Even bone marrow may not be a safe harbour from the ravages of COVID-19, according to a study that found previously unrecognised changes in newly produced immune cells, called monocytes, released into the blood from bone marrow.
To learn more about how the body responds to COVID-19, researchers at the University of Manchester, St Mary’s Hospital, Salford Royal NHS Foundation Trust, North Manchester General Hospital and the University of Oxford, obtained serial "snapshots" of patients' immune health by analysing their immune cells at multiple points during their hospital stays.
In COVID-19 patients with more severe disease, the monocytes do not function properly, researchers reported. It was not yet clear whether the monocytes are being released from the bone marrow in an altered state or whether the alterations happen after monocytes enter the blood, co-author Tracy Hussell of the University of Manchester in the UK is quoted as saying.
Either way, she said, treatments that prevent their release from the bone marrow may help reduce the exaggerated immune response that contributes to poor outcomes in patients with severe COVID-19.
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 (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. 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 most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as 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 COVID-19 patients 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 immune-modulating therapies would be most beneficial at early timepoints.
Authors
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, NIHR Respiratory TRC, Marc Feldmann, CIRCO, John R Grainger, Tracy Hussell
[link url="https://www.usnews.com/news/top-news/articles/2020-09-21/covid-19-may-damage-bone-marrow-immune-cells-another-reinfection-reported"]US News report[/link]
[link url="https://immunology.sciencemag.org/content/5/51/eabd6197"]Science Immunology abstract[/link]