The serum of COVID-19 asymptomatic patients in circulating angiogenic cells ex-vivo

ABSTRACT: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has provoked, up to date, more than 5 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 in the actual pandemic. Moreover, apart from the effect over the respiratory system, 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 in response to the virus as well as the potential sequelae at the long term, even in asymptomatic donors, becomes essential. Methods: We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum of COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Thus, 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. 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. Many of these proteins correlate with the initial response of the endothelium against the virus. Conclusions: The incubation ex vivo 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 that occur 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, as well as an alternative to test potential inhibitors targeting either the virus entry pathway or molecules involved in the immune responses following SARS-CoV-2 infection.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Adult Endothelial Progenitor Cell, Blood Serum

DISEASE(S): Severe Acute Respiratory Syndrome

SUBMITTER: Carmen Duran  

LAB HEAD: Duran-Ruiz, Carmen

PROVIDER: PXD030860 | Pride | 2022-05-20

REPOSITORIES: Pride