Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study

Gentile, Ivan; Scotto, Riccardo; Moriello, Nicola Schiano; Pinchera, Biagio; Villari, Riccardo; Trucillo, Emilia; Ametrano, Luigi; Fusco, Ludovica; Castaldo, Giuseppe; Buonomo, Antonio Riccardo

doi:10.1101/2022.08.23.22278585

Cited by 23 publications

(8 citation statements)

References 27 publications

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“…negative conversion time was significantly shorter in Paxlovidtreated patients compared to nontreated patients. In comparison with molnupiravir, Paxlovid treatment led to a shorter duration of PCR-negative conversion time in patients with mild-to-moderate COVID-19 19. The present results showed no significant advantage in the use of Paxlovid in COVID-19 patients compared to the no-Paxlovid group in terms of ICU admission.…”

contrasting

confidence: 53%

“…Finally, 37 studies were eligible for review by full text. Twenty-three studies [6][7][8][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] involving 314 353 patients were included in the meta-analysis. All included studies except one 7 were retrospective.…”

Section: Search Resultsmentioning

confidence: 99%

“…The pooled estimate of 11 studies 6,7,[17][18][19]22,27,28,30,32,34 involving hospitalization rate of Paxlovid-treated patients and the no-Paxlovid group (OR = 0.40; 95% CI: 0.24-0.69; p = 0.001) (Figure 2B).…”

Section: Hospitalization Ratementioning

confidence: 99%

“…The pooled estimate of seven studies 15,16,19,21,26,31,33 involving 1187 patients showed a significant difference between the Paxlovid and no-Paxlovid groups in terms of PCR-negative conversion time (MD = −2.46; 95% CI: −4.31 to −0.61; p = 0.009) (Figure 2D).…”

Section: Pcr-negative Conversion Timementioning

confidence: 99%

“…The results of the risk of bias in the included studies are shown in Supporting Information: Tables S1 and S2. Thirteen studies [6][7][8][17][18][19][20][22][23][24][25]29,34 involving 298 913 patients were included in the meta-analysis. The pooled estimate showed a significant difference in the mortality rate of Paxlovid-recieving patients compared to those who not received Paxlovid (OR = 0.25; 95% CI: 0.14-0.45; p = 0.000) (Figure 2A).…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

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Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID‐19: A rapid review and meta‐analysis

Amani

2023

Journal of Medical Virology

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This study aimed to examine the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for coronavirus disease 2019 (COVID‐19). PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar were searched to identify the relevant evidence up to November 10, 2022. The reference lists of key studies were also scanned to find additional records. The quality of the studies was evaluated using the Cochrane tools for assessing the risk of bias. The Comprehensive Meta‐Analysis software version 3.0 was employed for data analysis. Twenty‐three studies involving 314 353 patients were included in the analysis. The findings of the meta‐analysis showed a significant difference between the Paxlovid and no‐Paxlovid groups in terms of mortality rate (odds ratio [OR] = 0.25; 95% confidence interval [CI]: 0.14–0.45), hospitalization rate (OR = 0.40; 95% CI: 0.24–0.69), polymerase chain reaction negative conversion time (mean difference [MD] = −2.46; 95% CI: −4.31 to −0.61), and hospitalization or death rate (OR = 0.17; 95% CI: 0.06–0.46). However, no significant difference was observed between the two groups in terms of COVID‐19 rebound (OR = 0.84; 95% CI: 0.67–1.04), emergency department visit (OR = 0.75; 95% CI: 0.45–1.24), intensive care unit admission (OR = 0.37; 95% CI: 0.13–1.01), and adverse events (OR = 2.20; 95% CI: 0.42–11.47). The results of the present study support the efficacy and safety of Paxlovid in the treatment of patients with COVID‐19. Further research is needed to investigate the COVID‐19 rebound after Paxlovid treatment.

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contrasting

confidence: 53%

Section: Search Resultsmentioning

confidence: 99%

Section: Hospitalization Ratementioning

confidence: 99%

Section: Pcr-negative Conversion Timementioning

confidence: 99%

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

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Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID‐19: A rapid review and meta‐analysis

Amani

2023

Journal of Medical Virology

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Real-World Effectiveness of Nirmatrelvir/Ritonavir on Covid-19-Associated Hospitalization Prevention: A Population-Based Cohort Study in the Province of Québec, Canada

