COVID-19 poses an exceptional threat to global public health and well-being. Recognition of the need to develop effective vaccines at unprecedented speed has led to calls to accelerate research pathways ethically, including by conducting challenge studies ) with SARS-CoV-2. Such research is controversial, with concerns being raised about the social, legal, ethical and clinical implications of infecting healthy volunteers with SARS-CoV-2 for research purposes. Systematic risk evaluations are critical to inform assessments of the ethics of any proposed SARS-CoV-2 CHIs. Such (...) evaluations will necessarily take place within a rapidly changing and at times contested epidemiological landscape, in which differing criteria for the ethical acceptability of research risks have been proposed. This paper critically reviews two such criteria and evaluates whether the use of effective treatment should be a necessary condition for the ethical acceptability of SARS-CoV-2 CHIs, and whether the choice of study sites should be influenced by COVID-19 incidence levels. The paper concludes that ethical evaluations of proposed SARS-CoV-2 CHIs should be informed by rigorous, consultative and holistic approaches to systematic risk assessment. (shrink)