Assessing the potential correlation of polymorphisms in the IL6R with relative IL6 elevation in severely ill COVID-19 patients'.
Cytokine
; 148: 155662, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1330738
ABSTRACT
BACKGROUND:
Elevated Interleukin-6 (IL-6) may play an important role in the pathophysiology of COVID-19 yet attenuated response is not seen across all severe patients. We aimed to determine the effect of IL-6 baseline levels and other clinical variables on mortality and outcomes in hospitalized COVID-19 patients as well as to explore genetic variants associated with attenuated IL-6 response.METHODS:
Baseline IL-6 cytokine levels were measured in hospitalized patients participating in ongoing ODYSSEY phase 3 randomized study of tradipitant and placebo in hospitalized patients with severe COVID-19 who are receiving supplemental oxygen support. Furthermore blood samples for whole genome sequencing analysis were collected from 150 participants.RESULTS:
We report significantly elevated IL-6 in COVID-19 infected hospitalized patients, n = 100 (p-value < 0.0001) when compared to controls n = 324. We also report a significantly increased level of IL-6 (p-value < 0.01) between the severe and mild COVID-19 patients with severity defined on a WHO scale. Excessive IL-6 plasma levels correlate with higher mortality (p-value 0.001). Additionally, based on our classification analysis, combination of IL-6 elevation and high levels of serum glucose can identify highest risk-group of COVID19 patients. Furthermore, we explore the role of genetic regulatory variants affecting baseline IL-6 levels specifically in COVID-19 patients. We have directly tested the association between variants in the IL6 and IL6R gene region and IL6 plasma levels. We provide results for a common IL-6 variant previously associated with pneumonia, rs1800795, and rs2228145 that was previously shown to affect IL-6 plasma levels, as well as report on novel variants associated with IL-6 plasma levels detected in our study patients.CONCLUSIONS:
While it is unlikely that "cytokine storm" is the norm in severe COVID19, baseline elevations above 150 pg/ml may be associated with worst outcomes and as such may warrant treatment considerations. So far no clinical studies used IL-6 baseline assessment to stratify the patient population participating in clinical studies. We believe that careful examination and interpretation of the IL-6 levels and genetic variants can help to determine a patient population with a potentially very robust clinical response to IL-6 inhibition. TRIAL REGISTRATION Clinicaltrials.gov NCT04326426.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interleukin-6
/
Receptors, Interleukin-6
/
Polymorphism, Single Nucleotide
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Cytokine
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
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