Τίτλος:
Lessons from pathophysiology: Use of individualized combination treatments with immune interventional agents to tackle severe respiratory failure in patients with COVID-19
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2021
Συγγραφείς:
Dalekos, G.N.
Stefos, A.
Georgiadou, S.
Lygoura, V.
Michail, A.
Ntaios, G.
Samakidou, A.
Giannoulis, G.
Gabeta, S.
Vlychou, M.
Petinaki, E.
Leventogiannis, K.
Giamarellos-Bourboulis, E.J.
Gatselis, N.K.
Περιοδικό:
European Journal of Internal Medicine
Λέξεις-κλειδιά:
alanine aminotransferase; anakinra; antibiotic agent; C reactive protein; D dimer; dexamethasone; enoxaparin; ferritin; granulocyte colony stimulating factor; hydrocortisone; immunoglobulin; lactate dehydrogenase; methylprednisolone; remdesivir; tocilizumab; interleukin 1 receptor blocking agent, adult; adult respiratory distress syndrome; alanine aminotransferase level; algorithm; anasarca; Article; bacteremia; bacterial pneumonia; bloodstream infection; breathing rate; Candida; catheter infection; chronic obstructive lung disease; combination drug therapy; comorbidity; computer assisted tomography; controlled study; coronary artery disease; coronavirus disease 2019; COVID-19 testing; diabetes mellitus; disease duration; disease severity; drug half life; drug megadose; drug pulse therapy; drug withdrawal; female; ferritin blood level; follow up; fraction of inspired oxygen; heart failure; hematoma; hospital admission; hospital infection; hospital patient; hospitalization; human; hypertension; immunotherapy; injection site reaction; intubation; Kolmogorov Smirnov test; lactate dehydrogenase blood level; leukocyte count; lower respiratory tract infection; lung embolism; lung infiltrate; lymphocyte count; lymphocytopenia; major clinical study; male; mesenteric vein thrombosis; mortality rate; nasopharyngeal swab; neutropenia; neutrophil count; obesity; observational study; osteoporosis; oxygen saturation; oxygen tension; oxygen therapy; pathophysiology; peripheral edema; phase 3 clinical trial (topic); platelet count; pneumonia; prospective study; pulse oximetry; respiratory failure; risk factor; secondary infection; single drug dose; Stenotrophomonas maltophilia; thorax radiography; thrombocytopenia; treatment contraindication; treatment duration; treatment outcome; aged; middle aged; respiratory distress syndrome; respiratory failure, Aged; COVID-19; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Respiratory Distress Syndrome; Respiratory Insufficiency; SARS-CoV-2; Treatment Outcome
DOI:
10.1016/j.ejim.2021.03.026
