Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients
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- Malgorzata Mikulska
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Chiara Sepulcri
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Chiara Dentone
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Federica Magne
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Elisa Balletto
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Federico Baldi
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Laura Labate
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Chiara Russo
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Michele Mirabella
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Laura Magnasco
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Carmen Di Grazia
- Ematologia e Terapie Cellulari, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Chiara Ghiggi
- Ematologia e Terapie Cellulari, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Anna Maria Raiola
- Ematologia e Terapie Cellulari, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Daniele Roberto Giacobbe
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Antonio Vena
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
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- Sabrina Beltramini
- Pharmacy Unit, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Bianca Bruzzone
- Department of Health Sciences, Hygiene Unit, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy
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- Roberto M Lemoli
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Emanuele Angelucci
- Ematologia e Terapie Cellulari, IRCCS Ospedale Policlinico San Martino , Genova , Italy
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- Matteo Bassetti
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa , Genoa , Italy
Description
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.</jats:p> </jats:sec>
Journal
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- Clinical Infectious Diseases
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Clinical Infectious Diseases 77 (2), 280-286, 2023-03-28
Oxford University Press (OUP)
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Details 詳細情報について
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- CRID
- 1360862099280267648
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- ISSN
- 15376591
- 10584838
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- Data Source
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- Crossref