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34 people were actively infected with COVID-19: Test Results Announced!
The world’s first! 34 people were actively infected with COVID-19, the results of the human challenge test were announced
On February 1, 2022, a preprinted paper titled Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge was published in Nature Portfolio Journal , announcing the results of the world’s first human challenge trial for COVID-19.
Screenshot of the paper
The study “vaccinated” 34 healthy young adults who had not been infected with the new coronavirus and had not been vaccinated with a strain that was close to the original new coronavirus.
The paper explains that this is to explore the detailed process of virus infection in low-risk groups and provide a reference for community transmission driven by asymptomatic or mild infection. At the same time, indicators such as viral dynamics, immune responses, transmission dynamics, and viral shedding can be accurately measured.
According to previously published information, the research was a joint collaboration between Imperial College London, the Royal Free National Health Service London Foundation and hVIVO, and the British government also provided 33.6 million pounds (about 300 million yuan) of financial support for this.
What do the research results say?
The trial results came from 34 healthy young people aged 18 to 29 who had neither had the COVID-19 nor been vaccinated.
In early 2021, the researchers “vaccinated” the subjects with a strain close to the original coronavirus via intranasal drops. Subjects are planned to be quarantined for at least 14 days after vaccination until they meet virological discharge criteria, and followed for 1 year to assess long-term symptoms, including olfactory and neurological impairments.
The researchers carefully designed the virus dose for the trial.
There have been studies on human challenge tests for other respiratory infectious diseases such as influenza, but because most people have been infected with these viruses and have resistance, the virus dose used in the test is relatively high. However, in this human challenge trial, in the face of the new coronavirus, the subjects were almost a blank sheet of paper, so the dose chosen by the researchers was not high, and it was planned to use this dose to infect 50-70% of the people.
After receiving the virus, each subject stayed in a separate room with negative pressure to ensure that the virus would not spread. In the end, 18 of the 34 subjects were confirmed to be infected with the COVID-19, accounting for 53%.
Among the 18 people who were infected, what did the researchers observe?
First, the study tracked how the virus replicated. It was found that among infected subjects:
– Quantitative detection of the virus by qPCR can be detected as early as 40 hours (about 1.67 days) after inoculation in throat swabs, and as early as 58 hours (about 2.4 days) after inoculation in nasal swabs;
– The viral load in pharyngeal swabs peaked at 4.7 days after infection, while in nasal swabs at 6.2 days, but the peak viral load level in nasal swabs was higher than that in throat swabs, which also confirms that nucleic acid testing has Nasopharyngeal sampling is justified ;
– The duration of live virus in an infected person is roughly the same as the duration of rapid antigen positive, indicating that antigen testing can be used to diagnose whether a person is infectious and can also help decide when to release quarantine.
Interestingly, at the expected end of 14 days, some subjects still tested positive for nucleic acid, so they had to stay for another 5 days. After 28 days, 33% and 11% of people tested positive for nucleic acids in the throat and nasopharynx. However, at this point they are no longer contagious.
The second is the monitoring of antibodies produced by infected people. The researchers collected the serum of infected people on the 14th and 28th days after “inoculation” with the virus, and found that:
– Neutralizing antibodies reached 425 at 14 days, but doubled to 864 at 28 days.
– IgG antibodies to S protein were 193 and 1549 at 14 and 28 days.
In this way, neutralizing antibodies may peak at 28 days post-infection.
Third, the researchers looked at the symptoms of infected people and found that:
– 89% of people infected with the virus developed symptoms, all infected people had mild to moderate symptoms, the infection was limited to the upper respiratory tract, and there were no changes in the lungs. But there was no quantitative correlation between viral load and symptom severity, and viral load was high even in asymptomatic infections.
– 16 infected people developed symptoms concentrated in 2 to 4 days after virus infection was detected;
– 12 infected individuals developed some degree of olfactory disturbance. Half a year after infection, 5 people still reported that the sense of smell was not fully recovered, but the degree was relatively mild.
A Controversial Trial
In fact, the COVID-19 human challenge test has appeared in the public eye as early as the beginning of the epidemic.
On March 31, 2020, Harvard epidemiologist Marc Lipsitch suggested in the “Journal of Infectious Diseases” that volunteers should be used to conduct “challenge trials” instead of traditional vaccine phase III experiments- that is, volunteers are actively given COVID-19s . virus, rather than passively waiting for the infection to occur naturally.
Mark suggested that young and middle-aged volunteers who have not been infected with the new coronavirus should be selected and randomly divided into groups, half of which will be vaccinated and the other half will be given a placebo. These volunteers were then exposed to the new coronavirus to see how much protection the vaccine provided. All of these volunteers were tested in isolation and guaranteed the best medical conditions in case of serious illness.
