Considering over-activation of ADAM17 in COVID-19 [10] and its role in both shedding of mACE2 and IL-6-induced inflammatory responses [232] it seems that the lack of strong correlation between sACE2 level and inflammatory markers (IL-6) might be due to the saturable nature of ADAM17-dependent shedding of mACE2 (see Section 9) [168]; sACE2 does not rise to the level of increasing the activation of ADAM17 which is responsible for the raised IL-6-dependent signaling, as well. The gene discussed is ADAM17; the disease is COVID-19.