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Complement C3 inhibition in severe COVID-19 using compstatin AMY-101

Skendros, Panagiotis (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Germanidis, Georgios (author)
Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Internal Med 1, Thessaloniki, Greece.;Aristotle Univ Thessaloniki, Sch Med, Special Unit Biomed Res & Educ SUBRE, Basic & Translat Res Unit, Thessaloniki, Greece.
Mastellos, Dimitrios C. (author)
Natl Ctr Sci Res Demokritos, Athens, Greece.
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Antoniadou, Christina (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Gavriilidis, Efstratios (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Kalopitas, Georgios (author)
Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Internal Med 1, Thessaloniki, Greece.;Aristotle Univ Thessaloniki, Sch Med, Special Unit Biomed Res & Educ SUBRE, Basic & Translat Res Unit, Thessaloniki, Greece.
Samakidou, Anna (author)
Gen Univ Hosp Larissa, Natl & European Expertise Ctr Greece Autoimmune L, Dept Med, Larisa, Greece.;Gen Univ Hosp Larissa, Natl & European Expertise Ctr Greece Autoimmune L, Res Lab Internal Med, Larisa, Greece.
Liontos, Angelos (author)
Univ Ioannina, Fac Med, Sch Hlth Sci, Dept Internal Med, Ioannina, Greece.
Chrysanthopoulou, Akrivi (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Ntinopoulou, Maria (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Kogias, Dionysios (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Karanika, Ioanna (author)
Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Internal Med 1, Thessaloniki, Greece.;Aristotle Univ Thessaloniki, Sch Med, Special Unit Biomed Res & Educ SUBRE, Basic & Translat Res Unit, Thessaloniki, Greece.
Smyrlis, Andreas (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Cepaityte, Dainora (author)
Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Internal Med 1, Thessaloniki, Greece.;Aristotle Univ Thessaloniki, Sch Med, Special Unit Biomed Res & Educ SUBRE, Basic & Translat Res Unit, Thessaloniki, Greece.
Fotiadou, Iliana (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Zioga, Nikoleta (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Mitroulis, Ioannis (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Gatselis, Nikolaos K. (author)
Gen Univ Hosp Larissa, Natl & European Expertise Ctr Greece Autoimmune L, Dept Med, Larisa, Greece.;Gen Univ Hosp Larissa, Natl & European Expertise Ctr Greece Autoimmune L, Res Lab Internal Med, Larisa, Greece.
Papagoras, Charalampos (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Metallidis, Simeon (author)
Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Internal Med 1, Thessaloniki, Greece.;Aristotle Univ Thessaloniki, Sch Med, Special Unit Biomed Res & Educ SUBRE, Basic & Translat Res Unit, Thessaloniki, Greece.
Milionis, Haralampos (author)
Univ Ioannina, Fac Med, Sch Hlth Sci, Dept Internal Med, Ioannina, Greece.
Dalekos, George N. (author)
Gen Univ Hosp Larissa, Natl & European Expertise Ctr Greece Autoimmune L, Dept Med, Larisa, Greece.;Gen Univ Hosp Larissa, Natl & European Expertise Ctr Greece Autoimmune L, Res Lab Internal Med, Larisa, Greece.
Willems, Loek (author)
Hycult Biotechnol, R&D Dept, Uden, Netherlands.
Persson, Barbro (author)
Uppsala universitet,Vaskulärbiologi
Manivel, Vivek Anand (author)
Uppsala universitet,Vaskulärbiologi
Nilsson, Bo (author)
Uppsala universitet,Vaskulärbiologi
Connolly, E. Sander (author)
Columbia Univ, Dept Neurol Surg, New York, NY USA.
Iacobelli, Simona (author)
Univ Roma Tor Vergata, Dept Biol, Rome, Italy.
Papadopoulos, Vasileios (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Calado, Rodrigo T. (author)
Univ Sao Paulo, Sch Med, Dept Med Imaging Hematol & Oncol, Ribeirao Preto, Brazil.
Huber-Lang, Markus (author)
Ulm Univ Hosp, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
Risitano, Antonio M. (author)
AORN Moscati Avellino, Avellino, Italy.;Federico II Univ Naples, Naples, Italy.
Yancopoulou, Despina (author)
Amyndas Pharmaceut, Glifadha, Greece.
Ritis, Konstantinos (author)
Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece.;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece.
Lambris, John D. (author)
Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
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Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Internal Med 1, Alexandroupolis, Greece;Democritus Univ Thrace, Univ Hosp Alexandroupolis, Lab Mol Hematol, Alexandroupolis, Greece. Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Internal Med 1, Thessaloniki, Greece.;Aristotle Univ Thessaloniki, Sch Med, Special Unit Biomed Res & Educ SUBRE, Basic & Translat Res Unit, Thessaloniki, Greece. (creator_code:org_t)
American Association for the Advancement of Science (AAAS), 2022
2022
English.
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:33
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 <= 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

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