Lessons from pathophysiology : Use of individualized combination treatments with immune interventional agents to tackle severe respiratory failure in patients with COVID-19
Copyright © 2021. Published by Elsevier B.V..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
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| Enthalten in: |
European journal of internal medicine - 88(2021) vom: 15. Juni, Seite 52-62 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dalekos, George N [VerfasserIn] |
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| Links: |
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| Themen: |
Anakinra |
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| Anmerkungen: |
Date Completed 02.06.2021 Date Revised 02.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejim.2021.03.026 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM323760651 |
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| 100 | 1 | |a Dalekos, George N |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lessons from pathophysiology |b Use of individualized combination treatments with immune interventional agents to tackle severe respiratory failure in patients with COVID-19 |
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| 500 | |a Date Revised 02.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021. Published by Elsevier B.V. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anakinra | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a IL-1 | |
| 650 | 4 | |a IL-6 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Tocilizumab | |
| 650 | 7 | |a Interleukin 1 Receptor Antagonist Protein |2 NLM | |
| 700 | 1 | |a Stefos, Aggelos |e verfasserin |4 aut | |
| 700 | 1 | |a Georgiadou, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Lygoura, Vasiliki |e verfasserin |4 aut | |
| 700 | 1 | |a Michail, Anastasia |e verfasserin |4 aut | |
| 700 | 1 | |a Ntaios, George |e verfasserin |4 aut | |
| 700 | 1 | |a Samakidou, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Giannoulis, George |e verfasserin |4 aut | |
| 700 | 1 | |a Gabeta, Stella |e verfasserin |4 aut | |
| 700 | 1 | |a Vlychou, Marianna |e verfasserin |4 aut | |
| 700 | 1 | |a Petinaki, Efthymia |e verfasserin |4 aut | |
| 700 | 1 | |a Leventogiannis, Konstantinos |e verfasserin |4 aut | |
| 700 | 1 | |a Giamarellos-Bourboulis, Evangelos J |e verfasserin |4 aut | |
| 700 | 1 | |a Gatselis, Nikolaos K |e verfasserin |4 aut | |
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