During a first-of-its-kind COVID-19 human-challenge trial, healthy young individuals who were purposely subjected to the coronavirus SARS-CoV-2 had minor symptoms, if any at all. This kind of trial offers a once-in-a-lifetime chance to research viral infections from beginning to end, but they are contentious due to the hazards they entail to patients. The study verifies findings from previous COVID-19 investigations.
According to researchers, the UK study of 34 people aged 18 to 30 years old demonstrates that these studies can be conducted adequately and provides the framework for more in-depth research of vaccines, antivirals, and immunological responses to SARS-CoV-2 infection. The findings were published on the preprint service Research Square on February 1st and have not yet been peer-reviewed, reports Nature.
Approximately half of those who received a small dosage of the virus did not become infected, while some of those who did were asymptomatic. Sore throats, runny noses, and a loss of smell and taste were among the mild-to-moderate symptoms experienced by those who had COVID-19.
“It presents a potentially important advance in how to assess future vaccine and drug efficacy,” Miles Davenport, an immunologist at Sydney’s University of New South Wales, agrees. “This opens a number of important possibilities to study immunity in a controlled environment.”
Some academics, nonetheless, doubt if the study’s findings are significant enough to warrant the dangers to subjects, including the possibility of long-term side effects. “In my mind, it’s still not entirely clear whether these studies are ethically justified, and I’m waiting to see what else they’ve found,” says Seema Shah, a bioethicist at Northwestern University in Chicago, Illinois.
Finding the dose
Over decades, human-challenge experiments are often used to research influenza, malaria, and a variety of other infectious diseases. Several experts advocated that such studies with SARS-CoV-2 should be conducted throughout the early months of the pandemic to speed up vaccine development. Others, on the other hand, considered challenging trials as too risky to be acceptable, especially given how little was understood about the virus and how few, if any, viable treatments were present.
The study was introduced in October 2020, and the very first volunteers were subjected to the virus in early 2021. It was headed by Imperial College London scientists and a Dublin-based commercial clinical-research business called Open Orphan and its London-based subsidiary hVIVO. Volunteers were compensated with £4,565 (US$6,200) for their time spent in a high-level seclusion unit at the Royal Free Hospital in London for at least two weeks.
The initial participants were given a really small dose of a virus strain that was circulating in the United Kingdom in early 2020, approximately similar to the quantity of virus in a solitary droplet of nasal fluid. According to Andrew Catchpole, chief scientific officer of hVIVO, scientists expected a greater dosage to infect the majority of volunteers. However, the initial dose infected upwards of half of the subjects.
Infected people’s bodies reproduced the virus at breakneck speed. People acquired their initial symptoms and tested positive using sensitive PCR testing, on average, just under two days following exposure. In comparison, real-world epidemiological investigations have recorded a five-day ‘incubation period’ between a possible exposure and symptoms. The virus remained at high levels for an average of 9 days and up to 12 days.
Sore throats, runny noses, and sneezing seemed to be the most common symptoms, which were similar to those of other respiratory diseases. Fever was less frequent, and no one got the chronic cough that had been associated with COVID-19, according to Catchpole. Approximately 70% of infected volunteers lost their perceptions of smell and taste to varying degrees – another COVID-19 hallmark. In five of the individuals, these issues continued for more than six months, and in one for more than nine months. Some individuals showed no signs at all, yet they had just as much virus in their upper airways as those who did, and their infections persisted just as much.
The study’s researchers are trying to figure out why so many participants were not affected despite becoming treated to SARS-CoV-2. According to Christopher Chiu, a physician-scientist at Imperial College London who conducted the study, certain uninfected patients had really low levels of virus for brief periods of time, indicating that their immune systems were actively battling the virus.
Future research on the challenge-trial participants will try to figure out why. Some people may be protected against COVID-19 by coronaviruses that cause the common cold, according to a previous study. One other theory is that certain individuals have powerful innate immune responses that do not necessitate prior exposure to a disease or a virus that is similarly related. “We’re trying to understand the fundamentals of why people are protected even though they’ve not been exposed to a virus like this before,” Chiu adds.
His group intends to conduct another challenge study in which vaccinated people would be exposed to the Delta version of SARS-CoV-2. The goal of this research is to find immunological components that shield individuals from ‘breakthrough’ infections following vaccination. Human-challenge trials for SARS-CoV-2 will most likely enlist only those at very low risk of severe sickness for the time being, according to Catchpole. However, if researchers acquire expertise conducting these challenge trials properly, Chiu believes it may be possible to broaden them to include at-risk populations such as the elderly.
According to Matthew Memoli, an infectious-disease specialist and virologist at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, the trial appeared to be safe and well-conducted.
He adds that it should let some people feel more at ease with doing future human-challenge trials for SARS-CoV-2. He added that such trials could aid in the development of vaccines that protect against a wide range of coronaviruses, not just SARS-CoV-2.
The study, according to Meagan Deming, a vaccine researcher and virologist at the University of Maryland in Baltimore, verifies findings from previous COVID-19 investigations, like the rapid spike in viral levels. However, it hasn’t quelled her fears about subjecting individuals to a SARS-CoV-2 strain that hasn’t even been attenuated. She observes that moreover, two-thirds of infected subjects had issues with smell or taste that lasted for more than six months in certain circumstances.
“It sounds like this is the most serious risk that materialized. This is the one to keep an eye on,” Shah adds. Furthermore, she worries if the study’s findings thus far warrant such costs. “This study reads like a promissory note that ultimately, in conjunction with the other research they’re doing, there will eventually be substantial scientific and social benefits. But we’re not really seeing that yet.”