Dataset Information

Proteomic Investigation Reveals Dominant Alterations of Neutrophil Degranulation and mRNA Translation Pathways in COVID-19 Patients

ABSTRACT: The altered molecular proteins and pathways in response to COVID-19 infection are still unclear. Here, we performed a comprehensive proteomics-based investigation of of nasopharyngeal swab samples from COVID-19 patients to identify viral and host peptides by employing simple extraction strategies and also established a panel of host proteins using high-resolution mass spectrometry. The differentially expressed peptides/proteins identified from host and pathogen correlated with the viral load of the host which indicates that these proteins might be good prognostic biomarkers of severity prediction. A few host proteins such as Interleukin-6, L-lactate dehydrogenase, C-reactive protein, Ferritin and Aspartate aminotransferase was found to be upregulated in COVID-19 positive patients using targeted MRM study. Further, the proteins L-lactate dehydrogenase, Aspartate aminotransferase and Alanine aminotransferase was also validated in the clinical settings using immunological assays. We also identified neutrophil degranulation, platelet degranulation, interleukin-12 signaling pathways, mRNA translation of proteins and , co-factor metabolomic process protein metabolism, and stress responses to be key GO enriched pathways, thus altered in the COVID-19 infected patients.providing the detailed investigation of host response in COVID-19 infection , thus providing the landscape of COVID-19 pathophysiology. This study thus also revealed that mass spectrometry-based detected host proteins/peptides has a potential for clinical translation and a few proteins might be routinely monitored in clinics for the disease progression, peptide tests can be used by clinicians for diagnosis as well as identified pathways/ markers as the predictors of disease progression. Furthermore, the identified proteins and their drug binding studies might aid in COVID-19 therapeutic interventions.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Nasal Lavage Fluid

SUBMITTER: Avinash singh

LAB HEAD: Sanjeeva Srivastava

PROVIDER: PXD023016 | Pride | 2021-02-15

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	16112020_Fusion_Sample_S100.raw	Raw
	16112020_Fusion_Sample_S103.raw	Raw
	16112020_Fusion_Sample_S105.raw	Raw
	16112020_Fusion_Sample_S146.raw	Raw
	16112020_Fusion_Sample_S151.raw	Raw

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

Bankar Renuka R Suvarna Kruthi K Ghantasala Saicharan S Banerjee Arghya A Biswas Deeptarup D Choudhury Manisha M Palanivel Viswanthram V Salkar Akanksha A Verma Ayushi A Singh Avinash A Mukherjee Amrita A Pai Medha Gayathri J MGJ Roy Jyotirmoy J Srivastava Alisha A Badaya Apoorva A Agrawal Sachee S Shrivastav Om O Shastri Jayanthi J Srivastava Sanjeeva S

iScience 20210204 3

The altered molecular proteins and pathways in response to COVID-19 infection are still unclear. Here, we performed a comprehensive proteomics-based investigation of nasopharyngeal swab samples from patients with COVID-19 to study the host response by employing simple extraction strategies. Few of the host proteins such as interleukin-6, L-lactate dehydrogenase, C-reactive protein, Ferritin, and aspartate aminotransferase were found to be upregulated only in COVID-19-positive patients using targ ...[more]

PMID: 33558857

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Project description:COVID-19 is a pandemic that shares only certain clinical characteristics with other acute viral infections. Here, we studied the whole-blood transcriptomic host response to SARS-CoV-2 and compared it with other viral infections to understand similarities and differences in host response. We profiled peripheral blood from 24 healthy controls and 62 prospectively enrolled patients with community-acquired lower respiratory tract infection by SARS-Cov-2 within the first 24 hours of hospital admission using RNA-seq. We also collected 23 independent studies that profiled 1,855 blood samples from patients with one of six viruses (influenza, RSV, HRV, Ebola, Dengue, and SARS). We identified differentially expressed genes that change in patients with COVID-19 or other viral infections. We show changes in gene expression in peripheral blood from patients with COVID-19 are highly correlated with changes in response to other viral infections (r=0.74, p<0.001). However, two genes, ACO1 and ATL3, show significantly different changes in expression. Pathway analysis of differentially expressed genes in patients with COVID-19 or other viral infections versus healthy controls also identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection, and cytokine production for over-expressed genes, as well as lymphocyte differentiation and T cell activation for under-expressed genes. When comparing transcriptome profiles of patients with COVID-19 directly with those with other viral infections, we found 114 and 302 genes were over- and under-expressed, respectively during COVID-19. Pathways analysis did not identify any significant pathways in these genes. Statistical deconvolution using immunoStates found that M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells, and total B cells showed changes consistently in the same direction across all viral infections including COVID-19. Those that increased in COVID-19 but decreased in non-COVID were CD56bright NK cells, M2 macrophages, and total NK cells. The concordant and discordant responses mapped out via such a comparison provides a window to explore the underlying biology of why COVID-19 is so different from other viral infections encountered so far. Together, results from pathway and immunoStates analyses help dissect major shifts in cellularity and activation of signaling pathways as part of host response to SARS-CoV-2