Abstract
The renin-angiotensin system (RAS) plays a major role in COVID-19. Severity of several inflammation-related diseases has been associated with autoantibodies against RAS, particularly agonistic autoantibodies for angiotensin type-1 receptors (AA-AT1) and autoantibodies against ACE2 (AA-ACE2). Disease severity of COVID-19 patients was defined as mild, moderate or severe following the WHO Clinical Progression Scale and determined at medical discharge. Serum AA-AT1 and AA-ACE2 were measured in COVID-19 patients (n = 119) and non-infected controls (n = 23) using specific solid-phase, sandwich enzyme-linked immunosorbent assays. Serum LIGHT (TNFSF14; tumor necrosis factor ligand superfamily member 14) levels were measured with the corresponding assay kit. At diagnosis, AA-AT1 and AA-ACE2 levels were significantly higher in the COVID-19 group relative to controls, and we observed significant association between disease outcome and serum AA-AT1 and AA-ACE2 levels. Mild disease patients had significantly lower levels of AA-AT1 (p < 0.01) and AA-ACE2 (p < 0.001) than moderate and severe patients. No significant differences were detected between males and females. The increase in autoantibodies was not related to comorbidities potentially affecting COVID-19 severity. There was significant positive correlation between serum levels of AA-AT1 and LIGHT (TNFSF14; r Pearson = 0.70, p < 0.001). Both AA-AT1 (by agonistic stimulation of AT1 receptors) and AA-ACE2 (by reducing conversion of Angiotensin II into Angiotensin 1-7) may lead to increase in AT1 receptor activity, enhance proinflammatory responses and severity of COVID-19 outcome. Patients with high levels of autoantibodies require more cautious control after diagnosis. Additionally, the results encourage further studies on the possible protective treatment with AT1 receptor blockers in COVID-19.
Keywords: Autoantibody; Autoimmunity; LIGHT; Outcome prediction; Renin-angiotensin system; SARS-CoV-2.
【저자키워드】 Autoimmunity, SARS-CoV-2., renin-angiotensin system, autoantibody, LIGHT, Outcome prediction, 【초록키워드】 COVID-19, Treatment, SARS-CoV-2, Necrosis, ACE2, COVID-19 severity, Diagnosis, Proinflammatory response, Comorbidity, outcome, discharge, RAS, serum, severity of COVID-19, enzyme-linked immunosorbent assays, clinical, male, Patient, Control, Mild, receptors, receptor, scale, disease, moderate, Protective, Mild disease, association, Angiotensin II, Ligand, AT1, angiotensin, COVID-19 patient, significant difference, severe patients, Serum level, positive correlation, COVID-19 group, blocker, Pearson, significantly lower, females, controls, non-infected, ENhance, defined, reducing, increase in, significantly higher, the WHO, affecting, were measured, 【제목키워드】 ACE2, severity of COVID-19, receptor,