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Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19.
Sarif, Jafar; Raychaudhuri, Deblina; D'Rozario, Ranit; Bandopadhyay, Purbita; Singh, Praveen; Mehta, Priyanka; Hoque, Md Asmaul; Sinha, Bishnu Prasad; Kushwaha, Manoj; Sahni, Shweta; Devi, Priti; Chattopadhyay, Partha; Paul, Shekhar Ranjan; Ray, Yogiraj; Chaudhuri, Kausik; Banerjee, Sayantan; Majumdar, Debajyoti; Saha, Bibhuti; Sarkar, Biswanath Sharma; Bhattacharya, Prasun; Chatterjee, Shilpak; Paul, Sandip; Ghosh, Pramit; Pandey, Rajesh; Sengupta, Shantanu; Ganguly, Dipyaman.
  • Sarif J; Indian Institute of Chemical Biology (IICB)-Translational Research Unit of Excellence, Council of Scientific & Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India.
  • Raychaudhuri D; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • D'Rozario R; Indian Institute of Chemical Biology (IICB)-Translational Research Unit of Excellence, Council of Scientific & Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India.
  • Bandopadhyay P; Indian Institute of Chemical Biology (IICB)-Translational Research Unit of Excellence, Council of Scientific & Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India.
  • Singh P; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Mehta P; Indian Institute of Chemical Biology (IICB)-Translational Research Unit of Excellence, Council of Scientific & Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India.
  • Hoque MA; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Sinha BP; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Kushwaha M; Cardiorespiratory Disease Biology, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, New Delhi, India.
  • Sahni S; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, New Delhi, India.
  • Devi P; Indian Institute of Chemical Biology (IICB)-Translational Research Unit of Excellence, Council of Scientific & Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India.
  • Chattopadhyay P; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Paul SR; Indian Institute of Chemical Biology (IICB)-Translational Research Unit of Excellence, Council of Scientific & Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India.
  • Ray Y; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Chaudhuri K; Cardiorespiratory Disease Biology, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, New Delhi, India.
  • Banerjee S; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, New Delhi, India.
  • Majumdar D; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Saha B; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, New Delhi, India.
  • Sarkar BS; Department of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Bhattacharya P; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, New Delhi, India.
  • Chatterjee S; Department of Medicine, Infectious Diseases and Beliaghata General (ID & BG) Hospital, Kolkata, India.
  • Paul S; Department of Medicine, Infectious Diseases and Beliaghata General (ID & BG) Hospital, Kolkata, India.
  • Ghosh P; Department of Tropical Medicine, School of Tropical Medicine, Kolkata, India.
  • Pandey R; Department of Medicine, Infectious Diseases and Beliaghata General (ID & BG) Hospital, Kolkata, India.
  • Sengupta S; Department of Medicine, Infectious Diseases and Beliaghata General (ID & BG) Hospital, Kolkata, India.
  • Ganguly D; Department of Medicine, Infectious Diseases and Beliaghata General (ID & BG) Hospital, Kolkata, India.
Front Immunol ; 12: 738093, 2021.
Article in English | MEDLINE | ID: covidwho-1518484
Preprint
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ABSTRACT
Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. Flow cytometry and next-generation sequencing were done on peripheral blood cells and urokinase-type plasminogen activator receptor (suPAR), and cytokines were measured from and mass spectrometry-based proteomics was done on plasma samples from an Indian cohort of COVID-19 patients. Publicly available single-cell RNA sequencing data were analyzed for validation of primary data. Statistical analyses were performed to validate risk stratification. We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio 2.9286, 95% confidence interval 1.0427-8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcomes, in terms of both survival benefit (hazard ratio 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus, we identified suPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Urokinase Plasminogen Activator / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Humans / Middle aged / Young adult Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.738093

Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Urokinase Plasminogen Activator / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Humans / Middle aged / Young adult Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.738093