Why does covid-19 have such varied manifestations?
新冠肺炎的症状为何如此多变?

【双语】变形附体 The body snatcher-书迷号 shumihao.com

ACCORDING TO England’s National Health Service the signs that someone has contracted the novel coronavirus SARS-CoV-2 are a high temperature or a new, continuous cough. This is certainly true for a majority of patients, but it is not so for a sizeable minority. Papers published in recent weeks present the new virus as having many faces. This is in stark contrast to the way in which influenza, another primarily respiratory disease, behaves—and it makes SARS-CoV-2 all the more dangerous. It also raises the question of why this virus’s symptoms are so protean.

根据英国国家医疗服务体系(NHS)的说法,感染新冠病毒的症状是发烧或新发的持续咳嗽。大多数患者确实有这些症状,但相当一部分患者不然。最近几周发表的论文表明这种新病毒有很多面相。这与另一种主要呼吸道疾病流感的特点形成了鲜明对比——也让新冠病毒愈发危险。这同时也引发了疑问:为什么这种病毒的症状如此变化无常?

For decades, influenza has been referred to as “an unvarying disease caused by a varying virus” because of its tendency to mutate every year and yet still cause the same symptoms of rapid-onset fever, malaise, headaches and coughing. Indeed, a review of influenza papers published in 2018 by John Paget of the Netherlands Institute for Health Services Research, showed that even when all of the different influenza types (A or B) and subtypes (H1N1, H3N2, etc) were analysed, there were few differences in the ways they presented clinically. Literature on SARS-CoV-2 suggests, by contrast, that this virus is a master of disguise.

几十年来,流感一直被称作“由一种不断变异的病毒引发的症状不变的疾病”,这是因为尽管流感病毒往往每年都发生变异,它引发的症状却仍然是急性的发热、乏力、头痛和咳嗽等。荷兰卫生服务研究所(Netherlands Institute for Health Services Research)的约翰·佩吉特(John Paget)回顾了2018年发表的有关流感的论文后发现,即使把不同的流感类型(甲型或乙型)和亚型(H1N1、H3N2等)都一起分析,它们的临床症状也没什么差异。相比之下,有关新冠病毒的文献表明这种病毒是伪装大师。

For example, Anthony DeBenedet, a doctor at St Joseph Mercy Health System in Michigan, reports in the American Journal of Gastroenterology that in early March, following a trip down the Nile, a 71-year-old woman arrived at his emergency department with bloody diarrhoea. She suffered with this condition for five days, while also experiencing abdominal pains and nausea. But her temperature was normal and her breathing good, so covid-19 was not suspected. Yet when he and his colleagues examined samples of her stools for signs of the sorts of bacterial infections that are likely to be picked up in Egypt, they found none. They also saw no beneficial effects from the antibiotics they were administering. They therefore started to wonder whether something else might be going on. It was only on the fourth day of the woman’s stay at the hospital, her ninth day of illness, when she developed a cough, that they tested her for SARS-CoV-2 and confirmed the virus’s presence in both her nasal tissues and her stools.

例如,密歇根州圣约瑟夫·梅西医疗系统(St Joseph Mercy Health System)的医生安东尼·德本尼德(Anthony DeBenedet)发表在《美国胃肠病学杂志》(American Journal of Gastroenterology)上的文章中有这样一个病例:3月初,一位71岁的妇人从尼罗河沿线旅行回来后,因血性腹泻来到他的急诊室。她的这个症状已持续了五天,同时伴有腹痛和恶心。但她体温正常,呼吸顺畅,因此没有怀疑到新冠肺炎上面去。但是,当他和同事化验了她的粪便样本后,并没有发现任何在埃及容易“中招”的那些细菌感染的迹象。而且给她开了抗生素也没什么用。因此他们开始怀疑是其他问题。直到这位女患者住院的第四天,也就是患病的第九天,她开始咳嗽了,他们这才对她做了新冠检测,并证实她的鼻腔组织和粪便中都存在这种病毒。

Dr DeBenedet’s findings are far from unique. Patients brought into hospital with all the symptoms of a heart attack have later been found to be suffering from cardiac inflammation caused by the virus. It has also demonstrated that it can begin as a kidney infection, or even as meningitis, before sometimes going on to cause its characteristic respiratory problems.

