From COVID-19 to Sarcoidosis: How Similar Are These Two Diseases?

Abstract

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leads to the dysregulation of the immune system, exacerbates inflammatory responses, and even causes multiple organ dysfunction syndrome in patients with severe disease. Sarcoidosis is an idiopathic granulomatous multisystem disease characterized by dense epithelioid non-necrotizing lesions with varying degrees of lymphocytic inflammation. These two diseases have similar clinical manifestations and may also influence each other and affect their clinical courses. In this study, we analyzed some possible connections between sarcoidosis and COVID-19, including the role of the renin-angiotensin system in the respiratory system, immune response, and cell death pathways, to understand the underlying mechanisms of SARS-CoV-2 infection, predisposing patients to severe forms of COVID-19. This review will provide a new prospect for the treatment of COVID-19 and an opportunity to explore the pathogenesis and development of sarcoidosis.

Keywords: COVID-19; cell death pathways; granulomatous disease; renin–angiotensin system; sarcoidosis.

Figure 1

Common mechanistic of COVID-19 and sarcoidosis including RAS, immune responses, and cellular death pathways (autophagy, apoptosis, and PD-1/PD-L1 axis): increased concentrations of Ang II stimulate apoptosis and are negative regulators of autophagy. PD-1 increases the apoptosis of specific T cells in lymph nodes and decreases the apoptosis of regulatory T cells. RAS, renin–angiotensin system; Ang II, angiotensin II; PD-1, programmed cell death 1; IMMU, immune responses.

Figure 2

Function of RAS in the respiratory system on COVID-19 and sarcoidosis. Angiotensinogen is converted by renin to Ang I. Ang I is subsequently converted to Ang II by ACE, which is expressed on the surface of endothelial cells in the lung and kidney. Ang II in the pulmonary system promotes tissue repair and fibrosis, while it can also promote the occurrence of pulmonary edema and impair lung function. ACE2 negatively regulates the function of ACE by converting Ang I to Ang 1–9 and Ang II to Ang 1–7. ACEIs inhibit the production of Ang II and ARBs inhibit the binding of Ang II to angiotensin receptors. SARS-CoV-2 interacts with ACE2 and infects ACE2-expressing epithelial and endothelial cells in the lung and other organs, leading to the downregulation of ACE2. The downregulation of ACE2 leads to unopposed Ang II accumulation, which may accelerate the progress of COVID-19 via increased activity of RAS. Sarcoidosis granuloma epithelioid cells may be engaged in ACE biosynthesis, resulting in the elevation of serum ACE levels. The relationship between elevated ACE and sarcoidosis remains to be explored. RAS, renin–angiotensin system; ACE, angiotensin-converting enzyme; Ang I, angiotensin I; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers.