Results of the first ethically approved trial in which humans were infected with COVID-19

Part of Figure 1a of Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults by Killingley and coworkers, Nature Medicine, March 2022

The results of the first, or at least one of the first, studies where volunteers are deliberately infected with COVID-19, have just been published. In an interesting and important paper by Killingley et al. Thirty-four volunteers were exposed to a dose of COVID-19*. As a result half of them became infected, and of these 18, 16 showed symptoms at at least one time during the infection, while 2 (11% of those infected) never showed any symptoms. One of the big advantages of studies like this, is that you know exactly when the person was exposed to virus, and can track them from that time onwards. If someone is infected in the community, you usually don’t know when they were infected, and even if you do, then you don’t know at the time, so there is a delay in studying them.

Killingley and coworkers exploited this advantage, to get some really useful data, some of which is above. It shows two measures (red and blue curves) of the concentration of the virus SARS-CoV-2, found in samples taken from the nose of the volunteers exposed to the virus. It shows the time course of the COVID-19 infection in detail.

The viral load starts off zero, and typically first becomes measurable a couple of days after exposure. Note that the y-axis is a log scale, between days two and about seven, the amount of virus increases by about a factor of ten each day. Then between days seven and say twelve it decreases, but a bit more slowly that it rose. Finally, for another five days the viral load is low but only decreases slowly. The authors found that symptoms developed two to four days after exposure.

So, this plots supports self-isolation for ten days**. If you first noticed the infection by its symptoms, that will have been around three days after exposure. As you can see from above, the viral load will then typically be appreciable for another eight to ten days. If you were in that unfortunate position during the pandemic, I hope the above plot makes you feel a bit better about being confined to home for ten long days. It looks like that is about the right length of time.

I was also struck by a couple of other things in the paper. The first is:

Results from lateral flow tests were strongly associated with viable virus, and modeling showed that twice-weekly rapid antigen tests could diagnose infection before 70–80% of viable virus had been generated.

From Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults by Killingley and coworkers, Nature Medicine, March 2022

In other words, lateral flow tests work, and can pick up infections early on, when symptoms may be weak or entirely absent. They found that the two individuals who never developed symptoms had just as much virus in them, as those that did develop symptoms. Again this is consistent with individuals with no symptoms spreading the virus without know they are infected. Another argument for the use of lateral flow tests.

Today the UK government has dramatically scaled back free lateral flow tests. The day after Killingley et al.‘s paper made the case for these tests even stronger. Sigh.

The second thing that struck me about this important paper, is how elaborate was the ethical approval process the authors had to go through, and how scrupulous was the supervision of the study. All to protect the 34 young, healthy volunteers, that they deliberately exposed to COVID-19. This ethics process is normal. Any time any research is done involving people, ethical approval is required in advance of the research. The researchers must say carefully what they will do, so that any potential harms to the people can be assessed, and balanced against any benefits the research will produce.

This ethical-approval process exists to protect the brave volunteers, and it is impressive. It is good that in the past our Parliament has passed laws meaning that any trial that exposes the trial volunteers to a potentially harmful virus, has to be so carefully justified. What is less impressive is that the current government seems to be experimenting to see how many of the UK’s 60 million citizens can be exposed to COVID-19, and they don’t need to ask ethical approval from anyone. And the Parliament we elected in 2019 seems relaxed about the ethics of this.

* It is worth noting that they were infected by dropping virus into the nose, which is different to inhaling airborne virus – which is likely how most become infected naturally. This may affect the course of the infection.

** Note that plot up top is an average, there is considerable variety between one infected person and another.

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