TMPRSS2 facilitates SARS-CoV-2 infection via cleavage of the S protein at the cleavage at S1/S2 and S2’ sites in an acidic cellular environment. Inhibitors of endosomal acidification, which causes this phenomenon, include CatB/L, E-64D, hydroxychloroquine, and chloroquine. These drugs may only work for COVID-19 patients who are TMPRSS2-absent and may be less effective or not effective at all for wild type TMPRSS2. Populations such as African AMericans and non-Finnish Europeans carry missense and stop-gained polymorphisms on the TMPRSS2 gene that may make them more susceptible to hydroxychloroquine and chloroquine treatment.