hospital. Or they may have already been in the early stages of developing diabetes, and Covid-19 again may simply have unmasked the disease.

但不是每个人都深信不疑。有人指出患者的糖尿病看似由新冠肺炎导致，实则住院期间接受的类固醇强化治疗可能对胰腺造成了损害。还有可能患者已经处在糖尿病初期阶段，新冠肺炎可能只是暴露了病情。

It's thought that certain viruses can trigger an immune response which later increases the risk of a person developing Parkinson's disease

科学家认为某些病毒能引起免疫反应，继而增加患帕金森病的风险。

"There have been some reports arguing that Sars-CoV-2 can not only directly infect beta cells, but also might kill them," says Matthias Von Herrath, a professor of autoimmunity at the La Jolla Institute for Immunology. "A follow up report, however, argues against the notion that it commonly affects beta cells. So, the jury as to how specific and dangerous it is in causing beta cell functional loss is still out."

“有报告指出，新冠病毒不仅直接感染β细胞，还可能直接杀死它们”，拉霍亚免疫学研究所自体免疫学教授马提亚·凡·赫拉特说道。“然而，一篇随访报告驳斥了新冠肺炎病毒普遍影响β细胞的观点，所以新冠病毒导致β细胞功能丧失的确切性和危害性尚不明确”。

Over the coming months, the hope is that the CovidDiab database will yield some more concrete answers. "We don't expect to be able to answer all the questions, but we hope to learn a lot from these 700 cases which probably represents the largest cohort of virus-related diabetes," Rubino says. "How plausible is it that Covid might have been behind these cases? Is there a direct mechanism and if so, what is it?"

在接下来的几个月里，但愿CovidDiab数据库将给出更确切的答案。“我们不指望能够解答所有的问题，但希望从这700个病例中获益良多，这可能是数量最多的病毒相关糖尿病病例”，鲁比诺说道。“新冠病毒可能是这些病例的罪魁祸首，可信度有多大？是否存在直接致病机制？如果存在，又是怎样一种机制”？
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But type 1 diabetes is not the only autoimmune disease being lixed to Covid-19. Over the past year, a number of reports have associated Sars-CoV-2 infection with other autoimmune disorders such as Guillain–Barré Syndrome, a rare and serious condition in which the immune system attacks the nerves, causing numbness, issues with balance and coordination, weakness, and pain, and sometimes paralysis..

但是，1型糖尿病不是唯一与新冠病毒相关联的自体免疫性疾病。在过去一年里，医学报告将新冠病毒感染与其他自体免疫性障碍相关联，譬如吉兰-巴雷综合征，这是一种严重的罕见病，免疫系统攻击神经系统，导致麻木、平衡与协调下降、无力、疼痛、有时导致瘫痪。

Scientists believe that patients who have been admitted to hospital with Covid-19 are particularly prone to going on to develop such complications as they are more likely to have auto-antibodies in their blood – a form of protein produced by the immune system which is directed against the body's own tissues, leading to complications. A consortium of scientists at the University of Birmingham are now following a cohort of individuals who had been severely ill with Covid-19, to see how many develop longer term autoimmune problems and what makes certain people particularly vulnerable.

科学家认为，入院的新冠肺炎患者特别容易患上这类并发症，因为他们的血液中容易出现自身抗体——这种由免疫系统分泌的蛋白质会对抗自体组织，导致并发症。英国伯明翰大学的科学家们正在随访一批新冠肺炎重症患者，看看有多少患者出现了长期的自体免疫性问题，什么原因导致某些人特别容易患上这类疾病。

"We can't predict the future," says Russell Dale, who researches autoimmune illnesses at the University of Sydney. "But there are a number of precedents of infectious diseases leading to inflammatory and autoimmune problems."

“我们无法预知未来”，来自悉尼大学研究自体免疫性疾病的罗素·戴尔说道。“但是，有许多传染病引起炎症和自体免疫性问题的先例”。

Diagnostics and vaccines

诊断学与疫苗

The prospect of Covid-19 leading to a silent surge of chronic illnesses is a sobering one, but if conclusive lixs can be established between viral infection and different conditions, it could transform the way we look for and treat many of these diseases in future.

新冠肺炎可能引起无症状的慢性病激增令人深思，但如果病毒感染与各种疾病之间的关联得到确证，将来可能改变我们诊断和治疗这些疾病的方式。

In the case of type 1 diabetes, scientists are particularly keen to study exactly what happens after beta cells become infected with Sars-CoV-2 to see if there is a way to prevent their destruction, and hence halt the onset of the disease before it fully develops. "Understanding the lix between viral infection and type 1 diabetes might facilitate early diagnosis and prevention," says Chen.

