The hypothesis we posit is that thalassemia traits in general, and particularly HbE, are protective against COVID-19 infection in similar ways to the numerous thalassemia traits conferring protection against malaria [30,42] and the dengue virus [43]. Herd immunity development traditionally requires that 60% of the population becomes homogeneously infected by or vaccinated against an infectious disease. However, recent mathematical models introducing age and activity heterogeneities into population models predict that herd immunity can be achieved at 43% [44], a level substantially lower than the observed prevalence of HbE in some areas of SE Asia [13–15]. In fact, in countries where the HbE trait is above 43%, the numbers of both COVID-19 infections and deaths have been minimal (Table 1, Figures 1, 2).