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Circulating Peptidome Is Strongly Altered in COVID-19 Patients.

ABSTRACT: Whilst the impact of coronavirus disease 2019 (COVID-19) on the host proteome, metabolome, and lipidome has been largely investigated in different bio-fluids, to date, the circulating peptidome remains unexplored. Thus, the present study aimed to apply an untargeted peptidomic approach to provide insight into alterations of circulating peptides in the development and severity of SARS-CoV-2 infection. The circulating peptidome from COVID-19 severe and mildly symptomatic patients and negative controls was characterized using LC-MS/MS analysis for identification and quantification purposes. Database search and statistical analysis allowed a complete characterization of the plasma peptidome and the detection of the most significant modulated peptides that were impacted by the infection. Our results highlighted not only that peptide abundance inversely correlates with disease severity, but also the involvement of biomolecules belonging to inflammatory, immune-response, and coagulation proteins/processes. Moreover, our data suggested a possible involvement of changes in protein degradation patterns. In the present research, for the first time, the untargeted peptidomic approach enabled the identification of circulating peptides potentially playing a crucial role in the progression of COVID-19.

SUBMITTER: Baldanzi G

PROVIDER: S-EPMC9865723 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Circulating Peptidome Is Strongly Altered in COVID-19 Patients.

Baldanzi Gianluca G Purghè Beatrice B Ragnoli Beatrice B Sainaghi Pier Paolo PP Rolla Roberta R Chiocchetti Annalisa A Manfredi Marcello M Malerba Mario M

International journal of environmental research and public health 20230114 2

Whilst the impact of coronavirus disease 2019 (COVID-19) on the host proteome, metabolome, and lipidome has been largely investigated in different bio-fluids, to date, the circulating peptidome remains unexplored. Thus, the present study aimed to apply an untargeted peptidomic approach to provide insight into alterations of circulating peptides in the development and severity of SARS-CoV-2 infection. The circulating peptidome from COVID-19 severe and mildly symptomatic patients and negative cont ...[more]

PMID: 36674321

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Project description:The lack of available biomarkers for diagnosing and predicting different stages of coronavirus disease 2019 (COVID-19) is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific miRNAs may be significantly modified in COVID-19 patients. Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (between March and May 2020) (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. Patients were categorized as hospitalized not requiring oxygen therapy (n = 6), hospitalized requiring low-flow oxygen (n = 23), and hospitalized requiring high-flow oxygen support (n = 11). A total of 1218 different micro(mi)RNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2 infected patients showed significantly (fold change [FC] >1.2 and adjusted p [padj] <0.05) altered expression of 190 miRNAs. The top 10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found when patients on high- and low-flow oxygen therapy were compared. Similarly, 6 DE miRNAs were identified between patients on high flow and those not requiring oxygen therapy. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Furthermore, specific miRNA profiles are associated with COVID-19 prognosis in severe patients.

Project description: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.

Project description:BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant loss of life and property. In response to the serious pandemic, recently developed vaccines against SARS-CoV-2 have been administrated to the public. Nevertheless, the research on human immunization response against COVID-19 vaccines is insufficient. Although much information associated with vaccine efficacy, safety and immunogenicity has been reported by pharmaceutical companies based on laboratory studies and clinical trials, vaccine evaluation needs to be extended further to better understand the effect of COVID-19 vaccines on human beings.MethodsWe performed a comparative peptidome analysis on serum samples from 95 participants collected at four time points before and after receiving CoronaVac. The collected serum samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to profile the serum peptides, and also subjected to humoral and cellular immune response analyses to obtain typical immunogenicity information.ResultsSignificant difference in serum peptidome profiles by MALDI-TOF MS was observed after vaccination. By supervised statistical analysis, a total of 13 serum MALDI-TOF MS feature peaks were obtained on day 28 and day 42 of vaccination. The feature peaks were identified as component C1q receptor, CD59 glycoprotein, mannose-binding protein C, platelet basic protein, CD99 antigen, Leucine-rich alpha-2-glycoprotein, integral membrane protein 2B, platelet factor 4 and hemoglobin subunits. Combining with immunogenicity analysis, the study provided evidence for the humoral and cellular immune responses activated by CoronaVac. Furthermore, we found that it is possible to distinguish neutralizing antibody (NAbs)-positive from NAbs-negative individuals after complete vaccination using the serum peptidome profiles by MALDI-TOF MS together with machine learning methods, including random forest (RF), partial least squares-discriminant analysis (PLS-DA), linear support vector machine (SVM) and logistic regression (LR).ConclusionsThe study shows the promise of MALDI-TOF MS-based serum peptidome analysis for the assessment of immune responses activated by COVID-19 vaccination, and discovered a panel of serum peptides biomarkers for COVID-19 vaccination and for NAbs generation. The method developed in this study can help not only in the development of new vaccines, but also in the post-marketing evaluation of developed vaccines.

Dataset Information

Circulating Peptidome Is Strongly Altered in COVID-19 Patients.

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Circulating Peptidome Is Strongly Altered in COVID-19 Patients.

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