Περίληψη:
Background It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19. Methods 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied. Results 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95%CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata. Conclusions Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance. Trial Registration: ClinicalTrials.gov, NCT04357366. © 2021, eLife Sciences Publications Ltd. All rights reserved.
Συγγραφείς:
Kyriazopoulou, E.
Panagopoulos, P.
Metallidis, S.
Dalekos, G.N.
Poulakou, G.
Gatselis, N.
Karakike, E.
Saridaki, M.
Loli, G.
Stefos, A.
Prasianaki, D.
Georgiadou, S.
Tsachouridou, O.
Petrakis, V.
Tsiakos, K.
Kosmidou, M.
Lygoura, V.
Dareioti, M.
Milionis, H.
Papanikolaou, I.C.
Akinosoglou, K.
Myrodia, D.-M.
Gravvani, A.
Stamou, A.
Gkavogianni, T.
Katrini, K.
Marantos, T.
Trontzas, I.P.
Syrigos, K.
Chatzis, L.
Chatzis, S.
Vechlidis, N.
Avgoustou, C.
Chalvatzis, S.
Kyprianou, M.
van der Meer, J.W.M.
Eugen-Olsen, J.
Netea, M.G.
Giamarellos-Bourboulis, E.J.
Λέξεις-κλειδιά:
anakinra; azithromycin; beta lactamase inhibitor; biological marker; C reactive protein; carbapenem; CD163 antigen; ceftaroline; cephalosporin; dexamethasone; ferritin; glycopeptide; hydroxychloroquine; interleukin 10; interleukin 1beta; interleukin 2; interleukin 6; levofloxacin; moxifloxacin; piperacillin plus tazobactam; procalcitonin; remdesivir; soluble urokinase plasminogen activator receptor; unclassified drug; antiinflammatory agent; CD163 antigen; cell surface receptor; differentiation antigen; interleukin 1 receptor blocking agent; interleukin 10; interleukin 6; leukocyte antigen; urokinase receptor, acute kidney failure; adult; allergic reaction; anemia; APACHE; arterial oxygen tension; Article; bacterial infection; Candida albicans; Charlson Comorbidity Index; comorbidity; controlled study; coronavirus disease 2019; cytokine production; electrolyte disturbance; enzyme immunoassay; Escherichia coli; female; flow cytometry; gastrointestinal symptom; headache; health care quality; heart arrhythmia; hospitalization; hospitalization cost; human; leukocyte count; leukopenia; liver function test; lower respiratory tract infection; lung edema; lymphocyte count; major clinical study; male; mortality; noninvasive ventilation; outcome assessment; peripheral blood mononuclear cell; platelet count; pneumonia; Pneumonia Severity Index; real time polymerase chain reaction; respiratory failure; Sequential Organ Failure Assessment Score; shock; Streptococcus pneumoniae; thrombocytopenia; thromboembolism; aged; artificial ventilation; blood; clinical trial; drug therapy; incidence; metabolism; middle aged; respiratory failure; subcutaneous drug administration; treatment outcome; very elderly, Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antigens, CD; Antigens, Differentiation, Myelomonocytic; COVID-19; Female; Humans; Incidence; Injections, Subcutaneous; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-6; Male; Middle Aged; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Respiration, Artificial; Respiratory Insufficiency; SARS-CoV-2; Standard of Care; Treatment Outcome
