Infectious Diseases and Therapy (Jun 2024)

Clinical Outcome and 7-Day Virological Clearance in High-Risk Patients with Mild–Moderate COVID-19 Treated with Molnupiravir, Nirmatrelvir/Ritonavir, or Remdesivir

  • Francesca Bai,
  • Tomaso Beringheli,
  • Virginia Vitaletti,
  • Andrea Santoro,
  • Francesco Molà,
  • Alessandro Copes,
  • Nicole Gemignani,
  • Sofia Pettenuzzo,
  • Roberto Castoldi,
  • Benedetta Varisco,
  • Riccardo Nardo,
  • Lorenzo Brando Lundgren,
  • Riccardo Ligresti,
  • Matteo Sala,
  • Lorenzo Albertini,
  • Matteo Augello,
  • Lorenzo Biasioli,
  • Valeria Bono,
  • Roberta Rovito,
  • Teresa Bini,
  • Sabrina Passarella,
  • Nicola Vincenzo Orfeo,
  • Antonella d’Arminio Monforte,
  • Giulia Marchetti

DOI
https://doi.org/10.1007/s40121-024-00994-3
Journal volume & issue
Vol. 13, no. 7
pp. 1589 – 1605

Abstract

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Abstract Introduction We compared the effectiveness and virological clearance (VC) at day 7 (T7) post-treatment with molnupiravir, nirmatrelvir/ritonavir, and remdesivir in SARS-CoV-2-infected patients at high risk (HR) for clinical progression. Methods We conducted a retrospective study enrolling HR patients with mild-to-moderate COVID-19 (Jan–Oct 2022) treated with nirmatrelvir/ritonavir or molnupiravir or 3 days of remdesivir. We investigated clinical recovery at T7 (resolution of symptoms for ≥ 72 h or all-cause death), VC at T7 (PCR/antigenic negative nasopharyngeal swab), and median time to VC (days from symptom onset to the first negative swab). Factors associated with VC were investigated by logistic regression. Results In the study, 92/376 (43.8%) patients received molnupiravir, 150/376 (24.7%) nirmatrelvir/ritonavir, and 134/376 (31.5%) remdesivir. Forty-nine (13%) patients were unvaccinated or incompletely vaccinated. Patients treated with nirmatrelvir/ritonavir were younger and presented immunodeficiencies more frequently; remdesivir was used more commonly in patients hospitalized for other diseases. A high proportion of patients obtained clinical recovery without differences among the therapies (97.5% for molnupiravir, 98.3% for nirmatrelvir/ritonavir, and 93.6% for remdesivir); 12 (3.7%) patients died. Nirmatrelvir/ritonavir was associated with a higher proportion of T7 VC and a shorter time to VC compared to molnupiravir/remdesivir, also after adjustment for age and immunodeficiency (AOR 0.445 RDV vs. NMV-r, 95% CI 0.240–0.826, p = 0.010; AOR 0.222 MNP vs. NMV-r, 95% CI 0.105–0.472, p < 0.001). Conclusions SARS-COV-2 antiviral treatments are an excellent therapeutic strategy in HR patients. Nirmatrelvir/ritonavir showed a higher proportion of VC as early as 7 days after treatment, confirming its likely superiority in indirect comparisons.

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