| Title: |
Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients |
| Authors: |
Mikulska, Malgorzata; Sepulcri, Chiara; Dentone, Chiara; Magne, Federica; Balletto, Elisa; Baldi, Federico; Labate, Laura; Russo, Chiara; Mirabella, Michele; Magnasco, Laura; Di Grazia, Carmen; Ghiggi, Chiara; Raiola, Anna Maria; Giacobbe, Daniele Roberto; Vena, Antonio; Beltramini, Sabrina; Bruzzone, Bianca; Lemoli, Roberto M; Angelucci, Emanuele; Bassetti, Matteo |
| Source: |
Clinical Infectious Diseases ; volume 77, issue 2, page 280-286 ; ISSN 1058-4838 1537-6591 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/cid/ciad181 |
| DOI: |
10.1093/cid/ciad181/50112784/ciad181.pdf |
| Availability: |
https://doi.org/10.1093/cid/ciad181; https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciad181/50112784/ciad181.pdf; https://academic.oup.com/cid/article-pdf/77/2/280/50968823/ciad181.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.D87B5478 |
| Database: |
BASE |