Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19

F Linzee Mabrey; Pavan K Bhatraju; Eric D Morrell; Leila R Zelnick; Neha A Sathe; Nicholas G O'Connor; Carmen Mikacenic; Thomas R Martin; W Conrad Liles; Mark M Wurfel

doi:10.1097/CCE.0000000000000813

Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19

Crit Care Explor. 2022 Dec 14;4(12):e0813. doi: 10.1097/CCE.0000000000000813. eCollection 2022 Dec.

Authors

F Linzee Mabrey^{1

2}, Pavan K Bhatraju^{1

2}, Eric D Morrell^{1

2}, Leila R Zelnick³, Neha A Sathe^{1

2}, Nicholas G O'Connor¹, Carmen Mikacenic^{1

2

4}, Thomas R Martin¹, W Conrad Liles^{1

2}, Mark M Wurfel^{1

2}

Affiliations

¹ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.
² Sepsis Center of Research Excellence-UW (SCORE-UW), University of Washington, Seattle, WA.
³ Kidney Research Institute (KRI), Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA.
⁴ Translational Research, Benaroya Research Institute, Seattle, WA.

Abstract

To identify and characterize clinical decline after completion of dexamethasone in severe COVID-19 and determine whether interleukin (IL)-6 and other inflammatory biomarkers predict the occurrence of clinical decline.

Design: Prospective observational cohort.

Setting: ICUs in three University of Washington affiliated hospitals between July 2020 and April 2021.

Patients: Patients admitted to an ICU with COVID-19 who completed a course of dexamethasone.

Measurements and main results: We identified 65 adult patients with severe COVID-19 who completed a 10-day course of dexamethasone, of whom 60 had plasma samples collected within 3 days of dexamethasone completion. We measured IL-6 with a clinical-grade electrochemiluminescent assay and a larger panel of inflammatory biomarkers (IL-8, Monocyte Chemoattractant Protein-1, Monocyte Inflammatory Protein-1 alpha, interferon gamma, C-X-C Motif Chemokine Ligand 10, WBC, bicarbonate) with a research immunoassay. We defined clinical decline by the occurrence of incident severe kidney injury, incident or escalating shock or fever, worsening hypoxemia, or death within 5 days of completion of dexamethasone. We estimated risk for clinical decline by standardized log₂ transformed biomarker concentration using multivariable logistic regression. Clinical decline post-dexamethasone was common, occurring in 49% of patients (n = 32). Among all biomarkers, IL-6 levels were most strongly associated with clinical decline. After adjustment for age, sex, and study site, the odds of post-dexamethasone clinical decline were 7.33 times higher per one sd increase in log2 transformed IL-6 concentrations (adjusted odds ratio, 7.33; CI, 2.62-20.47; p < 0.001). The discriminatory power of IL-6 for clinical decline was high (cross-validated mean area under the receiver operating characteristic curve, 0.90; 95% CI, 0.79-0.95).

Conclusions: Clinical decline after completion of dexamethasone for severe COVID-19 is common. IL-6 concentrations obtained prior to completion of dexamethasone may have utility in identifying those at highest risk for subsequent worsening. If validated, future work might test whether plasma IL-6 could be used as a tool for a personalized approach to duration of dexamethasone treatment in severe COVID-19.

Keywords: COVID-19; dexamethasone; interleukin-6; post-dexamethasone clinical decline.

Abstract

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