Table I.
Evidence summarizing potential mechanistic links between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and abdominal aortic aneurysms (AAAs)
| Evidence category | Evidence | References |
|---|---|---|
| Common risk factors | Male sex, advanced age, cigarette smoking Chronic obstructive pulmonary disease and obesity |
7, 8, 9, 10, 11, 12, 13, 14, 15 |
| Effects on/consequences of RAS dysregulation. | ACE-Ang II-AT1 receptor activity promotes, whereas ACE2-Ang 1-7-Mas receptor activity inhibits, experimental AAAs Reduced clinical AAA expansion associated with ARB use ACE2 expression is reduced in aneurysmal aorta. Apelin and resveratrol, protective against experimental AAA, increases ACE2 expression. Circulating ACE2 inversely associated with AAA risk and operative mortality following repair. Cell surface ACE2 internalization and shedding following SARS-CoV-2 entry impairs Ang II degradation and Ang 1-7 formation. Increased Ang II and reduced Ang 1-7 serum levels in patients with COVID-19. |
1,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 |
| Influences on/effects of inflammatory mediator expression | SARS-CoV-2-infected cells (respiratory epithelial cells, vascular endothelial cells, smooth muscle cells and fibroblasts) secrete chemokines and cytokines such as CCL2, CXCL12, MIF, IL-1β, TNF-α, IL-6, IL-8, type 1 interferons Recognition of chemokines and cytokines by their myeloid cell receptors mediates myeloid cell migration and inflammatory activity |
45, 46, 47, 48 |
| Biologic response to viral spike protein exposure. | Spike protein exposure increases IL-1β, IL-6, IL-8, IL-12, TNF-α, MHC II, and costimulatory molecule (CD80 and CD86) expression by ACE2-neagtive macrophages and dendritic cells, augmenting their inflammatory and T cell-stimulatory activity | 49, 50, 51, 52, 53, 54, 55 |
| SARS-CoV-2 RNA recognized by TLR7 and TLR8 | TLR signaling triggers proinflammatory type 1 interferon production by infected ACE2-expressing cells and impact leukocyte activity by interacting with their leukocyte type 1 receptor Directly or indirectly influence interferon regulatory factor expression on T cells and macrophages promoting the differentiation or activation of proinflammatory Th1 cells, Th17 cells and M1 macrophages |
49,56 |
| Viral pulmonary injury | Pulmonary injury creates hypoxemia stabilizing and increasing proaneurysmal HIF-1 levels Increases LPS owing to secondary pulmonary bacterial infection |
13,56, 57, 58, 59, 60, 61, 62, 63, 46 |
| Other | Intracranial and coronary arterial aneurysms have been reported in adults and children, respectively, with COVID-19 | 64, 65, 66, 67 |
ACE, Angiotensin-converting enzyme; Ang, angiotensin; COVID-19, coronavirus disease-2019; HIF, hypoxia-inducible factor; LPS, lipopolysaccharide; MHC, major histocompatibility complex; RAS, renin-angiotensin system; Th, T helper cell; TLR, Toll-like receptor; TNF, tumor necrosis factor.