ObjectivesSevere 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.MethodsAdult 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.ResultsA 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.ConclusionsThe 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.
Introduction
Glomerular filtration rate (GFR) is routinely estimated with cystatin C. In June 2010, the International Federation of Clinical Chemistry (IFCC) released a certified cystatin C reference material (ERM-DA471/IFCC), and new cystatin C glomerular filtration rate estimation (eGFR) equations were developed with the IFCC standard. Early in 2018, Siemens discontinued their nonstandardized cystatin C reagent kits and replaced them with IFCC-calibrated kits in the US market. The aim of the current study was to assess the effect of IFCC calibration on cystatin C values and corresponding GFR estimations.
Methods
Cystatin C concentration was measured in 81 pediatric patients using a plasma sample from their nuclear GFR measurement with 99mTc-diethylenetriaminepentaaccetic acid. Calibration curves were generated using Siemens nonstandardized and IFCC-standardized kits to measure paired cystatin C concentrations in each sample. GFR-estimating equations using pre-IFCC and IFCC cystatin C values were compared using Bland-Altman analyses.
Results
The IFCC-standardized assay resulted in a mean increase in the measured cystatin C value of 24%. Estimating equations consistently overestimated GFR prior to IFCC standardization. Following incorporation of the IFCC standard, the Full Age Spectrum equation demonstrated the best overall performance, whereas the Chronic Kidney Disease in Children (CKiD) equation was more accurate in children with decreased GFR.
Conclusion
Incorporation of the IFCC standard significantly increased cystatin C values and affected the performance of GFR estimating equations. Clinical laboratories and providers may need to update the equation used for cystatin C–based estimation of GFR following adoption of the IFCC reference standard.
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