Human challenge trials have two main advantages.
First, the results are much faster than conventional clinical phase III trials . For the world at that time, an effective COVID-19 vaccine was urgently needed to save lives;
Second, human challenge trials only require dozens to hundreds of people , and do not need to recruit hundreds of thousands of people like clinical phase III trials.
However, this idea has been accompanied by controversy since its inception – actively infecting healthy people with the new coronavirus, is this really in line with medical ethics?
In this regard, Professor Mark, who originally proposed the proposal, believes that similar behaviors already exist in society. Such as firefighters rushing into a burning building, or relatives donating live organs to relatives, or healthy volunteers participating in vaccine toxicity experiments, all of which have known risks and no benefit to them.
On May 10, 2020, the WHO issued a special document for HCT of the new coronavirus vaccine, expressing its moral support for HCT and proposing some key ethically acceptable standards.
The WHO believes that well-designed HCTs can not only accelerate the development of a COVID-19 vaccine, but also make the eventual widespread vaccine potentially more effective. (Well designed challenge studies might thus not only accelerate COVID-19 vaccine developmen, but also make it more likely that the vaccines ultimately deployed are more effective)
Along with the controversy, on February 17, 2021, Imperial College London officially released information on human trials of the new coronavirus, and openly recruited volunteers to actively infect the new coronavirus.
Source: Screenshot of UKcovidchallenge official website
According to the information in the preprinted paper, this world’s first COVID-19 human challenge trial research protocol has been approved by the British Health Research Agency’s ad hoc expert ethics committee, and written informed consent has been obtained from all volunteers.
The entire study was conducted by the trial steering committee. (TSC) and was advised by the Independent Data and Safety Monitoring Board (DSMB).
Next step: Delta human challenge trial may be conducted
The COVID-19 epidemic has been going on for more than two years. In the past two years, humans have had a number of COVID-19 vaccines, and have also experienced the variables brought by Delta and Omicron.
So, what significance does this COVID-19 human challenge test bring us to the current epidemic?
The trial’s researchers say the study’s success provides a strategy for testing the effectiveness of treatments, vaccines, and virus mutations, while also potentially helping scientists understand why some people’s immune defenses are overwhelmed by the new coronavirus, while others are not. Others won’t.
Commenting on criticism of the trial, study co-investigator Peter Openshaw, a respiratory physician and immunologist at ICL, said: “Is it ethical not to do these studies? unique insights.”
The researchers are planning their next steps, hoping to conduct a human challenge study using the standardized Delta strain in the spring.
“This is a very important piece of work,” said David Dowdy, an infectious disease epidemiologist at the Johns Hopkins School of Public Health. “No other study has been able to simultaneously track a case of known infection time. Symptoms and Immunology.”
Dr Andrew Catchpole, chief scientific officer of hVIVO, who participated in the trial, said: “This study provides valuable insights into the progression of Covid-19 infection in healthy young adults. Importantly, this study shows that the Covid-19 human challenge study is safe and that volunteers are resistant to Covid-19. Receptivity was good, no serious symptoms, and no serious adverse events.”
Some experts mentioned: The most important significance of the UK’s COVID-19 human challenge test is to prove that this test is safe and feasible. Currently, the third-phase clinical trials of the COVID-19 vaccine are carried out by tens of thousands of people.
The large sample of the vaccine requires at least several thousand people to participate, which will take several months and years to come. However, such a large sample is not needed at all for human challenge trials of vaccines, and it does not take a long time.
In 2016, the cholera vaccine Vaxchora approved by the US FDA was also developed using human challenge trials: 68 Vaxchora recipients and 66 placebo recipients were challenged by oral Vibrio cholerae. Vaxchora was 90 percent effective in people challenged 10 days after vaccination and 80 percent effective in people challenged 3 months after vaccination. After the results of the trial were announced, Vaxchora was successfully approved.
For the COVID-19 epidemic, even though we have a wide range of vaccines now, we are still very likely to face the challenge of new mutant strains in the future.
Even now, our understanding of the COVID-19 is still inconsistent and wrong, such as the length of the incubation period, how long it will be infectious after infection, the significance of rapid antigen testing, etc.
The COVID-19 epidemic is still not visible at present. At the end, new vaccines may also be needed, and the role of human challenges in the rapid development of vaccines should not be missed.
Killingley B, Mann A, Kalinova M, et al. Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge[J]. 2022.
34 people were actively infected with COVID-19: Test Results Announced!
(source:internet, reference only)