Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19

Bankar, Renuka; Suvarna, Kruthi; Ghantasala, Saicharan; Banerjee, Arghya; Biswas, Deeptarup; Choudhury, Manisha; Palanivel, Viswanthram; Salkar, Akanksha; Verma, Ayushi; Singh, Avinash; Mukherjee, Amrita; Pai, Medha Gayathri J; Roy, Jyotirmoy; Srivastava, Alisha; Badaya, Apoorva; Agrawal, Sachee; Shrivastav, Om; Shastri, Jayanthi; Srivastava, Sanjeeva

doi:10.1016/j.isci.2021.102135

Cited by 31 publications

(43 citation statements)

References 39 publications

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“…Disease severity was associated with increased, circulatory S100B protein levels as well (Aceti et al, 2020). So far, several multi-omics studies revealed that genes involved in neutrophil function and activation are highly upregulated and neutrophil degranulation is the most prominent defense pathway in SARS-CoV-2 infected patients (Akgun et al, 2020;Schulte-Schrepping et al, 2020;Bankar et al, 2021). Elevated levels of MPO in nasopharyngeal samples of COVID-19 patients were identified by proteomic analysis (Akgun et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients

Shrivastava

Chelluboina

Jedge

et al. 2021

Front. Cell. Infect. Microbiol.

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Understanding of the basis for severity and fatal outcome of SARS-CoV-2 infection is of paramount importance for developing therapeutic options and identification of prognostic markers. So far, accumulation of neutrophils and increased levels of pro-inflammatory cytokines are associated with disease severity in COVID-19 patients. In this study, we aimed to compare circulatory levels of neutrophil secretory proteins, alpha-defensins (DEFA1), calprotectin (S100A8/A9), and myeloperoxidase (MPO) in COVID-19 patients with different clinical presentations. We studied 19 healthy subjects, 63 COVID-19 patients with mild (n=32) and severe (n=31) disease, 23 asymptomatic individuals identified through contact tracing programme and 23 recovering patients (1-4 months post-disease). At the time of disease presentation, serum levels of DEFA1 were significantly higher in patients with mild (mean230 ± 17, p<0.0001) and severe (mean452 ± 46, p<0.0001) disease respectively in comparison to healthy subjects (mean113 ± 11). S100A8/A9 proteins were significantly higher in COVID-19 patients (p<0.0001) irrespective of disease severity. The levels of DEFA1, S100A8/A9 and MPO reduced to normal in recovering patients and comparable to healthy subjects. Surprisingly, DEFA1 levels were higher in severe than mild patients in first week of onset of disease (p=0.004). Odds-ratio analysis showed that DEFA1 could act as potential biomarker in predicting disease severity (OR=11.34). In addition, levels of DEFA1 and S100A8/A9 were significantly higher in patients with fatal outcome (p=0.004 and p=0.03) respectively. The rise in DEFA1 levels was independent of secondary infections. In conclusion, our data suggest that induction of elevated levels of alpha-defensins and S100A8/A9 is associated with poor disease outcome in COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients

Shrivastava

Chelluboina

Jedge

et al. 2021

Front. Cell. Infect. Microbiol.

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“… 24 In our previous proteomic study, we have observed an increase in the expression of IL-6 and CRP in severe patients using swab samples. 25 …”

Section: Discussionmentioning

confidence: 99%

A Multi-omics Longitudinal Study Reveals Alteration of the Leukocyte Activation Pathway in COVID-19 Patients

et al. 2021

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Severe coronavirus disease 2019 (COVID-19) infection may lead to lung injury, multi-organ failure, and eventually death. Cytokine storm due to excess cytokine production has been associated with fatality in severe infections. However, the specific molecular signatures associated with the elevated immune response are yet to be elucidated. We performed a mass-spectrometry-based proteomic and metabolomic analysis of COVID-19 plasma samples collected at two time points. Using Orbitrap Fusion LC–MS/MS-based label-free proteomic analysis, we identified around 10 significant proteins, 32 significant peptides, and 5 metabolites that were dysregulated at the severe time points. Few of these proteins identified by quantitative proteomics were validated using the multiple reaction monitoring (MRM) assay. Integrated pathway analysis using distinct proteomic and metabolomic signatures revealed alterations in complement and coagulation cascade, platelet aggregation, myeloid leukocyte activation pathway, and arginine metabolism. Further, we highlight the role of leukocyte activation and arginine metabolism in COVID-19 pathogenesis and targeting these pathways for COVID-19 therapeutics.

