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Comparative Survival Analysis of Immunomodulatory Therapy for Coronavirus Disease 2019 Cytokine Storm
Sonali Narain1, Dimitre G Stefanov2, Alice S Chau3
1Division of Rheumatology, Department of Medicine, Northwell Health, Great Neck, NY; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Hempstead, NY.
Insights
Immunomodulatory therapies, including corticosteroids and tocilizumab, significantly reduced mortality in patients with COVID-19 cytokine storm. This combination therapy demonstrated superior survival outcomes compared to standard care.
Area of Science:
- Critical care medicine
- Infectious diseases
- Pharmacology
Background:
- Cytokine storm is a critical indicator of severe COVID-19 and increased mortality.
- Repurposed immunomodulatory treatments aim to improve survival rates in COVID-19 patients.
Purpose of the Study:
- To investigate the efficacy of immunomodulatory therapies in improving survival for patients experiencing a COVID-19 cytokine storm (CCS).
Main Methods:
- Retrospective analysis of electronic health records for hospitalized COVID-19 patients (March-April 2020).
- CCS defined by elevated ferritin, CRP, or LDH levels.
- Patients categorized into standard of care (SoC) or treated with corticosteroids, tocilizumab, anakinra, or combinations.
Main Results:
- Corticosteroids combined with tocilizumab showed significantly lower mortality versus SoC (HR, 0.44; P < .0001).
- Corticosteroids alone or with anakinra also improved survival compared to SoC (HR, 0.66 and 0.68, respectively; P < .0001).
- The corticosteroid and tocilizumab combination yielded superior survival compared to other treatment groups.
Conclusions:
- Corticosteroids, particularly in combination with tocilizumab, significantly reduce hospital mortality in patients with COVID-19 cytokine storm.
- Immunomodulatory treatments offer a viable strategy for improving survival outcomes in severe COVID-19 cases.
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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