Characterization of the inflammatory response to severe COVID-19 illness.pdf (853.86 kB)

Characterization of the inflammatory response to severe COVID-19 illness.

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posted on 23.02.2021, 10:56 by Oliver McElvaney, Natalie McEvoy, Oisín F McElvaney, Tomas Carroll, Mark Murphy, Danielle M Dunlea, Orna N Choileáin, Jennifer Clarke, Eoin O'Connor, Grace Hogan, Daniel Ryan, Imran Sulaiman, Cedric Gunaratnam, Peter Branagan, Michael E O'Brien, Ross Morgan, Richard Costello, Killian Hurley, Sean Walsh, Eoghan De Bara, Cora McNally, Samuel McConkey, Fiona Boland, Sinead Galvin, Fiona Kiernan, James O'Rourke, Rory Dwyer, Michael Power, Pierce Geoghegan, Caroline Larkin, Ruth A O'Leary, James Freeman, Alan Gaffney, Brian Marsh, Gerard Curley, Noel G McElvaney

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.

Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.

Methods: Levels of IL-1β, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.

Measurements and Main Results: IL-1β, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).

Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Measurements and Main Results: IL-1β, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).

Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Funding

Elaine Galwey Memorial Research Bursary

American Thoracic Society ATS International Trainee Scholarship Award

American Thoracic Society ATS Abstract Scholarship Award

History

Comments

The original article is available at https://www.atsjournals.org/

Published Citation

McElvaney OJ, McEvoy NL, McElvaney OF, Carroll TP, Murphy MP, Dunlea DM, Ní Choileáin O, Clarke J, O'Connor E, Hogan G, Ryan D, Sulaiman I, Gunaratnam C, Branagan P, O'Brien ME, Morgan RK, Costello RW, Hurley K, Walsh S, de Barra E, McNally C, McConkey S, Boland F, Galvin S, Kiernan F, O'Rourke J, Dwyer R, Power M, Geoghegan P, Larkin C, O'Leary RA, Freeman J, Gaffney A, Marsh B, Curley GF, McElvaney NG. Characterization of the inflammatory response to severe COVID-19 illness. American Journal of Respiratory and Critical Care Medicine. 2020;202(6):812-821.

Publication Date

15 September 2020

PubMed ID

32584597

Department/Unit

  • Beaumont Hospital
  • Medicine
  • Data Science Centre
  • International Health and Tropical Medicine
  • Anaesthetics and Critical Care

Research Area

  • Respiratory Medicine
  • Population Health and Health Services
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

American Thoracic Society

Version

  • Published Version (Version of Record)