Expression of ACE2 in Human Neurons Supports the Neuro-Invasive Potential of COVID-19 Virus

Abstract

The recent outbreak of 2019 coronavirus disease (COVID-19), caused by a novel coronavirus, has now spread quickly worldwide. Like the severe acute respiratory syndrome coronavirus (SARS-CoV), this novel type of coronavirus, SARS-CoV-2, has been demonstrated to utilize angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. There is a growing body of reports indicating that COVID-19 patients, especially those in severe condition, exhibit neurological symptoms, thus supporting the possibility that SARS-CoV-2 could infect and damage neurons within the central nervous system in humans. Using human pluripotent stem cells-derived neurons, here we show the expression of ACE2 in human neurons via immunocytochemistry. From this perspective, we elaborate on the idea that the neuro-invasive potential of SARS-CoV-2 should be considered as a possible contributory factor, as well as a therapeutic target, for the severe respiratory symptoms in critical COVID-19 cases.

Keywords: ACE2; COVID-19; Central nervous system; Neurons; SARS-CoV-2.

Fig. 1

ACE2 expresses in human neurons, therefore COVID-19 virus could invade the CNS, causing neurological symptoms and respiratory failure. (a) ACE2 expresses in cultured human pluripotent stem cell (PSC)-derived mixed neurons. A₁: A bright field image of cultured human PSC-derived neurons (STEMCELL, 70905, Canada). The scale bar represents 20 μm. A_2–3: Immunofluorescent labeling for visualization of ACE2 (red) in cultured human PSC-derived neurons (blue: DAPI). The scale bars represent 20 μm in (A₂) and 10 μm in (A₃), respectively. The specimens were incubated with rabbit anti-mouse ACE2 antibody (1:100 dilution; Aviva System Biology, OASG00144, CA, USA) overnight at 4 ºC. (b) A schematic of how neuronal ACE2 could contribute to coronavirus-related respiratory diseases