Thomas had a mild case – just a fever. So now she’s volunteering to help researchers understand the aftermath of infection, waiting to hear whether she’ll get into the clinical trial. In the meantime, she’s an organizer for for 1daysooner, a non-profit advocacy group for people wishing to participate in research and launched in April 2020. A major focus has been joining clinical trials for COVID vaccines.
Why would anyone sign up for a second encounter with the virus that has shattered the world?
“My #1 reason is the fact that coronavirus has had such a horrible impact and this is a really easy and tangible way to do a lot of good. How often can you say that? Being in the trial to be reinfected would be an honor,” Thomas told Genetic Literacy Project.
Her second reason for seeking entry into the reinfection trial is “wanting to learn as much about the disease as possible so we can avoid ever having to do this again. I’ve been in Europe the whole time, except about a month in the States, and it’s been hard. European countries have responded more strictly to coronavirus and honestly it’s been really difficult for me and my friends, financially, mentally, and emotionally. Lockdown was necessary, but I never want to see it happen again.”
One challenge trial underway, another about to begin
The UK is the only nation currently conducting “challenge studies,” which intentionally infect volunteers and then track them carefully to see what happens. A trial underway is for people who’ve never been infected, and a trial about to start is for those who have already had COVID – none of the participants in either trial have been vaccinated.
The first trial started at Imperial College London, Royal Free Hospital in March, in early March and is funded by the National Health Service. Healthy volunteers aged 18 to 30 had tiny amounts of virus dripped into their noses. The people were then carefully monitored.
On March 25, the media covered the first 3 volunteers released from their two-week quarantine, all healthy. Future groups, 250 people in total, will receive increases in viral dose. Their responses, the investigators hope, will reveal the lowest viral dose associated with symptoms and replication in the nose.
A challenge trial yields more information, faster, than a more traditional trial design in which volunteers are exposed to the pathogen in a natural setting. COVID vaccine trials to date, for example, have compared large groups of vaccinated and unvaccinated people (given placebo) when they return to their communities and encounter SARS-CoV-2.
Challenge studies have been done before, such as to improve a vaccine against cholera, tested in Baltimore. But suggestions of conducting challenge studies for COVID were initially met with much resistance because so much is still unknown about the infectious disease.
If the findings on healthy unvaccinated volunteers intentionally exposed to SARS-CoV-2 prove useful, then a challenge component may be incorporated into future clinical trials for COVID vaccines. Said Andrew Catchpole, Chief Scientific Officer at hVIVO, the organization that is signing up potential participants for the Imperial College study (as well as for the second study that Thomas has applied for) “We expect that this study will greatly assist our understanding of this disease and provide insights into its progression, natural immune response, and transmission. We look forward to publishing the study’s results in due course and moving forward with vaccine challenge studies later this year.”
The second trial will kick off in May, sponsored by Wellcome Trust and conducted at hospitals affiliated with the University of Oxford. Plans are to enroll up to 64 people aged 18 to 30. Phase 1 will examine lowest-dose-to-reinfect and phase 2 will document immune responses. Findings about the timing of reinfection and the immune response can perhaps then be factored into decisions about re-openings and leaving our COVID pods and bubbles for more normal social behavior.
People can register their interest in participating in either trial at ukcovidchallenge.com, the website for hVIVO, which has led similar studies for other infectious diseases.
Thomas finds the common response of horror at the idea of intentionally infecting anyone “infuriating.” “We take risks every day just crossing the street. Getting coronavirus is a risk, sure, but it’s a lot less risky than going to war or donating a kidney, and we let people do that. And I think it would be a very small risk for me, because I got coronavirus and I was alright.”
She adds that had challenge trials been part of the developmental trajectory for the vaccines already available, approvals might have come sooner, blunting some of the pain and suffering of the lockdowns she’s lived through.
A long history
Challenge studies for COVID-19 join a long list of past similar efforts. The strategy has helped to quell epidemics of flu, malaria, cholera, dengue, shigella, typhoid fever, giardia, tuberculosis, rhinovirus, and norovirus. Challenge studies were slated for Zika virus infection but that disease abated on its own. But challenge studies sped approval of an Ebola vaccine in 2019, accomplished in a mere 10 months.
But challenge studies have a dark side to their history too. Doctors in Nazi Germany did it, of course without consent. And an influenza vaccine was tested on prisoners and intellectually disabled children in a state facility in Pennsylvania. Even revered polio vaccine inventor Jonas Salk tested flu vaccine on mental patients and prisoners in Michigan.
Participants in the two challenge studies for COVID follow a detailed informed consent process. Genetic Literacy Project covered the bioethics, regulatory process for COVID-19 challenge studies, and the World Health Organization’s “roadmap,” as well as the details of the trial protocols in September 2020 here.
Because challenge trials for COVID are just getting underway, to make ultimate analyses more transparent, Josh Morrison, executive director of 1Day Sooner, and Charles Weijer, a bioethicist at Western University in London, Canada, call for publication of full trial protocols, in an opinion piece at the British Medical Journal blog.
Certainly more than a few hundred people in challenge trials will need to be followed to fill in the blanks about reinfection. Once treatments for COVID improve, perhaps challenge studies will find a way to ethically include volunteers who have risk factors – the current two trials are enrolling young, healthy people.
Then public health experts will need to translate what’s been learned from the challenge studies about the timing and sustainability of natural immunity against COVID-19 into policy – and hope for compliance.
It’s jarring to consider the utter selflessness of people who volunteer for challenge studies against the larger and louder backdrop of people burning masks and crowding shorelines in the name of preserving their perceived personal freedoms.
In this second year of the pandemic, as variants battle vaccines, perhaps volunteers who have already been infected, or vaccinated, can guide the days ahead as we recover. I hope Lauren Thomas gets into the trial!
Ricki Lewis has a PhD in genetics and is a science writer and author of several human genetics books. She is an adjunct professor for the Alden March Bioethics Institute at Albany Medical College. Follow her at her website or Twitter @rickilewis