New human challenge trials are also recruiting volunteers
Written by | Yan Xiaoliu
Source | "Medical Community" public account
There were 36 young people aged 18-29 who had not been vaccinated against COVID-19, were in good health, and did not have any risk factors such as obesity and cardiovascular disease.
A group of British researchers poured coronavirus into their noses to see how the infection happened.
On March 31, local time, the "human challenge trial of the new crown virus", which is known as the world's first case, published the results in Nature Medicine.
The article was launched in preprint in the Nature Portfolio Journal on February 1 this year, entitled "Safety, Tolerance and Viral Dynamics of the Human Challenge Trial of the Novel Coronavirus". Compared to the time, Nature Medicine published an article that was peer-reviewed and had a more rigorous title, emphasizing "young people".
"Research is extremely valuable for understanding the infection process." Dr Christopher Chiu, a team leader and clinical professor in the Department of Infectious Diseases at Imperial College London, said that under safe and controllable conditions, infecting the human body with trace amounts of viruses has given scientists the opportunity to study and observe the initial progress of viral infection before the infected person has no symptoms.
"Challengers" sifted out of tens of thousands of people
According to the Nature Medicine article, 26,937 people signed up for the challenge, and 36 were selected. That's a significant reduction from the earlier media reports of studies that hoped to recruit 90 people.
Reuters reported that those in this age group were chosen because they were "the main factor driving the spread of the epidemic" at the time. As well, they are mostly mildly or asymptomatic after infection.
The research team used a slender nasal straw to drip the liquid containing the new coronavirus into the challenger's nasal cavity. The dose of the virus is equivalent to a tiny droplet sprayed by a confirmed person sneezing at the highest viral load.
The wild strain of the new coronavirus used in the study carries the D614G mutation. At the time of the study' inception, D614G had spread to become the most numerous mutation worldwide, and all emerging strains have since retained the mutation.
After being vaccinated, the challengers were admitted to a negatively pressured single room at the Royal Free Hospital in London, England, where they were medically monitored 24 hours a day. They were quarantined for at least 14 days and confirmed not contagious before being discharged from the hospital.
To further reduce risk, the study was divided into different phases. The earliest enrolled challengers were able to use the antiviral drug remdesivir preventively to reduce the chances of developing severe illness. The researchers also prepared anti-coronavirus monoclonal antibodies for treatment.
Eventually, remdesivir proved "unnecessary.". No one used monoclonal antibodies.
Infection progresses much faster than thought
The primary goal of this challenge trial is to find a dose that can cause mild infection in 50%-70% of subjects. Secondary objectives are to assess viral dynamics, etc. during infection.
"All goals were achieved." The article reads.
The analysis showed that 18 challengers were "implanted" with the virus and then tested for nucleic acid and confirmed infection.
The BBC analysis, which may be related to the design of the trial, gave participants very low viral loads, to why the other half were not infected. On the other hand, it may also stem from personal immunity. "That 50 percent of the uninfected will be one of the focuses of future research."
"This is really interesting place. We'd love to know those reasons. Chuk Jean said.
Among those infected challengers, the virus quickly exerted its power. The article "Nature-Medicine" details the virus dynamics information excavated and analyzed by the research team, including:
From the incubation period: In the past, it was generally believed that it took about 5 days from the first exposure to the virus to the onset of symptoms. But the challenge trial showed that infection progressed much faster than expected.
Throat swabs can be tested positive for nucleic acid as early as 40 hours after infection with the virus. It takes a slightly longer, about 58 hours, for a nasal swab to detect the virus.
When the virus is detected, the viral load rises sharply. The viral load of the throat swab peaks at 112 hours (about 4.7 days) after infection. Nasal swabs peak at 148 hours (about 6.2 days). At peak times, the viral load of nasal swabs is significantly higher than that of throat swabs.
From the perspective of rehabilitation: the average detoxification cycle of the challengers was about 10.2 days for the nose and about 8.7 days for the pharynx. Some of the challengers took slightly longer detoxifications, up to 12 days. This suggests that in the environment where a particular strain spreads, 14 days of isolation is sufficient to cut off the spread of the virus.
After 28 days of infection, some people's nasal and throat swabs can still detect positive nucleic acid, the proportion of which is 33% and 11%, respectively.
From the test: a twice-weekly rapid antigen test can diagnose positive before 70% to 80% of live viruses are produced. "The sensitivity of the first and second days is low, but it is correct and repeated daily, and once it is found positive, it can effectively block the spread of the virus." The study said.
Chukjean noted that the findings highlight some of the known knowledge of COVID-19 infections, "in particular, it strongly supports the importance of wearing masks and covering the mouth and nose." This can effectively reduce the spread of the virus and protect others. ”
"Long-term symptoms" of inability to relax
Of the 18 infected, two were asymptomatic. The remaining 16 people developed mild to moderate symptoms 2-4 days after infection, mainly manifested by nasal congestion, rhinitis, sneezing and sore throat.
The trial did not have serious unintended consequences, and not a single volunteer had lung involvement. The study says the results support the safety of human challenge trial models.
CNN reported that "the only thing that was a little worrying" was that 12 challengers developed some degree of olfactory impairment. 180 days after infection, 5 people still reported abnormal smell. Six months after the study ended, 1 person still had a sense of smell that was "improving and not returning to normal."
CNN cites another study that suggests this long-term loss of smell may be associated with brain changes.
Chuck Jean explained that the study designed long-term follow-up, including cognitive tests, to check its short-term memory and response rate. "We are still analyzing the data. This provides richer information. ”
"The challenge trial was very successful." According to Reuters, the research team said that by the end of 2022, using the Delta variant, a similar challenge trial is planned to analyze what kind of immune response can allow people to avoid secondary infections, and how the immune system works when they are secondary infections.
This new challenge was approved by the UK authorities in April 2021. In January, oxford university in the United Kingdom, one of the participating institutions in the research, published a "recruit challenger" message on its official website.
Helen Mcshane, a professor at the University of Oxford, said the volunteers were between the ages of 18 and 30, were in good health, and had either been infected and had no limit to vaccination, or had no natural history of infection but had been vaccinated.
Source:
2.First human challenge study of Covid-19 yields valuable insights about how we get sick. CNN
3.Volunteers needed for human challenge trial to study immune response to Covid-19. University of Oxford
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