Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:77

Enthalten in:

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 77(2023), 2 vom: 26. Juli, Seite 280-286

Sprache:

Englisch

Beteiligte Personen:

Mikulska, Malgorzata [VerfasserIn]
Sepulcri, Chiara [VerfasserIn]
Dentone, Chiara [VerfasserIn]
Magne, Federica [VerfasserIn]
Balletto, Elisa [VerfasserIn]
Baldi, Federico [VerfasserIn]
Labate, Laura [VerfasserIn]
Russo, Chiara [VerfasserIn]
Mirabella, Michele [VerfasserIn]
Magnasco, Laura [VerfasserIn]
Di Grazia, Carmen [VerfasserIn]
Ghiggi, Chiara [VerfasserIn]
Raiola, Anna Maria [VerfasserIn]
Giacobbe, Daniele Roberto [VerfasserIn]
Vena, Antonio [VerfasserIn]
Beltramini, Sabrina [VerfasserIn]
Bruzzone, Bianca [VerfasserIn]
Lemoli, Roberto M [VerfasserIn]
Angelucci, Emanuele [VerfasserIn]
Bassetti, Matteo [VerfasserIn]

Links:

Volltext

Themen:

Anti–SARS-CoV-2 monoclonal antibodies
Anti-CD20 treatment
Antibodies, Monoclonal
Antibodies, Neutralizing
Antiviral Agents
Cilgavimab and tixagevimab drug combination
Drug Combinations
Journal Article
Lymphoma
Nirmatrelvir/ritonavir
Remdesivir
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 09.11.2023

Date Revised 09.11.2023

published: Print

Citation Status MEDLINE

doi:

10.1093/cid/ciad181

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM354813005