Early combination of sotrovimab with nirmatrelvir/ritonavir or remdesivir is associated with low rate of persisting SARS CoV-2 infection in immunocompromised outpatients with mild-to-moderate COVID-19: a prospective single-centre study

Ann Med. 2025 Dec;57(1):2439541. doi: 10.1080/07853890.2024.2439541. Epub 2024 Dec 11.

Abstract

Background: Immunocompromised patients are at high risk of developing persisting/prolonged COVID-19. Data on the early combined use of antivirals and monoclonal antibodies in this population are scarce.

Research design and methods: We performed an observational, prospective study, enrolling immunocompromised outpatients with mild-to-moderate COVID-19, treated with a combination of sotrovimab plus one antiviral (remdesivir or nirmatrelvir/ritonavir) within 7 days from symptom onset. Primary outcome was hospitalization within 30 days. Secondary outcomes were: needing for oxygen therapy; development of persistent infection; death within 60 days and reinfection or relapse within 90 days.

Results: We enrolled 52 patients. No patient was hospitalized within 30 days of disease onset, required oxygen administration, died within 60 days, or experienced a reinfection or clinical relapse within 90 days.The clearance rates were 67% and 97% on the 14th day after the end of therapy and at the end of the follow-up period, respectively.Factors associated with longer infection were initiation of therapy 3 days after symptom onset and enrollment for more than 180 days from the beginning of the study. However, only the latter factor was independently associated with a longer SARS-CoV-2 infection, suggesting a loss of efficacy of this strategy with the evolution of SARS-CoV-2 variants.

Conclusions: Early administration of combination therapy with a direct antiviral and sotrovimab seems to be effective in preventing hospitalization, progression to severe COVID-19, and development of prolonged/persisting SARS-CoV-2 infection in immunocompromised patients.

Keywords: COVID-19; combination; immunocompromised; nirmatrelvir; remdesivir; sotrovimab.

Publication types

  • Observational Study

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine Monophosphate* / administration & dosage
  • Adenosine Monophosphate* / analogs & derivatives
  • Adenosine Monophosphate* / therapeutic use
  • Adult
  • Aged
  • Alanine* / administration & dosage
  • Alanine* / analogs & derivatives
  • Alanine* / therapeutic use
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antiviral Agents* / administration & dosage
  • Antiviral Agents* / therapeutic use
  • COVID-19 / mortality
  • COVID-19 Drug Treatment*
  • Drug Therapy, Combination*
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Immunocompromised Host*
  • Leucine / administration & dosage
  • Leucine / analogs & derivatives
  • Leucine / therapeutic use
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / therapeutic use
  • Ritonavir* / administration & dosage
  • Ritonavir* / therapeutic use
  • SARS-CoV-2*
  • Treatment Outcome
  • Uracil / administration & dosage
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use

Substances

  • Ritonavir
  • Alanine
  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Antibodies, Monoclonal, Humanized
  • GS-441524
  • Pyrrolidines
  • Leucine
  • Uracil
  • Adenosine

Grants and funding

This research was supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project No. PE00000007, INF-ACT). Ivan Gentile and Giulio Viceconte are the main recipients of the public funding.