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- Title
Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.
- Authors
Mann, Elizabeth R.; Menon, Madhvi; Knight, Sean Blandin; Konkel, Joanne E.; Jagger, Christopher; Shaw, Tovah N.; Krishnan, Siddharth; Rattray, Magnus; Ustianowski, Andrew; Bakerly, Nawar Diar; Dark, Paul; Lord, Graham M.; Simpson, Angela; Felton, Timothy; Ho, Ling-Pei; Feldmann, Marc; Grainger, John R.; Hussell, Tracy
- Abstract
Myeloid upheaval in severe COVID-19: Severe COVID-19 disease is associated with immune hyperactivation accompanied by "cytokine storm." Mann et al. used longitudinal analysis of fresh blood samples from hospitalized COVID-19 patients to search for biomarkers that signal impending progression to severe disease. Several phenotypic and functional abnormalities of CD14+ blood monocytes emerged as early-stage biomarkers predictive of increased severity of disease. Monocytes from patients with severe COVID-19 activated in vitro with lipopolysaccharide displayed increased proliferation and decreased expression of the prostaglandin-synthesizing cyclooxygenase-2 (COX-2) enzyme. Premature release of immature myeloid cells from the bone marrow contributes to innate immune dysfunction, causing more extensive lung damage and poorer clinical outcomes. These findings suggest that early treatment of COVID-19 targeting emergency myelopoiesis may help reduce the risk of subsequent clinical deterioration. 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.
- Publication
Science Immunology, 2020, Vol 5, Issue 51, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abd6197