Why UK doctors are deliberately infecting people with SARS-CoV-2
Doctors in the UK are about to deliberately infect dozens of people with SARS-CoV-2.
At first glance, you could be forgiven for asking why given that the nation is not short of patients with the virus.
But it’s part of a so-called 'human challenge trial' at the Royal Free Hospital in London, the world’s first such trial when it comes to investigating the remaining mysteries of SARS-CoV-2.
It is creating a stir within the international scientific community, with the hope that it will shed light on what happens to the human body during the very early stages of infection and show in greater detail how it responds before symptoms arise.
The researchers have said safety will be their top priority and are stressing that only healthy adults at low risk of disease will be recruited.
But doctors running these types of experiments do face ethical dilemmas, primarily because deliberate infection of healthy subjects breaches the 'do no harm' principle enshrined in the Hippocratic oath.
Previously, they have been used to understand the transmission and severity of bacterial and viral diseases including cholera, yellow fever and malaria, as well as influenza and tetanus.
Read more: Vax trial to infect volunteers with COVID-19
In 1901, for instance, US Army physician Major Walter Reed was able to confirm that yellow fever transmitted by particular species of mosquito rather than by direct contact between infected patients.
This was done by allowing mosquitoes to bite infected patients before transferring the insect to bite the healthy volunteers.
Today, the purpose of these trials is usually to bypass lengthy phase 2 and 3 clinical trials, fast-tracking the development of vaccines and treatments when time is of the essence.
The UK trial involves up to 90 healthy volunteers aged 18-30 years.
“A couple of days after they arrive, assuming all [the screening] tests are fine, they will receive the virus as drops in the nose … and lie flat on their back for half an hour” says chief investigator Dr Chris Chiu, an infectious diseases specialist at Imperial College London.
His team will use a medical-grade version of the original SARS-CoV-2 variant that's been circulating in the UK since the start of the pandemic.
Once infected, participants will quarantine for 14 days under constant medical supervision in hospital rooms akin to hermetically sealed vaults.
There will be strict protocols to prevent leaks. All the ventilated air leaving the facility will be treated, waste will be subject to careful decontamination, and a dedicated lab is being set up to test daily blood samples and nose swabs.
As a precaution against severe illness, the volunteers will be given the antiviral medication remdesivir as soon as they start shedding the virus from their nose.
For their troubles they will be compensated around £4500 (approximately AUD$8000) and followed up for a year to monitor any long-lasting symptoms or complications.
The initial aim of the research is to determine the smallest amount of SARS-CoV-2 needed to cause infection and subsequent illness.
Scientists will also analyse how the coronavirus grows in the nasal passage, where there is a high concentration of the ACE2 receptors used by the virus to enter cells.
Another aspect of the study is to identify the type of immune response that needs to be triggered against the virus.
The data collected could accelerate vaccine development, according to virologist Professor Lawrence Young from the University of Warwick, who is not involved in the study.
“It will also help us to better determine the activity of various vaccine candidates and to possibly investigate differences in response to infection with virus variants.”
But there are vexed ethical issues.
According to WHO guidelines published four years ago, in many cases human challenge with a virulent or even an attenuated organism “would not be considered ethical or safe”.
This caution is no doubt born of medicine’s darker history where patient rights have often been secondary to the quest for knowledge.
At the very birth of vaccine development, Dr Edward Jenner conducted a human challenge experiment by intentionally exposing his gardener’s eight-year-old son to cowpox, a milder form of smallpox.
Although the child only developed a fever and recovered, the father of immunology was essentially flying blind as he had no proven treatment at hand in case the boy fell seriously ill.
Fast-forward to the World War II, Nazi Germany and Japan experimented on thousands of prisoners and victims of their respective regimes, by infecting them with anthrax, cholera, typhoid fever and dysentery.
It was these war crimes that led in part to the Nuremberg Code in 1947 and, a year later, the Declaration of Geneva, a revised version of the Hippocratic Oath.
With COVID-19 there are obvious risks which probably explains why UK study is the first human challenge study in the world involving SARS-CoV-2 to receive ethics approval.
The first is simply that current COVID-19 treatment options are also limited.
Dr Stephen Griffin from the University of Leeds said: “While we do know of treatments such as dexamethasone and tocilizumab help some patients with severe disease, we do not have a treatment that guarantees recovery in everyone.
“Whilst we understand a great deal about the risk factors associated with severe COVID-19, it is not always clear why certain patients progress whilst others do not.”
The second issue is that the clinical experiences of the last 12 months show that those even with mild infections can still experience long-term morbidity, regardless of their age or risk category.
For instance last year Australian Doctor spoke with a 50-year-old Sydney GP who was diagnosed with COVID-19 was subsequently left with new-onset epilepsy and myocarditis.
This doctor was an avid cyclist and in perfect health before the coronavirus infection.
It has been estimated that one in 10 patients will have symptoms that last longer than 12 weeks — a condition that has now been labelled 'long COVID', or post-acute COVID-19.
Last year, Professor Joerg Hasford, an epidemiologist and president of the Association of Medical Ethics Committees in Germany, warned of the dangers of human challenge trials in the rush for effective vaccines.
“The relevance of the ethical issues with COVID-19 challenge trials could be reduced if a highly effective and safe treatment is available,” he acknowledged in a letter to the BMJ last October.
“It may be questionable, however, that a person can imagine the consequences for his quality of life when a scarred lung tissue, for instance, impairs his health many years later.
“In addition, it is a misunderstanding of the commitment of informed consent that it permits medically inappropriate behaviour.
“Thus, it may happen that a physician involved in a COVID-19 challenge trial gets prosecuted, convicted and may end in prison or may lose the license, if the patient suffers a severe adverse outcome.”
He added: “Human beings should not become just a means to an end”.
More information: UK government announcement on COVID-19 human challenge trial