• George N Dalekos, Aggelos Stefos, Sarah Georgiadou, Vasiliki Lygoura, Anastasia Michail, George Ntaios, Anna Samakidou, George Giannoulis, Stella Gabeta, Marianna Vlychou, Efthymia Petinaki, Konstantinos Leventogiannis, Evangelos J Giamarellos-Bourboulis, and Nikolaos K Gatselis.
• Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110 Larissa, Greece. Electronic address: dalekos@med.uth.gr.
• Eur. J. Intern. Med. 2021 Jun 1; 88: 52-62.

AbstractAims Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may lead to the development of severe respiratory failure. In hospitalized-patients, prompt interruption of the virus-driven inflammatory process by using combination treatments seems theoretically of outmost importance. Our aim was to investigate the hypothesis of multifaceted management of these patients. Methods A treatment algorithm based on ferritin was applied in 311 patients (67.2% males; median age 63-years; moderate disease, n=101; severe, n=210). Patients with ferritin <500ng/ml received anakinra 2-4mg/kg/day ± corticosteroids (Arm A, n=142) while those with ≥500ng/ml received anakinra 5-8mg/kg/day with corticosteroids and γ-globulins (Arm B, n=169). In case of no improvement a single dose of tocilizumab (8mg/kg; maximum 800mg) was administered with the potential of additional second and/or third pulses. Treatment endpoints were the rate of the development of respiratory failure necessitating intubation and the SARS-CoV-2-related mortality. The proposed algorithm was also validated in matched hospitalized-patients treated with standard-of-care during the same period. Results In overall, intubation and mortality rates were 5.8% and 5.1% (0% in moderate; 8.6% and 7.6% in severe). Low baseline pO2/FiO2 and older age were independent risk factors. Comparators had significantly higher intubation (HR=7.4; 95%CI: 4.1-13.4; p<0.001) and death rates (HR=4.5, 95%CI: 2.1-9.4, p<0.001). Significant adverse events were rare, including severe secondary infections in only 7/311 (2.3%). Conclusions Early administration of personalized combinations of immunomodulatory agents may be life-saving in hospitalized-patients with COVID-19. An immediate intervention (the sooner the better) could be helpful to avoid development of full-blown acute respiratory distress syndrome and improve survival.Copyright © 2021. Published by Elsevier B.V.

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