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“…GO and REACTOME pathway enrichment analyses were performed to explore interactions among the DEGs. Pathways include immune system [83], adaptive immune system [84], neutrophil degranulation [85], cytokine signaling in immune system [86] and GPCR ligand binding [87] were responsible for progression of COVID-19 infection. A previous study demonstrated that the expression levels of AHSP (alpha hemoglobin stabilizing protein) [88], IL7R [89], FBXO7 [90], KLRB1 [91], PIP4K2A [92], NFE2 [93], CCR2 [94], CLEC12A [95], NLRP12 [96], PECAM1 [97], TRIM10 [98], ICAM3 [99], EEF1A1 [100], CCR4 [101], PTPRC (protein tyrosine phosphatase receptor type C) [102], CX3CR1 [103], TSPAN32 [104], EOMES (eomesodermin) [105], ATM (ATM serine/threonine kinase) [106], CD28 [107], LRRK2 [108], CCL5 [109], CD33 [110], FCRL3 [111], CCR3 [112], FGL2 [113], GZMA (granzyme A) [114], PICALM (phosphatidylinositol binding clathrin assembly protein) [115], ALOX5 [116], MME (membrane metalloendopeptidase) [117], VIM (vimentin) [118], CD93 [119], GCA (grancalcin) [120], CD226 [121], CD1D [122], TNFSF4 [123], LEF1 [124], TLR4 [125], CCR7 [126], DPP4 [127], NLRC4 [128], ITGB3 [129], RASGRP1 [130], TLR2 [131], DOCK2 [132], CSF1R [133], PRKCB (protein kinase C beta) [134], CAMK4 [135], CXCL5 [136], CD36 [137], P2RY12 [138], LILRB2 [139], CD5 [140], SLC25A37 [141], ADIPOR1 [142], PECAM1 [143], RGS10 [144], RGS18 [145], ANK1 [146], RNF182 [147], NPRL3 [148], NINJ2 [149], KCNA3 [150], ABCG2 [151], MS4A6A […”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of next-generation sequencing data in COVID-19 and its secondary complications

Vastrad¹,

Vastrad²

2022

Preprint

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The ongoing pandemic of coronavirus disease 2019 (COVID-19) has made a serious public health threat globally. To discover key molecular changes in COVID-19 and its secondary complications, we analyzed next-generation sequencing (NGS) data of COVID-19. NGS data (GSE163151) was screened and downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were identified in the present study, using DESeq2 package in R programming software. Gene ontology (GO) and pathway enrichment analysis were performed, and the protein-protein interaction (PPI) network, module analysis, miRNA-hub gene regulatory network and TF-hub gene regulatory network were established. Subsequently, receiver operating characteristic curve (ROC) analysis was used to validate the diagonostics valuesof the hub genes. Firstly, 954 DEGs (477 up regulated and 477 down regulated) were identified from the four NGS dataset. GO enrichment analysis revealed enrichment of DEGs in genes related to the immune system process and multicellular organismal process, and REACTOME pathway enrichment analysis showed enrichment of DEGs in the immune system and formation of the cornified envelope. Hub genes were identified from the PPI network, module analysis, miRNA-hub gene regulatory network and TF-hub gene regulatory network. Furthermore, the ROC analysis indicate that COVID-19 and its secondary complications with following hub genes, namely, RPL10, FYN, FLNA, EEF1A1, UBA52, BMI1, ACTN2, CRMP1, TRIM42 and PTCH1, had good diagnostics values. This study identified several genes associated with COVID-19 and its secondary complications, which improves our knowledge of the disease mechanism.

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Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19

Cited by 31 publications

References 39 publications

Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients

Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients

A Multi-omics Longitudinal Study Reveals Alteration of the Leukocyte Activation Pathway in COVID-19 Patients

Comprehensive analysis of next-generation sequencing data in COVID-19 and its secondary complications

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