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Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19.
J Clin Immunol. 2021 05; 41(4):738-747.JC

Abstract

We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical SARS-CoV-2 infection. Disease severity was based on maximum oxygen requirement during hospital stay to maintain SpO2 > 93% (moderate, 0-3 L NC; severe, 4-6 L NC or non-rebreather; critical, HFNC, NIPPV, or MV). All patients were treated using the institution's treatment algorithm, which included consideration of tocilizumab for severe and critical disease. The most common cytokine elevations among all patients included IL-6, sIL2R, IFN-γ, and IL-10; patients who received tocilizumab had higher incidence of IL-6 and sIL2R elevations. Pre-tocilizumab IL-6 levels increased with disease severity (p = .0151). Both IL-6 and sIL2R levels significantly increased after administration of tocilizumab in all severity groups; IL-10 levels decreased in severe (p = .0203), but not moderate or critical, patients after they received tocilizumab. Cluster analysis revealed association between higher admission IL-6, sIL2R, and CRP levels and disease severity. Mean IL-6, sIL2R, and D-dimer were associated with mortality, and tocilizumab-treated patients with elevated IL-6, IL-10, and D-dimer were more likely to also receive glucocorticoids. Accessible clinical cytokine panels may be useful for monitoring response to treatment in COVID-19. The increase in sIL2R post-tocilizumab, despite administration of glucocorticoids, may indicate the need for combination therapy in order to modulate more than one hyperinflammatory pathway in COVID-19. We also discuss the role of cytokines as potential biomarkers for use of adjunct glucocorticoid therapy.

Authors+Show Affiliations

Section of Rheumatology, Allergy & Immunology, Yale University School of Medicine, TAC S469c, 333 Cedar Street, New Haven, CT, 06511, USA. veronica.azmy@yale.edu.Section of Rheumatology, Allergy & Immunology, Yale University School of Medicine, TAC S469c, 333 Cedar Street, New Haven, CT, 06511, USA.Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA. Department of Pharmacy Services, Yale New Haven Hospital, New Haven, CT, USA.Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA.Section of Rheumatology, Allergy & Immunology, Yale University School of Medicine, TAC S469c, 333 Cedar Street, New Haven, CT, 06511, USA. Department of Allergy and Immunology, VA Medical Center, West Haven, CT, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33459964

Citation

Azmy, Veronica, et al. "Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients With COVID-19." Journal of Clinical Immunology, vol. 41, no. 4, 2021, pp. 738-747.
Azmy V, Kaman K, Tang D, et al. Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19. J Clin Immunol. 2021;41(4):738-747.
Azmy, V., Kaman, K., Tang, D., Zhao, H., Dela Cruz, C., Topal, J. E., Malinis, M., & Price, C. C. (2021). Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19. Journal of Clinical Immunology, 41(4), 738-747. https://doi.org/10.1007/s10875-020-00949-6
Azmy V, et al. Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients With COVID-19. J Clin Immunol. 2021;41(4):738-747. PubMed PMID: 33459964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19. AU - Azmy,Veronica, AU - Kaman,Kelsey, AU - Tang,Daiwei, AU - Zhao,Hongyu, AU - Dela Cruz,Charles, AU - Topal,Jeffrey E, AU - Malinis,Maricar, AU - Price,Christina C, Y1 - 2021/01/18/ PY - 2020/10/03/received PY - 2020/12/16/accepted PY - 2021/1/19/pubmed PY - 2021/5/5/medline PY - 2021/1/18/entrez KW - COVID-19 KW - SARS-CoV-2 KW - cytokine panel KW - cytokine profile KW - cytokine release syndrome KW - glucocorticoids KW - interleukin-10 KW - interleukin-2 receptor (soluble) KW - tocilizumab SP - 738 EP - 747 JF - Journal of clinical immunology JO - J Clin Immunol VL - 41 IS - 4 N2 - We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical SARS-CoV-2 infection. Disease severity was based on maximum oxygen requirement during hospital stay to maintain SpO2 > 93% (moderate, 0-3 L NC; severe, 4-6 L NC or non-rebreather; critical, HFNC, NIPPV, or MV). All patients were treated using the institution's treatment algorithm, which included consideration of tocilizumab for severe and critical disease. The most common cytokine elevations among all patients included IL-6, sIL2R, IFN-γ, and IL-10; patients who received tocilizumab had higher incidence of IL-6 and sIL2R elevations. Pre-tocilizumab IL-6 levels increased with disease severity (p = .0151). Both IL-6 and sIL2R levels significantly increased after administration of tocilizumab in all severity groups; IL-10 levels decreased in severe (p = .0203), but not moderate or critical, patients after they received tocilizumab. Cluster analysis revealed association between higher admission IL-6, sIL2R, and CRP levels and disease severity. Mean IL-6, sIL2R, and D-dimer were associated with mortality, and tocilizumab-treated patients with elevated IL-6, IL-10, and D-dimer were more likely to also receive glucocorticoids. Accessible clinical cytokine panels may be useful for monitoring response to treatment in COVID-19. The increase in sIL2R post-tocilizumab, despite administration of glucocorticoids, may indicate the need for combination therapy in order to modulate more than one hyperinflammatory pathway in COVID-19. We also discuss the role of cytokines as potential biomarkers for use of adjunct glucocorticoid therapy. SN - 1573-2592 UR - https://www.unboundmedicine.com/medline/citation/33459964/Cytokine_Profiles_Before_and_After_Immune_Modulation_in_Hospitalized_Patients_with_COVID_19_ L2 - https://doi.org/10.1007/s10875-020-00949-6 DB - PRIME DP - Unbound Medicine ER -