2 research outputs found
Corrigendum to 'A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19'
The authors wish to correct a typographical error in the
manuscript. In both the abstract and Section 3.4 of the original manuscript, a
1-point increase in the Dublin-Boston score was described as being associated
with a 5.6 times increased odds (OR 5.62, 95% CI = 3.229.81, P = 1.2 ÂŁ 109 )
for a more severe outcome. While the OR and P-value stated are correct, the CI
should instead have read “3.229.81”. The CI listed in Table 3 of the original
manuscript, which accompanied Section 3.4, is correct. The authors regret any
confusion caused, and appreciate the opportunity to correct this mistake.</div
Characterization of the inflammatory response to severe COVID-19 illness.
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
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
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.</p