德本尼德的发现远非特例。有的病人因为全然是心脏病发作的症状送医,后来却发现是新冠病毒引起的心脏炎症。感染的初期症状还可能是肾脏感染、甚至是脑膜炎,之后一些人才会出现典型的呼吸系统问题。

Variations on a theme

主题变奏曲

Precisely why SARS-CoV-2 manifests itself in so many ways while all of the various strands of influenza present the same symptoms is not clear. But there are several theories. One proposed by Stanley Perlman, an immunologist at the University of Iowa, is that in actual fact, nothing odd is really going on. The novel virus’s many faces are being noticed merely because it is a new disease and dangerous, and so is being studied intensely. He postulates that if influenza were looked at with equal intensity, it might also be shown to manifest in other ways—as a mild winter stomach infection, for example.

究竟为何新冠病毒的症状如此多种多样,而所有不同类型的流感症状相同,目前尚不清楚原因。但有几种理论。爱荷华大学的免疫学家斯坦利·珀尔曼(Stanley Perlman)认为实际上这并不奇怪。人们会注意到新冠病毒面孔百变,仅仅是因为它是一种新的疾病而且危险,因而被深入研究。他推测,如果对流感也做同样细致的研究,可能也会发现其他症状,例如冬季轻度的胃部感染。

An idea suggested by William James, a virologist at the University of Oxford, is that the two-phase activity of SARS-CoV-2, whereby it starts in the upper respiratory tract and then migrates deep into the lungs, is the critical factor that allows it to travel around the body. “Influenza rarely gets deep into the lungs,” he says. “This new virus gets down there all the time.” Since the lungs are designed to move gases in and out of the bloodstream (their highly vascularised airs sacs have a collective surface area of about 50 square metres), viruses find it easy to make a similar journey.

牛津大学的病毒学家威廉·詹姆斯(William James)的看法是,新冠病毒的活动分两个阶段,从上呼吸道开始,然后深入到肺部,这是它能到达全身各处的关键原因。“流感很少发展到肺部,”他说,“而新冠病毒总是能进入肺部。”由于肺的功能是运输气体进出血液(被血管环绕的肺泡的总表面积约为50平方米),病毒很容易展开相同的旅程。

Dr Perlman agrees that this notion may be correct, but points out that the only way to be sure is to take samples from places other than the respiratory tract, in people suffering from early stages of the infection, to see if virus migration depends on getting to the lungs first. As for why the disease sometimes makes its initial appearance in the digestive system, as it did in Dr DeBenedet’s patient, this is probably because ACE2, the cell-surface protein that SARS-CoV-2 binds to, is abundant in the gut as well as the lungs. How the virus gets through the highly acidic stomach unharmed is unknown. But clearly it can, and does.

珀尔曼认为这种看法可能是对的,但他指出,若要完全确定这一点,唯一的方法是从处于感染早期的患者的呼吸道以外的地方取样,以查看病毒在迁移前是否一定会先进入肺部。至于为什么有时这种病会像德本尼德的患者那样先出现消化系统的症状,则可能是因为ACE2这种新冠病毒与之结合的细胞表面受体蛋白在消化道和在肺部一样广泛存在。尚不清楚病毒如何能经过酸性很高的胃部而不受损伤,但显然它有这个能力,也确实发生了。

ACE2 is also found in the kidneys and the heart, which may help explain why symptoms manifest there, as well. By contrast, the entry molecules preferred by influenza viruses are almost exclusive to the upper respiratory tract. Knowing all this may make identification of the early stages of covid-19 easier, and thus help to ease the plight of future cases like that of Dr DeBenedet’s patient.■

ACE2还存在于肾脏和心脏中,这可能有助于解释为什么那些地方也会出现症状。相反,流感病毒在进入人体时的受体分子几乎是上呼吸道所独有的。了解这些也许会让医生更容易识别新冠肺炎的早期症状,从而帮助像德本尼德的病例那样的患者。