Deep learning, 3D ultrastructural analysis reveals quantitative differences in platelet and organelle packing in COVID-19/SARSCoV2 patient-derived platelets.

Journal: Platelets
PMID: 37933490

Abstract

Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/mitochondrion-to-plateletvolume ratio is significantly greater in COVID-19 patient platelets indicating a denser packing of organelles, and a more compact platelet. The COVID-19 patient platelets were significantly smaller -by 35% in volume - with most of the difference in organelle packing density being due to decreased platelet size. There was little to no 3D ultrastructural evidence for differential activation of the platelets from COVID-19 patients. Though limited by sample size, our studies suggest that factors outside of the platelets themselves are likely responsible for COVID-19 complications. Our studies show how deep learning 3D methodology can become the gold standard for 3D ultrastructural studies of platelets.

Authors

  • Sagar S Matharu
    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
  • Cassidy S Nordmann
    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
  • Kurtis R Ottman
    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
  • Rahul Akkem
    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
  • Douglas Palumbo
    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
  • Denzel R D Cruz
    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
  • Kenneth Campbell
    Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Gail Sievert
    Center for Clinical Translational Science, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Jamie Sturgill
    Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA.
  • James Z Porterfield
    Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Smita Joshi
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Hammodah R Alfar
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Chi Peng
    State Key Laboratory of Petroleum Resource and Prospecting, China University of Petroleum-Beijing, Changping, Beijing, China.
  • Irina D Pokrovskaya
    University of Arkansas for Medical Sciences, Little Rock, 72205, USA.
  • Jeffrey A Kamykowski
    Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
  • Jeremy P Wood
    Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Beth Garvy
    Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Maria A Aronova
    National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, 20892, USA.
  • Sidney W Whiteheart
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA.
  • Richard D Leapman
    National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, 20892, USA.
  • Brian Storrie
    University of Arkansas for Medical Sciences, Little Rock, 72205, USA.

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