colleagues were based on semi-quantitative enzyme-linked immunosorbent assays, where the read-out is in OD 450 units. As there is not an internal calibrator curve, the antibody levels cannot be expressed in a quantitative fashion. As a consequence, there are major limitations in comparing isotype-specific antibody levels with each other. This is particularly true when considering IgE, which usually represents only a minor fraction of the antibody repertoire.Using the quantitative ImmunoCAP assay, here we show that levels of anti-α-Gal IgE were log orders of magnitude lower than specific IgG in the five severe COVID-19 patients (Figure 1A).The recent article by Chen discussed the possibility that α-Gal could be used as a means of enhancing immune responses to COVID-19 vaccinations. 2 The concept, which takes advantage of pre-existing humoral immunity to α-Gal, is interesting and biologically plausible. Data cited in that report from nonhuman studies was also encouraging that α-Gal can indeed boost vaccine-related immune responses. Nonetheless, we were struck that there was no mention of the fact that IgE to α-Gal could be an important confounder to this strategy. IgE is a critical mediator of allergic reactions and IgE specific for α-Gal has been linked with cases of anaphylaxis that were caused by gelatin-containing vaccines (in which the gelatin was a source of α-Gal). 9,10 As α-Gal occurs in some areas of the world with frequencies approaching or exceeding 20%, there are good reasons to think that inclusion of α-Gal could lead to issues with vaccine safety. 5,11 We don′t doubt that α-Gal could have potential immuneenhancing benefits for certain personalized immunotherapies (e.g., cancer vaccines), but have reservations that it is a rational choice for designing vaccines that would be implemented widely on a population basis. 12