Editorial: The Need for Harmonised International Guidelines ahead of COVID-19 Human Infection Studies

Abstract

As evidenced by the October 2020 British go ahead for potential controlled human infection studies (CHIMs) (www.imperial.ac.uk/news/206893/uk-researchers-explore-human-challenge-studies/) and the publication of World Health Organization (WHO) criteria for COVID-19 CHIMs in May 2020 [1], the current pandemic may not only test the ethical limits of medical research but also open the door for much-needed globally-consistent guidance. Also known as human challenge or infection studies, the idea behind CHIMs is to infect carefully monitored healthy volunteers with a pathogen to test novel treatments and vaccines. Rather than rolling out a new vaccine to thousands of people and relying on uncontrolled natural infections, CHIMs promise a much more rapid evaluation of efficacy in comparatively safe circumstances. The history of CHIMs is closely tied to vaccine development. When English physician Edward Jenner developed a cowpox vaccine against the deadly smallpox virus in 1796, he decided to test its efficacy on his gardener’s son, James Phipps [2]. Phipps received a cowpox inoculation and was later exposed to smallpox scabs. Phipps’ lack of illness or characteristic smallpox scaring indicated that the new vaccine was effective. The advent of germ theory led to more systematic CHIMs. When British scientist Almroth Wright developed a vaccine against typhoid in 1896, he tested the vaccine by first inocculating himself and colleagues and then challenging at least one person with an injection of live typhoid bacteria [3]. Between 1946 and 1989, Britain’s Common Cold Unit infected over 20,000 volunteers with common cold viruses [4]. Although the trials did not result in a proven vaccine, they improved knowledge of respiratory viruses and led to an anti-influenza compound [4]. Newer typhoid vaccines have also been tested with CHIMs, and CHIMs have been used to trial vaccines for other diseases like cholera and influenza. There is clear evidence that CHIMs can speed-up research, but there are limitations to what information they can provide. Commentators have noted that using CHIM data from small groups of volunteers as a predictor of vaccine and therapy efficacy in the field is not straightforward: target populations will have varying microbiota, genetic profiles, and different co-morbidities like malnutrition, obesity, or burdens from other infectious or noninfectious diseases [5]. Small sample sizes will pose an inevitable problem for any CHIM involving COVID-19. Current plans for British CHIMs by Imperial College, the Department for Business, Energy and Industrial Strategy (BEIS), and clinical company (hVIVO) include a virus characterisation study and then studying how COVID-19 vaccines work. In the case of Edited and reviewed by: Raquel Lucas, University Porto, Portugal