What are the risks to volunteers in a COVID-19 human challenge study?

Click to view 1Day Sooner's interactive risk model

Link to paper in risk analysis on COVID-19 challenge trial risks

1Day Sooner’s model estimates the risk of death and hospitalization for potential participants in a COVID-19 human challenge trial. Our key finding is that the mortality risk for a healthy challenge trial volunteer aged 20-29— around 1 in 10,000— is half the mortality risk of liposuction, a third of living kidney donation, and five hundred times lower than venturing into space as an astronaut. Users can adjust the expected risks based on the ages of participants, their gender, their pre-existing health level, and number of participants in a COVID-19 challenge trial. Analogous risks are displayed at the top of the model.

Note that this model is appropriate for considering a characterization study, in which volunteers are exposed to the coronavirus without first receiving a vaccine to determine the lowest dose capable of provoking infection. While the size of such a trial may vary, one approach would be to expose 5 volunteers each to 3 increasing titers of COVID-19, stopping if the majority or all volunteers for a given exposure level develop clinical disease. Following this, an additional 10-20 volunteers would be given the appropriate titer of COVID-19, to validate the initial result.

Our model does not analyze the long-term risks of COVID-19, which can be significant even for the young, healthy people. Our research team has put together a summary and FAQ of the most recent available data on the long-term risks of COVID-19.

Risk Model FAQs

What is the risk of death and hospitalization for a young, healthy human challenge trial volunteer?

Our model estimates that the risk of death for someone aged 20-29 with no comorbidities who is infected with COVID-19 is about 1 in 10,000. For context, that risk is twice as low as liposuction, three times lower than living kidney donation, and five hundred times lower than venturing into space as an astronaut. The risk for actual participants in a human challenge trial is likely to be even lower, due to enhanced screening, medical monitoring, and care.

What does “adjust for comorbidities” mean?

Several studies distinguish between the COVID-19 fatality rate for people with and without comorbidities. In our model, adjusting for comorbidities means assuming that a challenge trial will exclusively include participants without comorbidities to minimize risk.

What does “adjust for population heterogeneity” mean?

Different populations have different characteristics, which lead to different levels of risk. One output of the meta-analysis is an estimate of the risk within the population which has the lowest risk. The participants in a challenge trial are likely to be low risk as well, having been screened for health issues more thoroughly than any general population, as well as receiving medical monitoring and care which is far better than a typical population. For that reason, we use the best-case population as a conservative estimate of how much lower the risk for challenge trial participants might be compared to the general population - even after adjusting for comorbidities.

What does “potential treatment efficacy” mean?

The existence of an effective COVID-19 treatment could reduce the risks of death and hospitalization in a challenge trial. Our model lets users estimate the risks in a challenge trial with different levels of an effective COVID-19 treatment, which could become available between now and the commencement of a trial.

What data is this model based on?

Our model is based on an accepted paper by 1Day’s Research Team, Bayesian model of COVID-19 mortality risk in HCT volunteers. We look at data from multiple publicly available studies of COVID-19 infection fatality ratio among different populations.

What is a “micromort”?

A micromort represents a one-in-a-million risk of death. Our model uses micromorts to contextualize the short-term risks in a COVID-19 challenge trial with other frequent risks, such as childbirth and living kidney donation.

How many people are likely to actually take part in a COVID-19 human challenge trial?

The exact amount of participants in a COVID-19 challenge trial will depend on the length of the characterization study and the amount of vaccines being tested. The UK’s Human Challenge Programme, which began in March 2021, will involve up to 90 volunteers. Other challenge trials may vary in size.

How are risks to volunteers minimized?

The risk of harm is minimized to the extent possible by selecting people who are relatively young and who have no underlying health conditions. Study participants are also isolated in highly controlled environments under constant observation. If infection is detected, they are provided with the best available medical treatment.