Vaccine Hunt: Is Injecting Human Volunteers With COVID-19 Ethical?

In the race to find a vaccine for COVID-19, an ethical debate is brewing over whether it’s justifiable to deliberately infect healthy volunteers with the disease in the hopes of achieving a scientific breakthrough sooner, according to the South China Morning Post.

And while consenting adults should be allowed to take whatever risks they want, there’s a known unknown regarding this relatively new illness – namely, why do most people who contract coronavirus range from asymptomatic to ‘worst flu of my life,’ only to fully recover, while others – known as ‘long haulers‘ – remain ill for months, experiencing ‘waves’ of debilitating symptoms with no end in sight.

We don’t know much about long haulers – particularly one’s chances of becoming one if infected with COVID-19.

Deliberately infecting people for research is done through what’s known as a “human challenge trial” (HCT) – which can be done concurrently with phase III vaccine trials. Deciding on HCTs for COVID-19 will be a panel of experts at the World Health Organization (WHO) – which includes Wuhan ‘Bat Woman’ Shi Zhengli, whose lab has fallen under suspicion as the source of the COVID-19 outbreak despite her repeated denials.

The advisory panel must contend with three ‘particularly contentious’ questions, according to SCMP:

• Second, the most probable HCT trial would recruit young, healthy volunteers to minimise the chance that they might die or become seriously ill after infection. But studies have found that elderly people, the group most vulnerable to the disease, are less responsive to vaccines. So, would it be worth the potential risks to find a vaccine that may not work for those who need it most?

• Third, would human challenge trials shorten the time to discover a vaccine? Would scientists gain any distinct advantage by exposing volunteers to the risks?

The experts in the WHO advisory group were split on the first and third questions, while the majority thought elderly people might not benefit from the findings of the trials. How Shi voted on these questions was not known. She did not reply to an email query from the South China Morning Post. –SCMP

In 2016, an ethics committee denied a proposal to use HCTs on a Zika virus vaccine over concerns of the risks it posed to volunteers and their sexual partners.

“The right question is whether challenge trials would increase study participants’ likelihood of similar bad outcomes, compared to two alternative scenarios: non-participation in any trial and participation in standard efficacy trials for the same vaccines,” posed Nir Eyal, a biomedical ethicist at Rutgers Global Health Institute.

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At present, a total of 32,665 people from 140 countries have signed up as volunteers for a potential HCT organized by volunteer group 1Day Sooner.

“We see considerable potential in the use of human challenge studies to accelerate Covid-19 vaccine development, [to help filter] and validate the best candidate vaccines, and optimise vaccination approaches,” said Professor Adrian Hill, director of Oxford University’s Jenner Institute – who is collaborating with 1Day Sooner to prepare for possible HCTs in addition to phase III clinical trials.

“We’re hoping to be doing challenge trials by the end of the year,” Hill told The Guardian. “This might be in parallel or might be after the phase-three trial is completed. They’re not competing options, they’re complementary.“

Abie Rohrig, a spokesman for 1Day Sooner, said no volunteers had asked to withdraw, despite some new findings pointing to possible long-term damage to organs such as the kidneys, heart and nerves, although they were rare among young adults.

“I have not heard from any volunteers about withdrawing because of these risks. Every volunteer I have personally spoken with understands that there is a large degree of uncertainty with respect to Covid-19, and they are willing to take on that uncertain risk in a challenge trial,” Rohrig said. -SCMP

Meanwhile, over 150 scientists and academics, including 15 Nobel laureates, have signed an open letter to the Director of the US National Institutes of Health, Francis Collins, asking the US government to collaborate with international teams to prepare for HCTs. That said, they also called for a ‘high-quality ethical review’ before they could start, according to the report.

“HCTs for Covid-19 have a tremendous amount of advocacy behind them that is unprecedented, for two main reasons. First, the advocacy group 1Day Sooner has been working hard to keep media attention focused on HCTs. Second, the widespread damage that has already been done by Covid-19 leaves the public grasping for any way to speed up vaccine development,” said Northwestern University bioethicist, Seema Shah – the primary author of the Zika ethics panel report.

Some scientists, however, have voiced serious concerns over whether the risks to volunteers is justified.

In an opinion piece published on the US medical website STAT, Michael Rosenblatt, chief medical officer of Flagship Pioneering and former chief medical officer of pharmaceutical giant Merck, wrote: “These authors, like 1Day Sooner’s volunteers, are well-intentioned but wrong.”

Rosenblatt, who is also an adviser to Moderna, said HCTs took months to prepare and Covid-19 vaccine development would not be accelerated by testing young volunteers.

“The volunteers might end up having risked their own health without truly helping those who are in greatest need of vaccine protection,” he said, referring to the elderly.

“An equally disturbing scenario is what if one of the first volunteers dies, either due to the play of chance, a problem with the vaccine, or the individual’s genetic make-up? This is unlikely to happen, but it can, and did, in another setting with consequences that stretched far beyond the single tragic death,” he wrote. He was referring to the death of an 18-year-old volunteer in the first gene therapy trials in 1999. The death put similar research on hold for years. -SCMP

What’s more, since no ‘weakened’ SARS-CoV-2 strains have been manufactured for use in HCTs, volunteers would be injected with ‘wild strains.’

“If HCTs are green-lighted now, when there is substantial uncertainty about the risks, they could set a new precedent for the level of risk and uncertainty that is tolerated in research,” said Shah. “If there are bad outcomes in these trials, or if the vaccines tested in them have safety issues when given to the general public, HCTs could hurt public trust in vaccines in the longer term.”