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] |
---|
Links: |
---|
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 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM354813005 | ||
003 | DE-627 | ||
005 | 20231226063025.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1093/cid/ciad181 |2 doi | |
028 | 5 | 2 | |a pubmed24n1182.xml |
035 | |a (DE-627)NLM354813005 | ||
035 | |a (NLM)36976301 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Mikulska, Malgorzata |e verfasserin |4 aut | |
245 | 1 | 0 | |a Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 09.11.2023 | ||
500 | |a Date Revised 09.11.2023 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 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. | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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) | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a anti-CD20 treatment | |
650 | 4 | |a anti–SARS-CoV-2 monoclonal antibodies | |
650 | 4 | |a lymphoma | |
650 | 4 | |a nirmatrelvir/ritonavir | |
650 | 4 | |a remdesivir | |
650 | 7 | |a Antiviral Agents |2 NLM | |
650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
650 | 7 | |a cilgavimab and tixagevimab drug combination |2 NLM | |
650 | 7 | |a Drug Combinations |2 NLM | |
650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
700 | 1 | |a Sepulcri, Chiara |e verfasserin |4 aut | |
700 | 1 | |a Dentone, Chiara |e verfasserin |4 aut | |
700 | 1 | |a Magne, Federica |e verfasserin |4 aut | |
700 | 1 | |a Balletto, Elisa |e verfasserin |4 aut | |
700 | 1 | |a Baldi, Federico |e verfasserin |4 aut | |
700 | 1 | |a Labate, Laura |e verfasserin |4 aut | |
700 | 1 | |a Russo, Chiara |e verfasserin |4 aut | |
700 | 1 | |a Mirabella, Michele |e verfasserin |4 aut | |
700 | 1 | |a Magnasco, Laura |e verfasserin |4 aut | |
700 | 1 | |a Di Grazia, Carmen |e verfasserin |4 aut | |
700 | 1 | |a Ghiggi, Chiara |e verfasserin |4 aut | |
700 | 1 | |a Raiola, Anna Maria |e verfasserin |4 aut | |
700 | 1 | |a Giacobbe, Daniele Roberto |e verfasserin |4 aut | |
700 | 1 | |a Vena, Antonio |e verfasserin |4 aut | |
700 | 1 | |a Beltramini, Sabrina |e verfasserin |4 aut | |
700 | 1 | |a Bruzzone, Bianca |e verfasserin |4 aut | |
700 | 1 | |a Lemoli, Roberto M |e verfasserin |4 aut | |
700 | 1 | |a Angelucci, Emanuele |e verfasserin |4 aut | |
700 | 1 | |a Bassetti, Matteo |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Clinical infectious diseases : an official publication of the Infectious Diseases Society of America |d 1992 |g 77(2023), 2 vom: 26. Juli, Seite 280-286 |w (DE-627)NLM012603007 |x 1537-6591 |7 nnns |
773 | 1 | 8 | |g volume:77 |g year:2023 |g number:2 |g day:26 |g month:07 |g pages:280-286 |
856 | 4 | 0 | |u http://dx.doi.org/10.1093/cid/ciad181 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 77 |j 2023 |e 2 |b 26 |c 07 |h 280-286 |