Tuesday, Feb. 23, 2021

In the news this week: Human trials of COVID-19 infection will soon begin in the UK with a group of 90 volunteers. We have seen discussion of this idea for almost a year, but the green light came last week when a company named Open Orphan announced the approval of an independent Research Ethics Committee on Feb. 17 which allows the project to go forward under its subsidiary hVIVO. Meanwhile, a nonprofit organization called 1 Day Sooner (https://www.1daysooner.org/) has been advocating since April specifically for people who want to take part in COVID-19 human challenge trials. They claim to have 38,659 volunteers from 166 countries.

Modern human challenge trials have come a long way since the volunteer infection trials I’m most familiar with: Walter Reed’s tests on transmission of yellow fever during the construction of the Panama Canal over 100 years ago. Those trials included having mosquitos feed on people who had yellow fever and then on healthy volunteers to see if the volunteers got yellow fever. They did. In another trial healthy volunteers spent a few days in a cabin furnished with bedding from yellow fever victims but protected from mosquitos. These volunteers stayed healthy. Eliminating mosquitos was the key to completing the canal.

I had no idea that human trials are still going on all the time, other than the well-publicized phase three vaccine clinical trials we’ve all heard about. What can small-scale COVID human challenge trials tell us? Who volunteers? Why? If you want a little more information than you can get in the average news story, I recommend going to the websites of these three organizations. Here’s a sampling of what I found out.

  • Open Orphan is a contract research organization (CRO) which provides services to pharmaceutical companies in the area of human challenge trials testing vaccines and antivirals (https://www.openorphan.com/about-us/company-overview). I liked their Media Coverage page which had links to stories about human trials, such as “‘If I get seriously ill, it’s worth it’: volunteers to be infected with coronavirus in world first human trials,” (see link below) about an 18-year-old student taking his gap year to be one of the 90 volunteers for COVID trials. He believes the benefits outweigh the risks, but admits his parents aren’t enthusiastic about his decision.
  • hVIVO, a subsidiary of Open Orphan, specializes in viral challenge studies in influenza, respiratory syncytial virus, asthma, COPD and more to help develop treatments and vaccines. They have their own virology and immunology laboraties. They even have a clinical trial program called FluCamp (https://hvivo.com/volunteers/) — UK residents only, please.
  • 1 Day Sooner is a nonprofit organization which advocates for challenge trial volunteers. Their site deals with questions like volunteer rights, transparency, ethics, compensation, and informed consent. One FAQ that I want to revisit in a later column summarizes what is known about Long-Term Effects of COVID-19 (https://www.1daysooner.org/long-term-risks-faq), certainly something a volunteer for a COVID study would want to know. Check out the “Volunteer Ambassadors” page (https://www.1daysooner.org/team#ambassadors) to see some human challenge volunteers. They also provide a summary of “Objections to COVID-19 Human Challenge Trials” (https://www.1daysooner.org/objections-to-challenge-trials) with six common objections and replies to each.

But the three site above are not the place to go if you really want to understand the objections to human challenge trials with COVID. Here are a few well-thought-out opinion pieces by experts who question the ethical justification to tests that deliberately infect healthy people with coronavirus. (links below)

A quick summary of objections: The trials involve infecting young healthy people with a disease which has no cure and which has potential for long-term harm, including cognitive damage, strokes, and damage to the heart and lungs. The information from studies with this select volunteer group may not apply to those people most at risk from COVID. Previous challenge studies have involved influenza and RSV (respiratory syncytial virus) which are much better understood than COVID-19. All true. Note that these articles are opposed to human challenge trials with COVID, not volunteer trials in general or vaccine clinical trials.

What is it that the upcoming human challenge trials propose to do?

The participants in the upcoming trials in the UK will consist of 90 healthy volunteers aged 18-30 years who have never had a COVID infection. They will receive a minimum known dose of virus into their nose and stay quarantined in a hospital for 14 days under constant medical supervision. After discharge, they will have follow-up testing for a year. They will receive compensation for their time. Possibly we can understand the course of the disease much better and even learn how to prevent it if we can closely observe the course it takes after a known and quantifiable exposure.

