Ectodomain Shedding May Play a Pivotal Role in Disease Severity in COVID-19

Abstract

Ectodomain shedding mediated by a disintegrin and metalloprotease 10/17 (ADAM10/17) modulates the function of immune effector cells and may be involved in the novel coronavirus disease COVID-19. Toll-like receptor 7/8 (TLR7/8) recognizes single-strand RNA from viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) during the innate immune response [1], and TLR7/8 agonist activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate reactive oxygen species (ROS) [2]. ADAM10/7 was found to mediate ectodomain shedding to modulate immune responses [3] and to be activated by ROS [4]. These findings suggest that SARS-CoV-2 contributes to and induces ectodomain shedding, which may be associated with disease severity. In patients with COVID-19, studies found a higher blood concentration of the chemokine fractalkine [5]. Cell membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified as a binding site and entry receptor for the spike protein of SARS-CoV-2. After the