TY - JOUR
T1 - Comparative Survival Analysis of Immunomodulatory Therapy for Coronavirus Disease 2019 Cytokine Storm
AU - Northwell COVID-19 Research Consortium
AU - Narain, Sonali
AU - Stefanov, Dimitre G.
AU - Chau, Alice S.
AU - Weber, Andrew G.
AU - Marder, Galina
AU - Kaplan, Blanka
AU - Malhotra, Prashant
AU - Bloom, Ona
AU - Liu, Audrey
AU - Lesser, Martin L.
AU - Hajizadeh, Negin
AU - Cohen, Stuart L.
AU - Cookingham, Jennifer
AU - Hirschwerk, David A.
AU - Maria, Naomi I.
AU - Satapathy, Sanjaya K.
AU - Sison, Cristina
AU - Taylor, Matthew
AU - Qiu, Michael
N1 - Funding Information:
FUNDING/SUPPORT: A. S. C. was supported by The Primary Immune Deficiency Treatment Consortium [Grant U54 AI 082973], funded jointly by the National Center for Advancing Translational Sciences and the National Institute of Allergy and Infectious Diseases . O. B. was supported by the United States Department of Defense [Grant W81XWH-15-1-0614] and the New York State Spinal Cord Injury Research Board [Grant DOH01-ISSCI6-2016-00018]. N. H. was supported by a grant from the Patient Centered Outcomes Research Institute [Grant AD-1511-33066].
Publisher Copyright:
© 2020 American College of Chest Physicians
PY - 2021/3
Y1 - 2021/3
N2 - Background: Cytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. Research Question: Do immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)? Study Design and Methods: We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, > 700 ng/mL; C-reactive protein (CRP), > 30 mg/dL; or lactate dehydrogenase (LDH), > 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-IL-6 antibody (tocilizumab), or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. Results: Five thousand seven hundred seventy-six patients met the inclusion criteria. The most common comorbidities were hypertension (44%-59%), diabetes (32%-46%), and cardiovascular disease (5%-14%). Patients most frequently met criteria with high LDH (76.2%) alone or in combination, followed by ferritin (63.2%) and CRP (8.4%). More than 80% of patients showed an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination showed lower mortality compared with patients receiving standard-of-care (SoC) treatment (hazard ratio [HR], 0.44; 95% CI, 0.35-0.55; P < .0001) and with patients treated with corticosteroids alone (HR, 0.66; 95% CI, 0.53-0.83; P = .004) or in combination with anakinra (HR, 0.64; 95% CI, 0.50-0.81; P = .003). Corticosteroids when administered alone (HR, 0.66; 95% CI, 0.57-0.76; P < .0001) or in combination with tocilizumab (HR, 0.43; 95% CI, 0.35-0.55; P < .0001) or anakinra (HR, 0.68; 95% CI, 0.57-0.81; P < .0001) improved hospital survival compared with SoC treatment. Interpretation: The combination of corticosteroids with tocilizumab showed superior survival outcome when compared with SoC treatment as well as treatment with corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with CCS compared with patients receiving SoC treatment.
AB - Background: Cytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. Research Question: Do immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)? Study Design and Methods: We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, > 700 ng/mL; C-reactive protein (CRP), > 30 mg/dL; or lactate dehydrogenase (LDH), > 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-IL-6 antibody (tocilizumab), or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. Results: Five thousand seven hundred seventy-six patients met the inclusion criteria. The most common comorbidities were hypertension (44%-59%), diabetes (32%-46%), and cardiovascular disease (5%-14%). Patients most frequently met criteria with high LDH (76.2%) alone or in combination, followed by ferritin (63.2%) and CRP (8.4%). More than 80% of patients showed an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination showed lower mortality compared with patients receiving standard-of-care (SoC) treatment (hazard ratio [HR], 0.44; 95% CI, 0.35-0.55; P < .0001) and with patients treated with corticosteroids alone (HR, 0.66; 95% CI, 0.53-0.83; P = .004) or in combination with anakinra (HR, 0.64; 95% CI, 0.50-0.81; P = .003). Corticosteroids when administered alone (HR, 0.66; 95% CI, 0.57-0.76; P < .0001) or in combination with tocilizumab (HR, 0.43; 95% CI, 0.35-0.55; P < .0001) or anakinra (HR, 0.68; 95% CI, 0.57-0.81; P < .0001) improved hospital survival compared with SoC treatment. Interpretation: The combination of corticosteroids with tocilizumab showed superior survival outcome when compared with SoC treatment as well as treatment with corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with CCS compared with patients receiving SoC treatment.
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U2 - 10.1016/j.chest.2020.09.275
DO - 10.1016/j.chest.2020.09.275
M3 - Article
C2 - 33075378
AN - SCOPUS:85100398427
SN - 0012-3692
VL - 159
SP - 933
EP - 948
JO - CHEST
JF - CHEST
IS - 3
ER -