The Japan Times

Volunteers chose to get COVID-19 in the name of science

‘Challenge’ trials have allowed researcher­s to examine various attributes of the virus

- FAYE FLAM

Jacob Hopkins, 24, tried hard not to get COVID-19 in the months leading up to March 2021, when, if he succeeded, he could be part of a unique experiment in which he was deliberate­ly infected with the virus.

Almost a year earlier, he had put his name on a list of volunteers. Months went by until, on Dec. 23, he finally heard back from someone associated with the experiment. He ended up being the very first volunteer given the infection — patient 1.

As he described it to me, he took a cab to a hospital in London, wearing a mask so he would be sure not to catch COVID-19 at the last minute. He arrived on a Friday, went through a battery of tests over two days, and on Monday, five health care workers came in wearing full PPE, like something out of the movie “Contagion,” pulling in a tank of solution containing SARS-CoV-2.

They had him lie at the edge of the bed with his head back and squirted the infectious solution up his nose. He was one of 34 volunteers.

This kind of experiment is called a “challenge” trial. Thanks to Hopkins and the other volunteers, researcher­s learned some fascinatin­g details about viral loads, symptoms and incubation times. A paper on the findings was published in Nature on March 31 of this year.

I’d written about challenge trials in May 2020 and was so compelled by the idea that I put my name on a list of volunteers that scientists could call on if they organized such a trial. I thought I was a good candidate because I had no conditions that would make me unusually vulnerable to COVID19. Because of the nature of my work, I could call on the world’s top experts to advise me about safety and scientific value of any trial I might enter.

At the time, nobody knew how long it would take to get vaccines tested and approved. Challenge trials have been used to study malaria and influenza and looked like a possible shortcut to speed up arrival of a COVID-19 vaccine. For me, the experience would have led to a series of great stories. Journalist­s do far more dangerous things for work.

But events took a surprising turn. Standard vaccine trials progressed with record speed and the first vaccine candidates looked impressive­ly effective. By the end of 2020, vaccines were already being offered to health care workers in some places. I’d assumed any challenge trials would have been called off.

But the challenge trial Hopkins took part in did go forward. “We started with the lowest dose we can reliably produce,” said Christophe­r Chiu, a researcher at Imperial College London, who headed the experiment. If nobody got infected they’d step up the dose, slightly, he said, but on the first try, they got slightly past 50% — infecting 18 of 34 volunteers.

Chiu said they are only beginning to learn from the data they’ve accumulate­d. Two of the 18 infected had no symptoms at all, and the rest had mild or moderate symptoms — mostly sore throats and runny noses.

One of the first big surprises was how short the incubation period was, Chiu told me. It was only two days before the volunteers who got infected tested positive on PCR tests and not much longer to register a positive on rapid tests. Those who got symptoms noticed them between two and four days after exposure.

Another surprise was that the amount of virus people produced didn’t reflect the severity of their symptoms — those who produced a lot of virus sometimes had very mild or no symptoms and those who felt sicker sometimes produced less.

Since the date of exposure was known, the data were also useful for examining testing efficacy. While rapid tests didn’t always pick up the infection as early as the more sensitive PCR test, Chiu said it appeared to pick up most infections around the time that would likely coincide with peak transmissi­bility.

Chiu said everyone recovered quickly from all the symptoms except for changes in taste and smell. Those lasted for around six months in five of the volunteers, and one was still reporting a diminished sense of smell nine months after exposure.

Since this experiment took place, there’s been big increase in the awareness of the risk of lingering or even permanent symptoms and several studies have hinted at the possibilit­y of long-term changes in the heart and brain, though scientists are still trying to figure out if the subtle changes have real health significan­ce.

Hopkins, who works for the charity group Citizens’ Advice, said he was well aware of the risk of long COVID-19, but thinks it was outweighed by the benefit of being part of the fight against the pandemic. He feels that the researcher­s fully informed him of the risks of infection and what would be involved in the experiment. He told me he is a risk-taker by nature and recently went skydiving in Dubai. “I love adrenaline,” he said. And he’s deeply interested in medical research and has donated stem cells to people with blood cancers.

The course of his illness was brief. He was infected on a Monday, tested positive on Wednesday and started feeling chills on Thursday. He said he had flulike symptoms that were “pretty rough” but lasted only two days. Then, a few days after feeling better, while still in isolation and undergoing tests, he failed a smell test. Odors on the test that had been strong before his infection smelled like absolutely nothing. Then a few days later, his sense of smell returned.

Challenge trials give scientists a uniquely controlled data set, helping them gauge things like incubation time, accuracy of tests and long-term consequenc­es of infection. They may reveal something about why some people get sick and others don’t. It’s the kind of controlled, experiment­al data that’s been so badly lacking in a pandemic that’s been ruled by educated guesses announced with inappropri­ate certainty.

The situation has changed a lot since this experiment was done. We’re contending with descendant­s of omicron — BA.2, BA.2.121, BA.4 and BA.5, and almost everyone in the U.K. and the U.S. has some degree of immunity to some version of the virus. But the challenge trial data could neverthele­ss be extremely useful right now.

Those data suggest that people who test positive may remain infectious far longer than the five days they’re supposed to quarantine. And for those potentiall­y exposed, the data could be turned into better informatio­n on when to use home or PCR tests and how much people can rely on the results. The challenge trial results also open up new scientific questions, including why some people resist getting infected at all — even when the virus is sprayed directly up their noses.

Faye Flam is a Bloomberg Opinion columnist and host of the podcast ‘Follow the Science.

 ?? REUTERS ?? The “challenge” trial provided an insight into how short the COVID-19 incubation period actually is.
REUTERS The “challenge” trial provided an insight into how short the COVID-19 incubation period actually is.

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