Proteomics Analysis of Serum from COVID-19 Patients

Liu, Xiaoling; Cao, Yinghao; Fu, Hongmei; Wei, Jie; Chen, Jianhong; Hu, Jun; Liu, Bende

doi:10.1021/acsomega.1c00616

Cited by 22 publications

(19 citation statements)

References 24 publications

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“…Among them, CETP was up-regulated in the serum of asymptomatic individuals, as previously seen in COVID-19 patients with mild symptoms (Liu et al 2021 ), while in the serum of critical patients this protein appeared down-regulated (Shu et al 2020 ). CETP mediates lipid exchange (Satoh et al 2016 ), but it also inhibits prolonged inflammation.…”

Section: Discussionsupporting

confidence: 65%

The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo

Beltrán-Camacho

Eslava-Alcon

Rojas-Torres

et al. 2022

Mol Med

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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.

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Section: Discussionsupporting

confidence: 65%

The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo

Beltrán-Camacho

Eslava-Alcon

Rojas-Torres

et al. 2022

Mol Med

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“…Examples of these biomarkers are serum amyloid A-1 (SAA1), serum amyloid A-2 (SAA2), C-reactive protein (CRP), gelsolin (GSN), interleukins (IL-1, IL-6), serine protease inhibitors (SERPINs), progranulin (GRN), apolipoproteins (APOs), complement and pro-inflammatory factors, coagulation system, and vascular cell adhesion protein 1 (VCAM-1) ( 4 – 23 ). Results of proteomics analyses have shown a correlation of disease severity with inflammatory, immunological, and cancer biomarkers, metabolic suppression, neutrophil activation, hepatic and lung injury and the dysregulation of lipid transport, macrophages, platelet degranulation, and complement system pathways ( 4 – 6 , 8 – 13 , 18 , 20 – 22 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology

et al. 2021

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The COVID-19 pandemic caused by SARS-CoV-2 challenges the understanding of factors affecting disease progression and severity. The identification of prognostic biomarkers and physiological processes associated with disease symptoms is relevant for the development of new diagnostic and therapeutic interventions to contribute to the control of this pandemic. To address this challenge, in this study, we used a quantitative proteomics together with multiple data analysis algorithms to characterize serum protein profiles in five cohorts from healthy to SARS-CoV-2-infected recovered (hospital discharge), nonsevere (hospitalized), and severe [at the intensive care unit (ICU)] cases with increasing systemic inflammation in comparison with healthy individuals sampled prior to the COVID-19 pandemic. The results showed significantly dysregulated proteins and associated biological processes and disorders associated to COVID-19. These results corroborated previous findings in COVID-19 studies and highlighted how the representation of dysregulated serum proteins and associated BPs increases with COVID-19 disease symptomatology from asymptomatic to severe cases. The analysis was then focused on novel disease processes and biomarkers that were correlated with disease symptomatology. To contribute to translational medicine, results corroborated the predictive value of selected immune-related biomarkers for disease recovery [Selenoprotein P (SELENOP) and Serum paraoxonase/arylesterase 1 (PON1)], severity [Carboxypeptidase B2 (CBP2)], and symptomatology [Pregnancy zone protein (PZP)] using protein-specific ELISA tests. Our results contributed to the characterization of SARS-CoV-2–host molecular interactions with potential contributions to the monitoring and control of this pandemic by using immune-related biomarkers associated with disease symptomatology.

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“…Glutamine, is the most abundant amino acid in plasma, is used as a source of energy, carbon, and nitrogen to support cellular homeostasis [ 41 – 43 ]. It is an indispensable nitrogen donor for the de novo synthesis of hexosamines such as purine, pyrimidine, non-essential amino acids, glucosamine and galactosamines [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%