Background Cytokine storm is a marker of COVID-19 illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. Research Question To identify if immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm. 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. Cytokine storm was defined by inflammatory markers: ferritin >700ng/mL, C-reactive protein >30mg/dL or lactate dehydrogenase >300U/L. Patients were subdivided into six groups—no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-interleukin 6 antibody (tocilizumab) or anti-interleukin-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. Results 5,776 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 lactate dehydrogenase (76.2%) alone or in combination, followed by ferritin (63.2%) and C-reactive protein (8.4%). More than 80% of patients had an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination had lower mortality compared to standard of care (Hazard Ratio (HR):0.44, 95% confidence interval (CI): 0.35-0.55; p <0.0001) and when compared to corticosteroids alone (HR:0.66, 95%CI: 0.53-0.83; p-value=0.004), or in combination with anakinra (HR:0.64, 95%CI:0.50-0.81; p-value=0.003) . Corticosteroids when administered alone (HR:0.66, 95%CI:0.57-0.76; p<0.0001) or in combination with tocilizumab (HR:0.43, 95%CI:0.35-0.55; p<0.0001) or anakinra (HR:0.68, 95%CI:0.57-0.81; p<0.0001) improved hospital survival compared to standard of care. Interpretation The combination of corticosteroids with tocilizumab had superior survival outcome when compared to standard of care and 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 COVID-19 cytokine storm compared to standard of care.
Background Mechanically ventilated patients with COVID-19 have a mortality of 24–53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. Methods Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19—including three requiring veno-venous extracorporeal membrane oxygenation—treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. Results The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. Conclusions Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.
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