Characterization of the Inflammatory Response to Severe COVID-19 Illness.
Am J Respir Crit Care Med
; 202(6): 812-821, 2020 09 15.
Article
in English
| MEDLINE | ID: covidwho-614625
ABSTRACT
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-1ß, 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 MainResults:
IL-1ß, 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-1ß, 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-6AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6AAT 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Thyroid Hormones
/
Carrier Proteins
/
Alpha 1-Antitrypsin
/
Cytokines
/
Acute-Phase Reaction
/
Coronavirus Infections
/
Lactic Acid
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
Membrane Proteins
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
Language:
English
Journal:
Am J Respir Crit Care Med
Journal subject:
Critical Care
Year:
2020
Document Type:
Article
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