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Schurink B, Roos E, Radonic T, et al. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe. 2020;1(7):e290-e299doi: 10.1016/S2666-5247(20)30144-0.
Schurink, B., Roos, E., Radonic, T., Barbe, E., Bouman, C. S. C., de Boer, H. H., de Bree, G. J., Bulle, E. B., Aronica, E. M., Florquin, S., Fronczek, J., Heunks, L. M. A., de Jong, M. D., Guo, L., du Long, R., Lutter, R., Molenaar, P. C. G., Neefjes-Borst, E. A., Niessen, H. W. M., van Noesel, C. J. M., Roelofs, J. J. T. H., Snijder, E. J., Soer, E. C., Verheij, J., Vlaar, A. P. J., Vos, W., van der Wel, N. N., van der Wal, A. C., van der Valk, P., & Bugiani, M. (2020). Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. The Lancet. Microbe, 1(7), e290-e299. https://doi.org/10.1016/S2666-5247(20)30144-0
Schurink, Bernadette, et al. "Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study." The Lancet. Microbe vol. 1,7 (2020): e290-e299. doi: https://doi.org/10.1016/S2666-5247(20)30144-0
Schurink B, Roos E, Radonic T, Barbe E, Bouman CSC, de Boer HH, de Bree GJ, Bulle EB, Aronica EM, Florquin S, Fronczek J, Heunks LMA, de Jong MD, Guo L, du Long R, Lutter R, Molenaar PCG, Neefjes-Borst EA, Niessen HWM, van Noesel CJM, Roelofs JJTH, Snijder EJ, Soer EC, Verheij J, Vlaar APJ, Vos W, van der Wel NN, van der Wal AC, van der Valk P, Bugiani M. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe. 2020 Nov;1(7):e290-e299. doi: 10.1016/S2666-5247(20)30144-0. Epub 2020 Sep 25. PMID: 33015653; PMCID: PMC7518879.
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Lancet Microbe. 2020 Nov;1(7):e290-e299. doi: 10.1016/S2666-5247(20)30144-0. Epub 2020 Sep 25.

Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study.

The Lancet. Microbe

Bernadette Schurink, Eva Roos, Teodora Radonic, Ellis Barbe, Catherine S C Bouman, Hans H de Boer, Godelieve J de Bree, Esther B Bulle, Eleonora M Aronica, Sandrine Florquin, Judith Fronczek, Leo M A Heunks, Menno D de Jong, Lihui Guo, Romy du Long, Rene Lutter, Pam C G Molenaar, E Andra Neefjes-Borst, Hans W M Niessen, Carel J M van Noesel, Joris J T H Roelofs, Eric J Snijder, Eline C Soer, Joanne Verheij, Alexander P J Vlaar, Wim Vos, Nicole N van der Wel, Allard C van der Wal, Paul van der Valk, Marianna Bugiani

Affiliations

  1. Department of Pathology, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, Netherlands.
  2. Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  3. Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  4. Department of Forensic Medicine, Netherlands Forensic Institute, The Hague, Netherlands.
  5. Department of Internal Medicine, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  6. Department of Intensive Care Medicine, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, Netherlands.
  7. Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  8. Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  9. Department of Pulmonary Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  10. Department of Cardiac Surgery, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, Netherlands.
  11. Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
  12. Electron Microscopy Center Amsterdam, Department of Medical Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

PMID: 33015653 PMCID: PMC7518879 DOI: 10.1016/S2666-5247(20)30144-0

Abstract

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy.

METHODS: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course.

FINDINGS: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets..

INTERPRETATION: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19.

FUNDING: Amsterdam UMC Corona Research Fund.

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

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