Alex Moir ’23

SARS-CoV-2 is the virus currently driving the COVID-19 pandemic. SARS-CoV-2 has been shown to infect ciliated epithelial cells (EPCs), which line the upper respiratory tract, through a cell surface receptor known as angiotensin-converting enzyme 2 (ACE2), resulting in Acute Respiratory Distress Syndrome (ARDS). ARDS is characterized by both pulmonary and vascular dysregulation, which presents as shortness of breath, low oxygen, and poor circulation. It is currently unclear whether the vascular components of ARDS pathology are the result of direct infection of the endothelial cells (ECs) that make up the blood vessel walls, or changes in how infected EPCs interact with and influence ECs along the epithelial-endothelial barrier in alveoli. To determine whether ARDS-associated vascular dysregulation is directly or indirectly caused by SARS-CoV-2 infection of ECs, Stony Brook researcher Dr. Erich R. Mackow and his team investigated the expression of ACE2 throughout the endothelium, or the population of ECs that line the inside of blood vessels. 

The team first isolated EC populations from COVID-19 patient lung, heart, kidney, brain, and umbilical vein tissue samples, and immunostained them for N and Spike SARS-CoV-2 antigens. Analysis revealed no positive staining for these markers of SARS-CoV-2 cellular infection. Analysis of EC-based qRT-PCR and western blots, which search for specific target RNA and proteins respectively, also showed no presence of the ACE2 receptor. The researchers then engineered primary human pulmonary and brain ECs to express ACE2 and exposed the ACE2-expressing EC cultures to SARS-CoV-2. Immunostaining revealed the presence of N antigens and colocalization of virus with ACE2 in the ACE2-expressing ECs. Additionally, analysis of results from mRNA sequencing of infected ACE2-expressing ECs revealed increased expression of several coagulation and vascular inflammation factors associated with ARDS vascular pathology. 

The researcher’s findings provide compelling evidence that ECs do not express ACE2, which is essential for SARS-CoV-2 docking and infection of cells. Additionally, they demonstrate that SARS-CoV-2 infection is dependent on ACE2 expression, and that while SARS-CoV-2 is able to affect ECs, the pathogen is unable to infect those cells in vivo as they don’t express the ACE2 receptor. These findings also suggest that the vascular component of ARDS pathology is not the result of direct EC infection by SARS-CoV-2. However, the mRNA sequencing results hint that small subpopulations of SARS-CoV-2 infected ECs may still play a role in ARDS vascular pathology, meriting future investigation. 

Works Cited:

[1] J. Conde, et al., Recombinant ACE2 expression is required for SARS-CoV-2 to infect primary human endothelial cells and induce inflammatory and procoagulative responses. mBio 11, 1-7 (2020). doi: /10.1128/mBio.03185-20.[2] Image retrieved from: https://unsplash.com/photos/Pw9aFhc92P8