Abstract
Aims 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.
【저자키워드】 COVID-19, SARS-CoV-2, Anakinra, Tocilizumab, IL-6, IL-1, 【초록키워드】 Corticosteroid, Treatment, Respiratory failure, Mortality, severe respiratory failure, intubation, ferritin, Intervention, survival, Secondary infection, management, Algorithm, adverse event, Patient, Older age, combination treatment, mortality rate, patients, single dose, acute respiratory distress, Coronavirus-2, Combination, Hypothesis, administration, Immunomodulatory agent, death rate, acute respiratory syndrome, Endpoint, moderate disease, median age, independent risk factors, syndrome, comparator, inflammatory process, Standard-of-care, Administered, Arm, IMPROVE, Result, applied, treated, significantly higher, Significant, baseline, with COVID-19, 【제목키워드】 severe respiratory failure, immune, combination treatment, lesson, patients with COVID-19,