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Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study

Valentina Giudice, Pasquale Pagliano, Alessandro Vatrella, Alfonso Masullo, S Poto, Benedetto Polverino, Renato Gammaldi, Angelantonio Maglio, Carmine Sellitto, Carolina Vitale, Bianca Serio, Bianca Cuffa, Anna Borrelli, Carmine Vecchione, Amelia Filippelli, Carmine Selleri

2020Frontiers in Pharmacology119 citationsDOIOpen Access PDF

Abstract

To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.

Topics & Concepts

RuxolitinibEculizumabMedicineAcute respiratory distressSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)Middle East respiratory syndrome coronavirus2019-20 coronavirus outbreakRespiratory distressImmunologyRespiratory systemIntensive care medicineVirologyInternal medicineAntibodyLungComplement systemDiseaseAnesthesiaMyelofibrosisInfectious disease (medical specialty)Bone marrowOutbreakCOVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchLong-Term Effects of COVID-19