Why does covid-19 have such varied manifestations?
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.
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.
Variations on a theme
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.
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.
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.
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.■