Frontiers in Immunology (Oct 2021)

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

  • Jafar Sarif,
  • Jafar Sarif,
  • Deblina Raychaudhuri,
  • Ranit D’Rozario,
  • Ranit D’Rozario,
  • Purbita Bandopadhyay,
  • Purbita Bandopadhyay,
  • Praveen Singh,
  • Praveen Singh,
  • Priyanka Mehta,
  • Md. Asmaul Hoque,
  • Md. Asmaul Hoque,
  • Bishnu Prasad Sinha,
  • Bishnu Prasad Sinha,
  • Manoj Kushwaha,
  • Shweta Sahni,
  • Priti Devi,
  • Priti Devi,
  • Partha Chattopadhyay,
  • Partha Chattopadhyay,
  • Shekhar Ranjan Paul,
  • Yogiraj Ray,
  • Yogiraj Ray,
  • Kausik Chaudhuri,
  • Sayantan Banerjee,
  • Debajyoti Majumdar,
  • Debajyoti Majumdar,
  • Bibhuti Saha,
  • Biswanath Sharma Sarkar,
  • Prasun Bhattacharya,
  • Shilpak Chatterjee,
  • Sandip Paul,
  • Pramit Ghosh,
  • Rajesh Pandey,
  • Rajesh Pandey,
  • Shantanu Sengupta,
  • Shantanu Sengupta,
  • Dipyaman Ganguly,
  • Dipyaman Ganguly

DOI
https://doi.org/10.3389/fimmu.2021.738093
Journal volume & issue
Vol. 12

Abstract

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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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