tetano
Editor, Senior Moderator
Am J Respir Crit Care Med
. 2020 Jun 25.
doi: 10.1164/rccm.202005-1583OC. Online ahead of print.
Characterization of the Inflammatory Response to Severe COVID-19 Illness
Oliver J McElvaney[SUP] 1 [/SUP], Natalie McEvoy[SUP] 1 [/SUP], Ois?n F McElvaney[SUP] 1 [/SUP], Tom?s P Carroll[SUP] 2 [/SUP], Mark P Murphy[SUP] 1 [/SUP], Danielle M Dunlea[SUP] 1 [/SUP], Orna N? Choile?in[SUP] 3 [/SUP], Jennifer Clarke[SUP] 1 [/SUP], Eoin O'Connor[SUP] 3 [/SUP], Grace Hogan[SUP] 1 [/SUP], Daniel Ryan[SUP] 1 [/SUP], Imran Sulaiman[SUP] 3 [/SUP], Cedric Gunaratnam[SUP] 4 [/SUP], Peter Branagan[SUP] 3 [/SUP], Michael E O'Brien[SUP] 3 [/SUP], Ross K Morgan[SUP] 5 [/SUP], Richard W Costello[SUP] 6 [/SUP], Killian Hurley[SUP] 7 [/SUP], Se?n Walsh[SUP] 3 [/SUP], Eoghan de Barra[SUP] 3 [/SUP], Cora McNally[SUP] 3 [/SUP], Samuel McConkey[SUP] 3 [/SUP], Fiona Boland[SUP] 8 [/SUP], Sinead Galvin[SUP] 3 [/SUP], Fiona Kiernan[SUP] 3 [/SUP], James O'Rourke[SUP] 3 [/SUP], Rory Dwyer[SUP] 3 [/SUP], Michael Power[SUP] 3 [/SUP], Pierce Geoghegan[SUP] 3 [/SUP], Caroline Larkin[SUP] 3 [/SUP], Ruth Aoibheann O'Leary[SUP] 3 [/SUP], James Freeman[SUP] 3 [/SUP], Alan Gaffney[SUP] 3 [/SUP], Brian Marsh[SUP] 9 [/SUP], Gerard F Curley[SUP] 10 [/SUP], Noel G McElvaney[SUP] 11 [/SUP]
Affiliations
Abstract
Rationale: Coronavirus disease 2019 (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 interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1) were assessed in plasma from healthy volunteers, hospitalized-but-stable COVID-19 patients (COVIDstable), COVID-19 patients requiring intensive care unit (ICU) admission (COVIDICU) and individuals with severe community-acquired pneumonia requiring ICU support (CAPICU). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of alpha-1 antitrypsin (AAT) to COVID-19 was also evaluated.
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, and demonstrated higher levels of IL-1β, IL-6 and sTNFR1 - but lower IL-10 - than CAPICU. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2, phosphorylated PKM2, HIF-1α and lactate. The production and sialylation of AAT increased in COVID-19, but this anti-inflammatory 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 COVID-19 patients, increases in IL-6:AAT predicted prolonged ICU stay and mortality, while 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
. 2020 Jun 25.
doi: 10.1164/rccm.202005-1583OC. Online ahead of print.
Characterization of the Inflammatory Response to Severe COVID-19 Illness
Oliver J McElvaney[SUP] 1 [/SUP], Natalie McEvoy[SUP] 1 [/SUP], Ois?n F McElvaney[SUP] 1 [/SUP], Tom?s P Carroll[SUP] 2 [/SUP], Mark P Murphy[SUP] 1 [/SUP], Danielle M Dunlea[SUP] 1 [/SUP], Orna N? Choile?in[SUP] 3 [/SUP], Jennifer Clarke[SUP] 1 [/SUP], Eoin O'Connor[SUP] 3 [/SUP], Grace Hogan[SUP] 1 [/SUP], Daniel Ryan[SUP] 1 [/SUP], Imran Sulaiman[SUP] 3 [/SUP], Cedric Gunaratnam[SUP] 4 [/SUP], Peter Branagan[SUP] 3 [/SUP], Michael E O'Brien[SUP] 3 [/SUP], Ross K Morgan[SUP] 5 [/SUP], Richard W Costello[SUP] 6 [/SUP], Killian Hurley[SUP] 7 [/SUP], Se?n Walsh[SUP] 3 [/SUP], Eoghan de Barra[SUP] 3 [/SUP], Cora McNally[SUP] 3 [/SUP], Samuel McConkey[SUP] 3 [/SUP], Fiona Boland[SUP] 8 [/SUP], Sinead Galvin[SUP] 3 [/SUP], Fiona Kiernan[SUP] 3 [/SUP], James O'Rourke[SUP] 3 [/SUP], Rory Dwyer[SUP] 3 [/SUP], Michael Power[SUP] 3 [/SUP], Pierce Geoghegan[SUP] 3 [/SUP], Caroline Larkin[SUP] 3 [/SUP], Ruth Aoibheann O'Leary[SUP] 3 [/SUP], James Freeman[SUP] 3 [/SUP], Alan Gaffney[SUP] 3 [/SUP], Brian Marsh[SUP] 9 [/SUP], Gerard F Curley[SUP] 10 [/SUP], Noel G McElvaney[SUP] 11 [/SUP]
Affiliations
- PMID: 32584597
- DOI: 10.1164/rccm.202005-1583OC
Abstract
Rationale: Coronavirus disease 2019 (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 interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1) were assessed in plasma from healthy volunteers, hospitalized-but-stable COVID-19 patients (COVIDstable), COVID-19 patients requiring intensive care unit (ICU) admission (COVIDICU) and individuals with severe community-acquired pneumonia requiring ICU support (CAPICU). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of alpha-1 antitrypsin (AAT) to COVID-19 was also evaluated.
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, and demonstrated higher levels of IL-1β, IL-6 and sTNFR1 - but lower IL-10 - than CAPICU. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2, phosphorylated PKM2, HIF-1α and lactate. The production and sialylation of AAT increased in COVID-19, but this anti-inflammatory 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 COVID-19 patients, increases in IL-6:AAT predicted prolonged ICU stay and mortality, while 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).