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. 2024 Jul;13(7):1589-1605.
doi: 10.1007/s40121-024-00994-3. Epub 2024 Jun 3.

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  1 , Tomaso Beringheli  2 , Virginia Vitaletti  2 , Andrea Santoro  2 , Francesco Molà  2 , Alessandro Copes  2 , Nicole Gemignani  2 , Sofia Pettenuzzo  2 , Roberto Castoldi  2 , Benedetta Varisco  2 , Riccardo Nardo  2 , Lorenzo Brando Lundgren  2 , Riccardo Ligresti  2 , Matteo Sala  2 , Lorenzo Albertini  2 , Matteo Augello  2 , Lorenzo Biasioli  2 , Valeria Bono  2 , Roberta Rovito  2 , Teresa Bini  2 , Sabrina Passarella  3 , Nicola Vincenzo Orfeo  3 , Antonella d'Arminio Monforte  2 , Giulia Marchetti  2
Affiliations

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 et al. Infect Dis Ther. 2024 Jul.

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.

Keywords: Antiviral SARS CoV-2 treatment; COVID-19; Molnupiravir; Nirmatrelvir/ritonavir; Remdesivir.

Plain language summary

Nirmatrelvir-ritonavir, molnupiravir, and a 3-day course of remdesivir are antiviral therapies recommended in patients with a mild-to-moderate COVID-19 disease at high risk of clinical progression. Randomized controlled trials and observational studies have shown their efficacy in reducing all-cause mortality and clinical progression. Few data are available about a direct comparison among the three drugs; furthermore, the possible role of nirmatrelvir-ritonavir in increasing viral clearance and in reducing the duration of viral shedding needs to be further elucidated. We thus investigated the effectiveness, safety, and virological clearance 7 days after treatment with these three antivirals in our retrospective cohort. We included in the analysis patients that have received these treatments from January 2022 and October 2022; we observed that patients receiving nirmatrelvir-ritonavir displayed a shorter median time from symptoms’ onset to virological clearance and a higher proportion of virological clearance at day 7, also after adjustment for possible confounders, compared to molnupiravir and remdesivir. Our data might help in understanding which COVID-19 patients may benefit mostly from antiviral therapies and in the choice of antiviral therapy.

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Conflict of interest statement

Francesca Bai, Tomaso Beringheli, Virginia Vitaletti, Andrea Santoro, Francesco Molà, Alessandro Copes, Nicole Gemignani, Sofia Pettenuzzo, Roberto Castoldi, Benedetta Varisco, 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, and Giulia Marchetti declare that the research was conducted in the absence of any commercial or financial relationships that could be interpreted as a potential conflict of interest.

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