首个新冠病毒人类挑战实验产生了关于我们如何患病的有价值见解

First human challenge study of Covid-19 yields valuable insights about how we get sick

It takes just a tiny virus-laden droplet -- about the width of a human blood cell -- to infect someone with Covid-19.使人得新冠仅需一小滴与人的血细胞大小的含病毒的飞末。

That's just one of the findings from research that deliberately infected healthy volunteers with the SARS-CoV-2 virus. The findings were published Thursday in the journal Nature Medicine.

这是故意用新冠病毒感染志愿者研究的发现之一，这些研究发现周三在<自然医学>杂志发表了。

Challenge studies can be controversial because they involve intentionally giving someone a virus or other pathogen in order to study its effects on the human body. Even with safeguards in place, there's an element of risk, particularly when studying a new virus.

But they are also hugely valuable for understanding the course of an infection.

人体挑战实验是有争议的，因为它们涉及：为了研究人体的反应，故意用病毒或病原体来感染人。即使有保护措施，仍然有一些冒险成分，特别是研究新病毒。但是这些试验在理解感染过程方面有巨大价值。

"Really, there's no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing," said lead study author Dr. Christopher Chiu, an infectious disease physician and immunologist at Imperial College London.

实际上，没有其他类型的研究能做到这些，因为通常情况下，只有患者有症状才会引起你的注意，所以你会错过感染开始的前期几天。

Volunteers were carefully screened

仔细筛选志愿者

The study began in March 2021. The 36 volunteers were between the ages of 18 and 30. They were allowed to participate only if they didn't have any risk factors for severe Covid-19, such as being overweight, having reduced kidney or liver function, or having any heart, lung or blood problems. They also signed an extensive informed consent form to participate.To further minimize the risks, researchers conducted the study in phases. The first 10 infected volunteers got the antiviral drug remdesivir to reduce their chances of progressing to severe disease. Researchers also had monoclonal antibodies at the ready in case anyone took a turn for the worse. Ultimately, the remdesivir proved unnecessary, and researchers never had to give anyone antibodies.

The volunteers got a tiny drop of fluid containing the originally detected strain of the virus through a long, thin tube inserted into their nose.

They were medically monitored 24 hours a day and stayed for two weeks in rooms at London's Royal Free Hospital that had special air flow to keep the virus from escaping.

Half were infected

A total of 18 participants became infected, two of whom never developed symptoms. Among the people who got sick, their illnesses were mild. They had stuffy noses, congestion, sneezing and sore throats.

Most of the study participants who caught Covid-19 -- 83% -- lost their sense of smell, at least to a degree. Nine couldn't smell at all.

This now-well-known symptom got better for most people, but six months after the study ended, there's one person whose sense of smell isn't back to normal but is improving.

That's a concern because another recent study found that this loss of smell was tied to changes in the brain.

Chiu says the researchers gave the participants cognitive tests to check their short-term memory and reaction time. They're still looking at that data, but he thinks those tests "will really be informative."

None of the study volunteers developed lung involvement in their infections. Chiu thinks this is because they were young and healthy and inoculated with tiny amounts of virus.

Beyond the loss of smell, no other symptoms persisted.

A closer look at infection as it moves through the body

Under these carefully controlled conditions, researchers were able to learn a lot about the virus and how it moves through the body:在这些仔细控制的条件下，研究人员对病毒了解许多，以及它如何进入人体

• Tiny amounts of virus, about 10 microns -- the amount in a single droplet someone sneezes or coughs -- can make someone sick.微量病毒，一个喷嚏或咳嗽的飞末中的病毒量，就能让人致病。
• Covid-19 has a very short incubation period. It takes about two days after infection for a person to start shedding virus.新冠病毒潜伏期非常短。大概感染后两天，患者就能排出病毒
• People shed high amounts of virus before they show symptoms (confirming something epidemiologists had figured out).患者出现症状前就排出高量病毒
• On average, the young, healthy study volunteers shed virus for 6½ days, but some shed virus for 12 days.通常，年轻健康的志愿者排出病毒6.5天，但一些人排出病毒达12天。
• Infected people can shed high levels of virus without any symptoms.无症状感染者可排出大量病毒
• About 40 hours after the virus was introduced, it could be detected in the back of the throat.大约感染病毒后40小时，在咽喉壁就能检测到。
• It took about 58 hours for virus to show up on swabs from the nose, where it eventually grew to much higher levels.
• 大约58小时，鼻咽拭子就能出现病毒
• Lateral flow tests, the rapid at-home kind, work really well for detecting when a person is contagious. The study found that these kinds of tests could diagnose infection before 70% to 80% of viable virus had been generated.
• Lateral flow tests，一种能在家里做的快速检测，用来筛查患者是否有传染性效果很好。

Chiu says his study emphasizes a lot of what we already know about Covid-19 infections, not least of which is why it's so important to cover both your mouth and nose when sick to help protect others.

本研究一证实了许多我们已知的有关新冠病毒感染，至少说明了为什么患者通过遮住嘴巴和鼻子来保护其他人如此重要。

More challenge studies planned

This challenge study was so successful that Chiu plans to do it again, this time with vaccinated people infected with the Delta variant to study their immune response.

He says his team also plans to continue studying the people who didn't get sick.

"That's what's really interesting," he said. About half of the study participants never got sick and never developed antibodies, despite getting exactly the same dose of the virus.

Everyone was screened for antibodies to closely related viruses, like the original SARS virus. So it wasn't cross-protection that kept them safe; it was something else.

"There are lots of other things that help protect us," Chiu said. "There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems, and they are likely to have been contributing to them not being infected, and we're really interested in trying to understand what those are."

Understanding what other factors may be at play could help us provide more generalized protection to people in case of a future pandemic.

详见 https://edition.cnn.com/2022/03/31/health/first-challenge-study-covid-19/index.html