Gaurang Vaidya1, Lawrence S C Czer2, Jon Kobashigawa1, Michelle Kittleson1, Jignesh Patel1, David Chang1, Evan Kransdorf1, Anuja Shikhare3, Hai Tran4, Ashley Vo5, Noriko Ammerman5, Edmund Huang5, Rachel Zabner6, Stanley Jordan5. 1. Cedars-Sinai Smidt Heart Institute, Heart Transplant Program, Cedars Sinai Medical Center, Los Angeles, California. 2. Cedars-Sinai Smidt Heart Institute, Heart Transplant Program, Cedars Sinai Medical Center, Los Angeles, California. Electronic address: Lawrence.Czer@cshs.org. 3. Department of Medicine, William Beaumont Hospital, Royal Oak, Michigan. 4. Department of Pharmacy Services, Cedars Sinai Medical Center, Los Angeles, California. 5. Comprehensive Transplant Center, Transplant Immunotherapy Program, Cedars Sinai Medical Center, Los Angeles, California. 6. Division of Infectious Diseases, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California.
Abstract
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by an overwhelming cytokine response. Various treatment strategies have been attempted. METHODS AND RESULTS: A 61-year-old man with heart transplantation in 2017 presented with fever, cough, and dyspnea, and was confirmed positive for coronavirus disease 2019 (COVID-19). Laboratory tests showed significant elevations in C-reactive protein and interleukin-6 (IL-6). Echocardiogram showed left ventricular ejection fraction 58% (with ejection fraction 57% 6 months prior). Given the lack of clear management guidelines, the patient was initially managed symptomatically. However, the patient subsequently had a rapid respiratory deterioration with worsening inflammatory markers on day 5 of admission. Tocilizumab (anti-IL-6R) was in low supply in the hospital. The patient was offered clazakizumab (anti-IL-6) for compassionate use. Patient received 25 mg intravenously × 1 dose. Within 24 hours, he showed significant improvement in symptoms, oxygen requirements, radiological findings, and inflammatory markers. There was a transient leukopenia that improved in 4 days. He was discharged home on day 11, with negative nasopharyngeal SARS-CoV-2 PCR as an outpatient on day 35, development of positive serum COVID-19 IgG antibody, and he continued to do well on day 60, with no heart-related symptoms. CONCLUSION: Clazakizumab is a monoclonal antibody against human IL-6, which may be helpful in inhibiting the cytokine response to SARS-CoV-2 in COVID-19. Although not yet FDA approved, it is being investigated for treatment of renal antibody-mediated rejection. Clinical trials of clazakizumab for treatment of COVID-19 are underway worldwide.
BACKGROUND:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by an overwhelming cytokine response. Various treatment strategies have been attempted. METHODS AND RESULTS: A 61-year-old man with heart transplantation in 2017 presented with fever, cough, and dyspnea, and was confirmed positive for coronavirus disease 2019 (COVID-19). Laboratory tests showed significant elevations in C-reactive protein and interleukin-6 (IL-6). Echocardiogram showed left ventricular ejection fraction 58% (with ejection fraction 57% 6 months prior). Given the lack of clear management guidelines, the patient was initially managed symptomatically. However, the patient subsequently had a rapid respiratory deterioration with worsening inflammatory markers on day 5 of admission. Tocilizumab (anti-IL-6R) was in low supply in the hospital. The patient was offered clazakizumab (anti-IL-6) for compassionate use. Patient received 25 mg intravenously × 1 dose. Within 24 hours, he showed significant improvement in symptoms, oxygen requirements, radiological findings, and inflammatory markers. There was a transient leukopenia that improved in 4 days. He was discharged home on day 11, with negative nasopharyngeal SARS-CoV-2 PCR as an outpatient on day 35, development of positive serum COVID-19 IgG antibody, and he continued to do well on day 60, with no heart-related symptoms. CONCLUSION:Clazakizumab is a monoclonal antibody against humanIL-6, which may be helpful in inhibiting the cytokine response to SARS-CoV-2 in COVID-19. Although not yet FDA approved, it is being investigated for treatment of renal antibody-mediated rejection. Clinical trials of clazakizumab for treatment of COVID-19 are underway worldwide.
Authors: Maria Trovato; Salvatore Sciacchitano; Alessio Facciolà; Andrea Valenti; Giuseppa Visalli; Angela Di Pietro Journal: Int J Mol Med Date: 2021-04-28 Impact factor: 4.101
Authors: Jan Brábek; Milan Jakubek; Fréderic Vellieux; Jiří Novotný; Michal Kolář; Lukáš Lacina; Pavol Szabo; Karolína Strnadová; Daniel Rösel; Barbora Dvořánková; Karel Smetana Journal: Int J Mol Sci Date: 2020-10-26 Impact factor: 5.923