What can be learned from this kind of study? I’ve seen the following suggested:

  1. How much virus does it take to start an infection? In fact, the first objective will test what the minimum amount actually is.
  2. How does an infected person transmit the virus to others?
  3. What factors affect how and whether the virus is transmitted?
  4. How does the immune system react to this virus?
  5. How long does immunity last after a person has been infected or vaccinated?
  6. Do vaccines prevent transmission of COVID-19?
  7. Why do some people have symptoms and others do not?

Later studies might be used to determine which second-generation vaccines are the most effective, especially with new variants that evolve as the virus continues to spread. Human challenge studies would provide this information much faster than conventional vaccine clinical trials which rely on a certain number of people (some injected with vaccine, others with a placebo) to become infected (or not) while living their normal lives.

The volunteers give moving accounts of their experiences. Some have even been in viral studies before. They sound intelligent and highly motivated. Still, with so little known at this point, it is hard to see exactly what constitutes informed consent. An element of the unknown comes with the territory, I expect. What do you think?

Today’s Notable Headlines

“The U.K. approved the world’s first COVID-19 human challenge trial,” Science News, Feb. 18, 2021. https://www.sciencenews.org/article/coronavirus-uk-first-human-challenge-trial-covid-19

“‘If I get seriously ill, it’s worth it’: volunteers to be infected with coronavirus in world first human trials,” Independent, Feb. 18, 2021. https://www.independent.co.uk/news/uk/home-news/coronavirus-human-challenge-trials-covid-b1803781.html

“County Durham resident to be deliberately infected with Covid in UK trials,” The Northern Echo, Feb. 16, 2021. https://www.thenorthernecho.co.uk/news/19094304.county-durham-resident-deliberately-infected-covid-uk-trials/

“What are human challenge studies?” Medical News Today, Feb. 22, 2021. https://www.medicalnewstoday.com/articles/what-are-human-challenge-studies?utm_source=Sailthru%20Email&utm_medium=Email&utm_campaign=newsAlerts&utm_term=coronavirus&utm_content=2021-02-22&apid=36911271&rvid=fa7c2c38d4d1e41b83e8016b052dc63c6d6ff4a940cbaa533edc93e1a81aab24

“UK will soon expose volunteers to Covid in world’s first ‘human challenge’ study,” CNBC, Feb. 17, 2021. https://www.cnbc.com/2021/02/17/uk-to-expose-volunteers-to-covid-in-world-first-human-challenge-study.html

“Volunteers sign up to put their lives on the line for a coronavirus vaccine,” Washington Post, June 15, 2020. https://www.washingtonpost.com/health/2020/06/15/volunteers-sign-up-put-their-lives-line-coronavirus-vaccine/

Opposed to Human Challenge Studies with COVID:

“Covid-19 vaccines: Should we allow human challenge studies to infect healthy volunteers with SARS-CoV-2?” theBMJ, Nov. 9, 2020. https://www.bmj.com/content/371/bmj.m4258

“Why federal government should reject human challenge trials for COVID-19 vaccine,” CBC News Canada, Nov. 17, 2020. https://www.cbc.ca/news/opinion/opinion-covid-vaccine-human-challenge-trials-1.5790713

“Opinion: For now, it’s unethical to use human challenge studies for SARS-CoV-2 vaccine development,” PNAS, pub. Oct. 29, 2020; updated Nov. 17, 2021.https://www.pnas.org/content/117/46/28538

Additional Sources:

Press release: “World’s first coronavirus Human Challenge study receives ethics approval in the UK,” Gov.uk, Feb 17, 2021. https://www.gov.uk/government/news/worlds-first-coronavirus-human-challenge-study-receives-ethics-approval-in-the-uk

Press release: “Ethics approval – COVID-19 Human Challenge Study,” Open Orphan PLC, Feb. 17, 2021. https://otp.tools.investis.com/clients/uk/open_orphan/rns/regulatory-story.aspx?cid=2484&newsid=1453479

The Human Challenge Programme, hVIVO. https://hvivo.com/the-human-challenge-programme/

Why am I doing this?

The coronavirus pandemic will be indelibly written on our memories just as the Great Depression or the Battle of Britain left their mark on past generations. I intend to journal the pandemic experience from three perspectives: as a retired medical technologist, as a historian (Ph.D., 2014), and an ordinary person living through an extraordinary world crisis.

You are on History’s Edge.

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