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

Clin Infect Dis. 2023 Jul 26;77(2):280-286. doi: 10.1093/cid/ciad181.

Abstract

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.

Keywords: anti-CD20 treatment; anti–SARS-CoV-2 monoclonal antibodies; lymphoma; nirmatrelvir/ritonavir; remdesivir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal* / therapeutic use
  • Antibodies, Neutralizing* / therapeutic use
  • Antiviral Agents* / therapeutic use
  • COVID-19 Drug Treatment* / adverse effects
  • COVID-19 Drug Treatment* / methods
  • COVID-19*
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunocompromised Host*
  • Male
  • Middle Aged
  • Recurrence
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Antibodies, Monoclonal
  • cilgavimab and tixagevimab drug combination
  • Drug Combinations
  • Antibodies, Neutralizing