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Objective: To review similarities between COVID-19 and systemic sclerosis (SSc) early vasculopathy to provide novel insights into both diseases., Methods: A narrative review of the literature supplemented with expert opinion., Results: There is clear evidence that the endothelium is at the centre stage in SSc and COVID-19, with endothelial cell activation/injury and dysfunction creating the crucial evolving step in the pathogenesis of both diseases. The angiotensin system has also been implicated in the early stages of both COVID-19 and SSc. Autoptic studies provide novel insights into the effects of SARS-CoV-2 on the endothelium. Normal endothelium and endothelial dysfunction in COVID-19 and SSc are discussed. It is debated whether SARS-CoV-2 infection triggers autoimmunity with production of autoantibodies which is of mechanistic interest because other viral illnesses are potentially involved in endothelial dysfunction and in SSc pathogenesis., Conclusion: COVID-19 is due to a direct assault of SARS-CoV-2 on the vascular system as an acute infection, whereas SSc remains a chronic/sub-acute autoimmune disease of largely unknown etiology Further study and exploration of the SARS-CoV-2 pathogenic mechanisms might provide further useful milestones in the understanding of the early SSc pathogenesis., (Copyright © 2021. Published by Elsevier B.V.)

Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure. Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. In this work, the growing body of evidence is summarized regarding the predictive factors for drug response in patients with AIDs, applying the precision medicine principles to provide high-quality evidence for therapeutic opportunities in improving the management of these patients., (Copyright © 2020. Published by Elsevier B.V.)

Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may play an important role in atherogenesis. Inflammation and complement depositions in the vessel wall are likely to contribute to vascular stiffness. Based on biopsy findings, also inflammation in the myocardium and small vessels may contribute to premature CVD in ARDs (cardiac ischemia and heart failure). There is an enormous need for an improved CVD prevention in ARDs. Studies examining the effect of DMARDs/biologics on vascular inflammation and CV risk are warranted., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Vascular endothelial injury in systemic sclerosis (SSc) includes a spectrum of changes that involve predominantly the microcirculation and arterioles. The pathologic changes in the blood vessels adversely impact the physiology of many organ systems, with a reduction in the size of microvascular beds leading to decreased organ blood flow and ultimately to a state of chronic ischemia. Current hypotheses in SSc vascular disease suggest a possible chemical or infectious trigger.

An elevated level of von Willebrand factor (vWf) is a well-established marker for both in vivo and in vitro endothelial cell injury. Recent studies indicate that the plasma level of angiotensin-converting enzyme (ACE) in systemic sclerosis is reduced in association with elevated vWf levels. Because the endothelial cell is capable of producing both mediators, and because endothelial cell injury is a fundamental process in systemic sclerosis, we investigated in this study the effect of in vitro endothelial cell injury on the synthesis of both factors. Endothelial cells derived from human umbilical veins, in the second passage, were activated by exposure to interleukin-1 or lymphotoxin or were injured by radiation, actinomycin, or trypsin (each can be shown to induce dose-dependent endothelial cell cytotoxicity). ACE (spectrophotometric method) and vWf levels (enzyme-linked immunosorbent assay method) were determined in the supernatant and in the cell lysate 48 hours after cellular injury and activation. An increase in vWf levels was found in the lysate and in the supernatant from the cells that underwent injury or activation, whereas ACE levels were increased after activation but decreased after injury. Next, and as an in vivo clinical corollary to the in vitro endothelial cell injury, we evaluated ACE and vWf levels in the plasma of seven children in the acute phase of Kawasaki disease, a disorder characterized by widespread vascular injury. Plasma ACE levels were significantly lower than control levels, whereas vWf levels were increased, reflecting the known prominent endothelial cell injury in this disease.(ABSTRACT TRUNCATED AT 250 WORDS)