Scientists Deliberately Gave People SARS-CoV-2
Although still controversial, human challenge studies which refer to trial’s participants are intentionally exposed to the pathogen that causes the examined infectious disease are not new. In fact, the first documented human challenge trial dates to 1700s which was conducted to evaluate the effectivity of variolation against smallpox. Over the 20th and 21 centuries, this approach was used to fast-track the vaccines for more than 15 major pathogens including cholera, typhoid, influenza, and malaria.
With the rise of the COVID-19 pandemic, some researchers have argued for conducting such studies with SARS-CoV-2 in the early onset of the pandemic to expediate the development of vaccines. Still, others asserted that these trials were extremely risky especially when we know so little about SARS-CoV-2 and lack efficient treatment.
In early 2021, U.K.-based researchers conducted a human challenge trial in which participants were deliberately exposed to minimal doses of SARS-CoV-2. Although the study has not yet been peer-reviewed, the team has shared early results from these experiments. Here’s what to know about the research and its early findings.
The Beginning of The Experiment
The study was led by researchers from Imperial College London, a Dublin based commercial clinical-research organization named Open Orphan, along with its London-based subsidiary hVIVO. It was announced in October 2020 and the experiments started in early 2021.
34 participants aged 18-30 were selected according to criteria defined by the protocol and examined for known risk factors such as co-morbidities, low or high body mass index, abnormal blood tests, spirometry, and chest radiography prior to the trials. Through sensitive antibody testing, the researchers also ensured that none of the participants had a prior infection with SARS-CoV-2 or were vaccinated against the virus. After the screening, the volunteers that fulfill the criteria received a very low dose of SARS-CoV-2, roughly the viral load in a single droplet of nasal fluid, via nose drops.
The Findings of The Trial
The early results of the trial have offered interesting insight on viral behavior and immune responses.
First, although the researcher anticipated that a higher dose of SARS-CoV-2 would be required, the initial dose has proved to be sufficient to infect a majority of the participants. After exposure to the virus, 18 of the 34 participants got infected. Some uninfected participants had very low viral loads for short periods of time indicating that their immune systems were actively fighting the virus. Within those who got infected, the virus replicated extremely rapidly. On average, people tested positive and developed their first symptoms 42 hours after their exposure to the virus. SARS-CoV-2 could be identified in the throat around 40 hours after exposure and in the nose, around 58 hours after exposure. These findings contrast significantly with those of real-world epidemiological studies which reported an approximately 5-day incubation period. On average, the participants’ viral loads reached peak five days after their exposure and high viral loads remained present for an average of 9 days up until 12 days.
16 of 18 participants who became infected developed mild to moderate symptoms that are typical of other respiratory syndromes such as sore throats, runny noses, sneezing, and to a lesser degree, fever. Although coughing has been specified as a common symptom of COVID-19 disease, no one developed persistent cough. Around 70% of the infected participants lost their sense of smell and/ or taste to various extents. These issues prevailed for more than 6 months in 5 participants and more than 9 months in one. Some of the infected participants were asymptomatic but they had viral loads similar to those who developed symptoms and their infections persisted as long.
Finally, the team has reported that lateral flow tests namely rapid antigen tests accurately detected the virus throughout the course of infection while being somewhat less sensitive at the very beginning and the end of the infection due to relatively lower viral loads. These findings support that lateral flow tests are reliable in detecting the presence of infectious levels of SARS-COV-2.
Why Do We Need Human Challenge Trials?
Several researchers argue that such experiments introduce us with the unique opportunity to examine infections comprehensively from the point of exposure to the removal of the virus from the body. As human challenge trials enable the examination of immunity and viral behavior in a controlled environment, they present many possibilities for more comprehensive and precise analyses of vaccines, drug efficacy and immune response.
So far, this UK-based research constitutes the only experiment that could monitor both the symptoms and the immune responses from a known point of infection. The team state that the findings are representative of COVID-19 regardless of the variant used in the experiment, and they could contribute to the development of vaccines that protect against a wide range of coronaviruses.
Is The Trial Ethically Justifiable?
Although the trials were reported to look safe and well-conducted, some researchers are not convinced as to whether these studies are ethically justified. Regardless of dosage, exposing people to a SARS-CoV-2 strain that has not been weakened generated concerned due to the risk it poses to the participants. Some researchers argue that due to the lack of certainty about the severity of infection the insights gained from the experiment does not suffice to justify the risk associated with the exposure to SARS-CoV-2. Others call attention to the risk of long-term side effects by pointing out to the fact that some infected participants had issues with smell or taste which lasted more than 6 months. Altogether, despite the unique opportunities the approach presents, there is no consensus as to whether it is ethically justified.
Future of Human Challenge Trials in COVID-19 Research
In the future, the team plans to conduct similar experiments that will expose vaccinated participants to the delta variant. Researchers assert that this next experiment will attempt to detect the immune factors facilitating protection against ‘breakthrough’ infections after vaccination.
Further research aims to explain why some people do not get infected by SARS-CoV-2 although they have never had a prior encounter with the virus. The trials may be efficient in testing existing theories such as the suggestion that some people may have protection against SARS-CoV-2 due to their encounter with coronaviruses that cause the common cold or due to their potent innate immune responses that do not require a prior infection with specific pathogens.
Human challenge trials are currently exclusively performed on individuals at very low risk of severe disease. However, as our knowledge on viral behavior, immune responses, vaccines, treatments, and safety measures advances, it might be possible to broaden the group to involve people at different risk groups.
Furthermore, the study tested the accuracy of the rapid antigen test on detection of SARS-CoV-2. The findings suggest that rapid antigen tests can accurately detect the SARS-CoV-2 between the time interval from early infection to lower loads similarly PCR tests.
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- Killingley, B. et al. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-1121993/v1 (2022).