Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19
OBJECTIVES:. 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 Un...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2022-12-01
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| Series: | Critical Care Explorations |
| Online Access: | http://journals.lww.com/10.1097/CCE.0000000000000813 |
| _version_ | 1828086660759289856 |
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| author | F. Linzee Mabrey, MD Pavan K. Bhatraju, MD, MSc Eric D. Morrell, MD Leila R. Zelnick, PhD Neha A. Sathe, MD Nicholas G. O’Connor, BS Carmen Mikacenic, MD Thomas R. Martin, MD W. Conrad Liles, MD, PhD Mark M. Wurfel, MD, PhD |
| author_facet | F. Linzee Mabrey, MD Pavan K. Bhatraju, MD, MSc Eric D. Morrell, MD Leila R. Zelnick, PhD Neha A. Sathe, MD Nicholas G. O’Connor, BS Carmen Mikacenic, MD Thomas R. Martin, MD W. Conrad Liles, MD, PhD Mark M. Wurfel, MD, PhD |
| author_sort | F. Linzee Mabrey, MD |
| collection | DOAJ |
| description | OBJECTIVES:. 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. |
| first_indexed | 2024-04-11T04:58:48Z |
| format | Article |
| id | doaj.art-702f096281464ae990290eca015e72e5 |
| institution | Directory Open Access Journal |
| issn | 2639-8028 |
| language | English |
| last_indexed | 2024-04-11T04:58:48Z |
| publishDate | 2022-12-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Critical Care Explorations |
| spelling | doaj.art-702f096281464ae990290eca015e72e52022-12-26T06:01:07ZengWolters KluwerCritical Care Explorations2639-80282022-12-01412e081310.1097/CCE.0000000000000813202212000-00020Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19F. Linzee Mabrey, MD0Pavan K. Bhatraju, MD, MSc1Eric D. Morrell, MD2Leila R. Zelnick, PhD3Neha A. Sathe, MD4Nicholas G. O’Connor, BS5Carmen Mikacenic, MD6Thomas R. Martin, MD7W. Conrad Liles, MD, PhD8Mark M. Wurfel, MD, PhD91 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.3 Kidney Research Institute (KRI), Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.OBJECTIVES:. 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.http://journals.lww.com/10.1097/CCE.0000000000000813 |
| spellingShingle | F. Linzee Mabrey, MD Pavan K. Bhatraju, MD, MSc Eric D. Morrell, MD Leila R. Zelnick, PhD Neha A. Sathe, MD Nicholas G. O’Connor, BS Carmen Mikacenic, MD Thomas R. Martin, MD W. Conrad Liles, MD, PhD Mark M. Wurfel, MD, PhD Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19 Critical Care Explorations |
| title | Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19 |
| title_full | Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19 |
| title_fullStr | Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19 |
| title_full_unstemmed | Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19 |
| title_short | Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19 |
| title_sort | plasma interleukin 6 predicts clinical decline after completion of dexamethasone therapy in severe covid 19 |
| url | http://journals.lww.com/10.1097/CCE.0000000000000813 |
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