panorama0000ProteomicsSanjeeva SrivastavaHomo Sapienshttps://panoramaweb.org/longitudinal_plasma_MRM.urlsanjeeva@iitb.ac.inBiosciences and Bioengineering Department, IIT BombayPanoramaPublicSevere 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.A Multi-omics Longitudinal Study Reveals Alteration of the Leukocyte Activation Pathway in COVID-19 Patients.Suvarna Kruthi K, Salkar Akanksha A, Palanivel Viswanthram V, Bankar Renuka R, Banerjee Nirjhar N, Gayathri J Pai Medha M, Srivastava Alisha A, Singh Avinash A, Khatri Harsh H, Agrawal Sachee S, Shrivastav Om O, Shastri Jayanthi J, Srivastava Sanjeeva SFresh, PROFILIN 1, other disease, Frozen Plasma, Fresh Frozen Plasma, Effects, protein complex, Blood, Proteins, disorders, Longterm Effect, total expressed protein, Gene, medical condition, protein, protein-containing complex, Plasmas, Client, Profilin, Long Term, Multiple Reaction Monitoring, Frozen Plasmas, F6F22_21, native protein, diseases, Profilin Proteins, Profilin-1., Long Term Effects, Protein, Diseases, Gene Products, disease or disorder, condition, diseases and disorders, protein aggregate, F6F22.21, Effect, PFN1, Plasma, study, Fresh Frozen Plasmas, Fresh Frozen, Blood Plasma, human disease, cholecalciferol binding, Profilin 1, MRM, Profilin 2, Longterm, Profilin 3, calciferol binding, Profilin 4, portion of plasma, patient, Long-Term, free, Longterm Effects, non-neoplastic, Protein Gene Products, Gene Proteins, disease, Patient, label, Clients, Blood Plasmas, Profilin I, disorder, Profilin-4, Homo sapiens disease, Long-Term Effect, ergocalciferol binding, Proteomes, Long-Term Effects, profilin 1, plasma, Profilin-2, Profilin-3Panomics, COVID19, Disease, Integrative-Omics, Coronavirus Disease 19, β-CoV, beta-CoV, COVID-19, SARS-CoV-2, Virus Infection, COVID-19 Virus Diseases, 2019 novel coronavirus, leucocyte activation, 2019 Novel Coronavirus Disease, SARS-CoV-2 Infections, 2019 nCoV Infection, Integrative Omics, COVID 19 Virus Infection, Virus Disease, 2019 nCoV Disease, Multi-Omics, COVID-19 Virus Disease, 2019-nCoV Infection, Client., 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mass spectroscopy, deceased, determination, Blood, positive regulation by symbiont of host non-apoptotic programmed cell death, Infestations and Infections, Virus Infection, 2019 novel coronavirus, Cardiac Death, End-Of-Life, Virus Disease, thrombocyte aggregation, 2019 nCoV Disease, Long Term, element, Polypeptides, primary metabolites, peptido, Roles, 2019-nCoV Disease, Concepts, pathogenesis, cytokine secretion, Effect, COVID 19 Pandemic, WMS, organ, E-Cigarette or Vaping Product Use-Associated Lung Injury, Fresh Frozen Plasmas, Fresh Frozen, Immune Processes, Immune Responses, LCMSMS, peptides, stimulation by symbiont of host programmed cell death, Coronavirus Disease 2019, End Of Life, Coronavirus Disease-19, elevated, beta-CoVs, Lung Injury, free, Immune, scientific observation, interleukin secretion, Role Concepts, Therapies, Infections and Infestations, GPHYSD2, COVID 19 Virus Disease, Long-Term Effects, plasma, EVALIs, SGS, 2019-nCoV Infections, LC-MS2, Therapy, Frozen Plasma, 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disfunctional, Complement Protein, presence, LC-MS-MS, E Cigarette Use Associated Lung Injury, Cardiac, Vaping Product Use Associated Lung Injury, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, ECTOL1, LC-MSMS, SARS CoV 2 Infection, Gene Products, Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Chronic Lung Injuries, E Cigarette or Vaping Product Use Associated Lung Injury, β-coronavirus, 2019-nCoV, Pulmonary, Blood Plasma, β-CoVs, Injury, MRM, Longterm, COVID-19 Virus Infection, Aggregation, severe acute respiratory syndrome coronavirus 2, Treatments., causes, Long-Term, SARS-CoV-2 Infection, arginine metabolism, clinical infection, interferon secretion, OCTD, COVID-19 Virus, Infestation and Infection, Immune Response, anatomical unit, Blood Plasmas, body organ, causality, Vaping Product Use-Associated Lung Injury, Chronic, peptidos, Hemolytic, immune cell activation, Long-Term Effect, Immune Process, high elevation, SARS Coronavirus 2 Infection, measuring, Disease, Coronavirus Disease 19, activation by organism of non-apoptotic programmed cell death in other organism, beta-CoV, hemolysin activity, Proteins, Chronic Lung Injury, cytokine metabolic process, defective, SARS-CoV-2 Infections, leucocyte activation, Peptide, Concept, COVID-19 Virus Disease, 2019-nCoV Infection, Frozen Plasmas, count in organism, LC/MS/MS, Cytokine, chemical analysis, Long Term Effects, Protein, post-mortem, proteomic analysis, Infection, MFS1, Hemolytic Complement, Death, WMS2, Plasma, death, betacoronavirus, Disease 2019, distinct, Pulmonary Injuries, metabolite, portion of plasma, COVID-19 Pandemics, COVID-19 Pandemic, SARS-coronavirus 2, Injuries, Longterm Effects, Protein Gene Products, cytokine biosynthetic process, Gene Proteins, Complement Proteins, Therapeutic, SSKS, Response, liquid chromatography tandem mass spectrometry, Peptid, Treatment, assay, Severe, COVID 190falseValidation of proteins showing significant dysregulation from shotgun proteomics experiments in longitudinal plasma samples of COVID-19 patientsA Label Free Quantification study was done to observe the changes in the plasma proteome of patient samples collected at two different time points of disease severity (T1 and T2). A few of the proteins that were significantly dysregulated between the two time points were taken forward for validation using the Multiple Reaction Monitoring approach. The Skyline file here shows two proteins: 10 Vitamin D binding protein and Profilin 1.Mon Jun 27 00:00:00 GMT+01:00 2022PXD026848960634379420