RT journal article T1 The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo A1 Beltrán Camacho, Lucía A1 Eslava Alcón, Sara A1 Rojas Torres, Marta A1 Sánchez Morillo, Daniel A1 Martinez‑Nicolás, Mª Pilar A1 Martín‑Bermejo, Victoria A1 García de la Torre, Inés A1 Berrocoso Domínguez, Esther María A1 Moreno, Juan Antonio A1 Moreno Luna, Rafael A1 Durán Ruiz, María del Carmen A2 BiomedicinaBiotecnología y Salud Pública A2 Ingeniería en AutomáticaElectrónica, Arquitectura y Redes de Computadores A2 Psicología K1 COVID-19 K1 SARS-CoV-2 K1 Endothelial progenitor cells K1 Circulating angiogenic cells K1 Proteomics K1 Endothelial dysfunction K1 Asymptomatic AB Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential. Methods We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR -/IgG -, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG - (n:8) and PCR -/IgG + (n:8). Also, a label free quantitative approach was applied to identify and quantify protein differences between these serums. Finally, machine learning algorithms were applied to validate the differential protein patterns in CACs. Results Our results confirmed that SARS-CoV-2 promotes changes at the protein level in the serum of infected asymptomatic individuals, mainly correlated with altered coagulation and inflammatory processes (Fibrinogen, Von Willebrand Factor, Thrombospondin-1). At the cellular level, proteins like ICAM-1, TLR2 or Ezrin/Radixin were only up-regulated in CACs treated with the serum of asymptomatic patients at the highest peak of infection (PCR + /IgG -), but not with the serum of PCR -/IgG + individuals. Several proteins stood out as significantly discriminating markers in CACs in response to PCR or IgG + serums. Many of these proteins particiArticle title: Kindly check and confirm the edit made in the article title.pate in the initial endothelial response against the virus. Conclusions The ex vivo incubation of CACs with the serum of asymptomatic COVID-19 donors at different stages of infection promoted protein changes representative of the endothelial dysfunction and inflammatory response after viral infection, together with activation of the coagulation process. The current approach constitutes an optimal model to study the response of vascular cells to SARS-CoV-2 infection, and an alternative platform to test potential inhibitors targeting either the virus entry pathway or the immune responses following SARS-CoV-2 infection. PB SPRINGER SN 1076-1551 YR 2022 FD 2022-12 LK http://hdl.handle.net/10498/26916 UL http://hdl.handle.net/10498/26916 LA eng DS Repositorio Institucional de la Universidad de Cádiz RD 10-may-2026