至于1型糖尿病，科学家非常热衷于研究β细胞在感染新冠病毒后究竟发生了什么，看是否有办法阻止新冠病毒造成破坏，从而在疾病尚未完全成形之前防患于未然。“弄明白病毒感染与1型糖尿病之间的关联可能有助于早期诊断与预防”，陈水冰说道。

Coxsackie B virus has been lixed to the development of type 1 diabetes – and now scientists are wondering if Covid-19 could also make people more susceptible

柯萨奇病毒B型与1型糖尿病的发病有关联，现在科学家想弄明白，新冠病毒是否也能使人更容易患1型糖尿病。

Knut Dahl-Jørgensen, a consultant in pediatric endocrinology and diabetes at the Oslo Diabetes Research Centre, told the BBC his colleagues are initiating a clinical trial to see whether antiviral treatment can help protect the pancreas in children who have been newly diagnosed with type 1 diabetes.

奥斯陆糖尿病研究中心的儿科内分泌与糖尿病顾问克努特·达尔-约根森向BBC透露，他的同事正在启动临床试验，研究抗病毒治疗是否有助于保护新确诊为1型糖尿病儿童患者的胰腺。

Chen is also leading a project which involves sifting through a large library of different chemical compounds to see if any can make beta cells more resilient to viral attack. So far they have already identified one particular compound called trans-ISRIB, which appears to be capable of protecting the insulin-producing capacities of beta cells when infected with Sars-CoV-2 in a petri dish. While this is not yet approved by regulators nor tested in humans, and so cannot be used in Covid-19 patients experiencing blood sugar abnormalities at the moment, Chen hopes that in future it could be administered as a preventative drug for vulnerable individuals in the aftermath of infection.

陈水冰也在领导的项目是筛选大量不同的化合物，研究哪种化合物能够增强β细胞对病毒攻击的抵抗力。到目前为止，他们发现了一种名为trans-ISRIB的独特化合物，当培养皿中的β细胞感染新冠病毒时，它似乎能保护β细胞分泌胰岛素的功能。该化合物尚未得到监管部门的批准或经过人体试验，所以目前无法提供给血糖水平异常的新冠肺炎患者使用，但陈水冰希望，将来感染新冠肺炎后易患糖尿病的个人可将其作为预防性药物来使用。

A strong lix between Covid-19 and different autoimmune conditions could also encourage the development of protective vaccines against other viruses which have been previously associated with these illnesses. Researchers at the Karolinska Institute, Tampere University, and the University of Jyväskylä have developed a potential vaccine candidate which protects against all six strains of Coxsackie B, and has been shown to prevent mice from developing virus-induced type 1 diabetes.

新冠肺炎与自体免疫性疾病之间的紧密联系也有助于研发疫苗，预防曾经被认为与这些疾病有关的其他病毒。来自卡罗林斯卡学院、坦佩雷大学、于韦斯屈莱大学的科学家研发出一种潜在的候选疫苗，能够预防柯萨奇病毒B型的所有6种毒株，并证明能够预防老鼠患上病毒诱发的1型糖尿病。

Gunnar Houen, an immunologist at the State Serum Institute in Copenhagen, believes it could also lead to further investment in vaccines against Epstein-Barr, a virus which has been associated with the development of rheumatoid arthritis and multiple sclerosis, as well as certain cancers.

来自哥本哈根国家血清研究所的免疫学家贡纳·保延认为，这还能促进EB病毒疫苗得到更多投资，该病毒与类风湿性关节炎、多种硬化症、以及某些癌症有关联。

"Vaccines are very likely to be effective against Epstein-Barr if given early enough, as most people are infected by this virus during the first one or two years of life," says Houen. "There will be a market for this, since the associated diseases cause as much or even more harm as Covid-19."

“如果尽早接种疫苗，很可能对EB病毒起到预防作用，因为大多数人会在出生后的头一两年感染这种病毒” 保延说道。“未来会有市场前景，因为相关疾病造成的危害不亚于甚至超过新冠肺炎”。

In the meantime, scientists hoping that the coming months and years will reveal more about the propensity of Covid-19 to trigger each of these illnesses.

与此同时，科学家希望在未来的年月里，揭示更多关于新冠肺炎诱发上述种种疾病的倾向性。

"All these questions will not be answered tomorrow, or in the next couple of months, but over the next year we hope to be able to look into this data and begin to answer certain questions, start to see some patterns and maybe have some answers," says Rubino.

“所有这些问题将在明天或未来几个月里得到答案，但在接下来的一年里，我们希望能够研究这些数据，开始解答某些问题，发现某些致病机制，可能会得到一些答案”，鲁比诺说道。