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The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19).
Henry, Brandon Michael; Benoit, Stefanie W; Vikse, Jens; Berger, Brandon A; Pulvino, Christina; Hoehn, Jonathan; Rose, James; Santos de Oliveira, Maria Helena; Lippi, Giuseppe; Benoit, Justin L.
  • Henry BM; Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Benoit SW; Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Vikse J; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Berger BA; Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway.
  • Pulvino C; Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Hoehn J; Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Rose J; Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Santos de Oliveira MH; Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Lippi G; Department of Statistics, Federal University of Parana, Curitiba, Brazil.
  • Benoit JL; Department of Neuroscience, Biomedicine and Movement, Section of Clinical Biochemistry, University of Verona, Verona, Italy.
Clin Chem Lab Med ; 59(3): 599-607, 2021 02 23.
Article in English | MEDLINE | ID: covidwho-1067439
Semantic information from SemMedBD (by NLM)
1. interleukin-10 ASSOCIATED_WITH COVID-19
Subject
interleukin-10
Predicate
ASSOCIATED_WITH
Object
COVID-19
2. Immune status AFFECTS COVID-19
Subject
Immune status
Predicate
AFFECTS
Object
COVID-19
3. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
4. Severe disease PROCESS_OF Patients
Subject
Severe disease
Predicate
PROCESS_OF
Object
Patients
5. Patients LOCATION_OF interleukin-10
Subject
Patients
Predicate
LOCATION_OF
Object
interleukin-10
6. interleukin-6 STIMULATES interleukin-10
Subject
interleukin-6
Predicate
STIMULATES
Object
interleukin-10
7. interleukin-8 STIMULATES interleukin-10
Subject
interleukin-8
Predicate
STIMULATES
Object
interleukin-10
8. interleukin-10 PREDISPOSES COVID-19
Subject
interleukin-10
Predicate
PREDISPOSES
Object
COVID-19
9. negative regulation of inflammatory response ASSOCIATED_WITH COVID-19
Subject
negative regulation of inflammatory response
Predicate
ASSOCIATED_WITH
Object
COVID-19
10. interleukin-10 ASSOCIATED_WITH COVID-19
Subject
interleukin-10
Predicate
ASSOCIATED_WITH
Object
COVID-19
11. Immune status AFFECTS COVID-19
Subject
Immune status
Predicate
AFFECTS
Object
COVID-19
12. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
13. Severe disease PROCESS_OF Patients
Subject
Severe disease
Predicate
PROCESS_OF
Object
Patients
14. Patients LOCATION_OF interleukin-10
Subject
Patients
Predicate
LOCATION_OF
Object
interleukin-10
15. interleukin-6 STIMULATES interleukin-10
Subject
interleukin-6
Predicate
STIMULATES
Object
interleukin-10
16. interleukin-8 STIMULATES interleukin-10
Subject
interleukin-8
Predicate
STIMULATES
Object
interleukin-10
17. interleukin-10 PREDISPOSES COVID-19
Subject
interleukin-10
Predicate
PREDISPOSES
Object
COVID-19
18. negative regulation of inflammatory response ASSOCIATED_WITH COVID-19
Subject
negative regulation of inflammatory response
Predicate
ASSOCIATED_WITH
Object
COVID-19
ABSTRACT

OBJECTIVES:

Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes.

METHODS:

Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit.

RESULTS:

A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8.

CONCLUSIONS:

The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Interleukin-10 / COVID-19 Subject: Interleukin-10 / COVID-19 Type of study: Diagnostic study / Etiology study / Incidence study / Observational study / Prognostic study / Risk factors Language: English Journal: Clin Chem Lab Med Clinical aspect: Diagnosis / Etiology / Prediction / Prognosis Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Interleukin-10 / COVID-19 Subject: Interleukin-10 / COVID-19 Type of study: Diagnostic study / Etiology study / Incidence study / Observational study / Prognostic study / Risk factors Language: English Journal: Clin Chem Lab Med Clinical aspect: Diagnosis / Etiology / Prediction / Prognosis Year: 2021
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