Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

Elizabeth R. Mann, Madhvi Menon, Sean Blandin Knight, Joanne E. Konkel, Christopher Jagger, Tovah N. Shaw, Siddharth Krishnan, Magnus Rattray, Andrew Ustianowski, Nawar Diar Bakerly, Paul Dark, Graham Lord, Angela Simpson, Timothy Felton, Ling-Pei Ho, Marc Feldmann, John R. Grainger, Tracy Hussell, Nicholas Scott, Alexander Mathioudakis

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Abstract

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells of hospitalized patients during the peak of the COVID-19 pandemic in the United Kingdom. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1, and IP-10 and modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, and enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of patients with COVID-19 and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission, suggesting that immunomodulating therapies would be most beneficial at early time points.
Original languageEnglish
Article numbereabd6197
JournalScience Immunology
Volume5
Issue number51
DOIs
Publication statusPublished - 18 Sept 2020

Keywords

  • Adult
  • Aged
  • Betacoronavirus/immunology
  • Biomarkers/blood
  • COVID-19
  • Coronavirus Infections/blood
  • Cyclooxygenase 2/immunology
  • Disease Progression
  • Female
  • Host Microbial Interactions/immunology
  • Humans
  • Immunity, Innate
  • Inflammation Mediators/blood
  • Ki-67 Antigen/immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Monocytes/immunology
  • Pandemics
  • Pneumonia, Viral/blood
  • Prospective Studies
  • SARS-CoV-2
  • Severity of Illness Index
  • United Kingdom/epidemiology

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