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Sökning: onr:"swepub:oai:DiVA.org:uu-425489" > Complement C3 vs C5...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006601naa a2200649 4500
001oai:DiVA.org:uu-425489
003SwePub
008201118s2020 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4254892 URI
0247 a https://doi.org/10.1016/j.clim.2020.1085982 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Mastellos, Dimitrios C.u Natl Ctr Sci Res Demokritos, Athens, Greece.4 aut
2451 0a Complement C3 vs C5 inhibition in severe COVID-19 :b Early clinical findings reveal differential biological efficacy
264 1b ACADEMIC PRESS INC ELSEVIER SCIENCE,c 2020
338 a print2 rdacarrier
520 a Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. Deregulated complement activation may fuel cytokine-driven hyper-inflammation, thrombotic microangiopathy and NET-driven immunothrombosis, thereby leading to multi-organ failure. Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2 infection. Whether blockade of terminal complement effectors (C5, C5a, or C5aR1) may elicit similar outcomes to upstream intervention at the level of C3 remains debated. Here we compare the efficacy of the C5-targeting monoclonal antibody eculizumab with that of the compstatin-based C3-targeted drug candidate AMY-101 in small independent cohorts of severe COVID-19 patients. Our exploratory study indicates that therapeutic complement inhibition abrogates COVID-19 hyper-inflammation. Both C3 and C5 inhibitors elicit a robust anti-inflammatory response, reflected by a steep decline in C-reactive protein and IL-6 levels, marked lung function improvement, and resolution of SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). C3 inhibition afforded broader therapeutic control in COVID-19 patients by attenuating both C3a and sC5b-9 generation and preventing FB consumption. This broader inhibitory profile was associated with a more robust decline of neutrophil counts, attenuated neutrophil extracellular trap (NET) release, faster serum LDH decline, and more prominent lymphocyte recovery. These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the Medical Area0 (SwePub)301102 hsv//eng
653 a COVID-19
653 a Thromboinflammation
653 a C3 inhibition
653 a C5 blockade
653 a AMY-101
653 a Eculizumab
653 a Drug efficacy
653 a Biomarkers
7001 a Pires da Silva, Bruno G. P.u Univ Sao Paulo, Sch Med, Dept Med Imaging Hematol & Clin Oncol, Ribeirao Preto, Brazil.4 aut
7001 a Fonseca, Benedito A. L.u Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, Ribeirao Preto, Brazil.4 aut
7001 a Fonseca, Natasha P.u Univ Sao Paulo, Sch Med, Dept Med Imaging Hematol & Clin Oncol, Ribeirao Preto, Brazil.4 aut
7001 a Auxiliadora-Martins, Mariau Univ Sao Paulo, Ribeirao Preto Sch Med, Intens Care Unit, Univ Hosp, Ribeirao Preto, Brazil.4 aut
7001 a Mastaglio, Sarau IRCCS San Raffaele Sci Inst, Hematol & Bone Marrow Transplantat Unit, Milan, Italy.4 aut
7001 a Ruggeri, Annalisau IRCCS San Raffaele Sci Inst, Hematol & Bone Marrow Transplantat Unit, Milan, Italy.4 aut
7001 a Sironi, Marinau IRCCS, Humanitas Clin & Res Ctr, Milan, Italy.4 aut
7001 a Radermacher, Peteru Univ Hosp Ulm, Sekt Anasthesiol Pathophysiol & Verfahrensentwick, Ulm, Germany.4 aut
7001 a Chrysanthopoulou, Akriviu Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.4 aut
7001 a Skendros, Panagiotisu Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.4 aut
7001 a Ritis, Konstantinosu Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.4 aut
7001 a Manfra, Ileniau AORN San Giuseppe Moscati, Hematol & Hematopoiet Stem Cell Transplantat Unit, Avellino, Italy.4 aut
7001 a Iacobelli, Simonau Univ Roma Tor Vergata, Dept Biol, Rome, Italy.4 aut
7001 a Huber-Lang, Markusu Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.4 aut
7001 a Nilsson, Bou Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)bonils
7001 a Yancopoulou, Despinau Amyndas Pharmaceut, Glifadha, Greece.4 aut
7001 a Connolly, E. Sanderu Columbia Univ, Dept Neurol Surg, New York, NY USA.4 aut
7001 a Garlanda, Ceciliau IRCCS, Humanitas Clin & Res Ctr, Milan, Italy.;Humanitas Univ, Milan, Italy.4 aut
7001 a Ciceri, Fabiou IRCCS San Raffaele Sci Inst, Hematol & Bone Marrow Transplantat Unit, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.4 aut
7001 a Risitano, Antonio M.u AORN San Giuseppe Moscati, Hematol & Hematopoiet Stem Cell Transplantat Unit, Avellino, Italy.;Federico II Univ Naples, Naples, Italy.4 aut
7001 a Calado, Rodrigo T.u Univ Sao Paulo, Sch Med, Dept Med Imaging Hematol & Clin Oncol, Ribeirao Preto, Brazil.4 aut
7001 a Lambris, John D.u Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.4 aut
7102 a Natl Ctr Sci Res Demokritos, Athens, Greece.b Univ Sao Paulo, Sch Med, Dept Med Imaging Hematol & Clin Oncol, Ribeirao Preto, Brazil.4 org
7730 t Clinical Immunologyd : ACADEMIC PRESS INC ELSEVIER SCIENCEg 220q 220x 1521-6616x 1521-7035
8564 u https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501834
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-425489
8564 8u https://doi.org/10.1016/j.clim.2020.108598

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