Kaboré

Laffont

Diop

et al. 2023

Preprint

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Introduction The nirmatrelvir/ritonavir (PAXLOVIDTM) is an antiviral blocking the replication of SARS-CoV-2. Early treatment with this antiviral has showed to reduce COVID-19 hospitalization and death in unvaccinated outpatients with mild-to-moderate COVID-19 and high risk of progression to severe disease with variants before Omicron. However, the current epidemiological context and the level of immunity in the population (vaccination and/or natural infection) have evolved considerably since the disclosure of these results. Thus, real-world evidence studies in vaccinated outpatients with lineage and sublineage of the variant are needed. Objective To assess whether nirmatrelvir/ritonavir treatment reduces the risk of COVID-19-associated hospitalization among Québec outpatients with mild-to-moderate COVID-19 at high risk of progression to severe disease in a real-world context, regardless of vaccination status and circulating variants, in the province of Québec. Methods This was a retrospective cohort study of SARS-CoV-2-infected outpatients who received nirmatrelvir/ritonavir between March 15 and August 15, 2022, using data from the Québec provincial clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared to unexposed ones. The treatment group was matched with controls using propensity-score matching in a ratio of 1:1. The outcome was COVID-19-associated hospitalization occurring within 30 days following the index date. Poisson regression with robust error variance was used to estimate the relative risk of hospitalization among the treatment group compared to the control group. Results A total of 16,601 and 242,341 outpatients were eligible to be included in the treatment (nirmatrelvir/ritonavir) and control groups respectively. Among treated outpatients, 8,402 were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir-treated outpatient status was associated with a 69% reduced relative risk of COVID-19-associated hospitalization (RR: 0.31 [95% CI: 0.28; 0.36]). The effect was more pronounced in outpatients without a complete primary vaccination course (RR: 0.04 [95% CI: 0.03; 0.06]), while treatment with nirmatrelvir/ritonavir was not associated with benefit when outpatients with a complete primary vaccination course were considered (RR: 0.93 [95% CI: 0.78; 1.08]) Subgroups analysis among outpatients with a primary vaccination course showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in relative risk of hospitalization in severely immunocompromised outpatients (RR: 0.66 [95% CI: 0.50; 0.89]) and in outpatients aged 70 years and older (RR: 0.50 [95% CI: 0.34; 0.74]) when the last dose of the vaccine was received more than six months before. Conclusions Among SARS-CoV-2 infected outpatients at high risk for severe COVID-19 during Omicron BA.2 and BA.4/5 surges, treatment with nirmatrelvir/ritonavir was associated with a significant reduced relative risk of COVID-19-associated hospitalization. This effect was observed in outpatients with incomplete primary vaccination course and in outpatients who were severely immunocompromised. Except for severely immunocompromised outpatients, no evidence of benefit was found in any category of outpatient with a complete primary vaccination course whose last dose of COVID-19 vaccine was received within six months.

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SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in mice

Alhammad

Parthasarathy

Ghimire

et al. 2023

Preprint

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Several coronavirus (CoV) encoded proteins are being evaluated as targets for antiviral therapies for COVID-19. Included in this set of proteins is the conserved macrodomain, or Mac1, an ADP-ribosylhydrolase and ADP-ribose binding protein. Utilizing point mutant recombinant viruses, Mac1 was shown to be critical for both murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV virulence. However, as a potential drug target, it is imperative to understand how a complete Mac1 deletion impacts the replication and pathogenesis of different CoVs. To this end, we created recombinant bacterial artificial chromosomes (BACs) containing complete Mac1 deletions (ΔMac1) in MHV, MERS-CoV, and SARS-CoV-2. While we were unable to recover infectious virus from MHV or MERS-CoV ΔMac1 BACs, SARS-CoV-2 ΔMac1 was readily recovered from BAC transfection, indicating a stark difference in the requirement for Mac1 between different CoVs. Furthermore, SARS-CoV-2 ΔMac1 replicated at or near wild-type levels in multiple cell lines susceptible to infection. However, in a mouse model of severe infection, ΔMac1 was quickly cleared causing minimal pathology without any morbidity. ΔMac1 SARS-CoV-2 induced increased levels of interferon (IFN) and interferon-stimulated gene (ISG) expression in cell culture and mice, indicating that Mac1 blocks IFN responses which may contribute to its attenuation. ΔMac1 infection also led to a stark reduction in inflammatory monocytes and neutrophils. These results demonstrate that Mac1 only minimally impacts SARS-CoV-2 replication, unlike MHV and MERS-CoV, but is required for SARS-CoV-2 pathogenesis and is a unique antiviral drug target.

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Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study

Cited by 23 publications

References 27 publications

Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID‐19: A rapid review and meta‐analysis

Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID‐19: A rapid review and meta‐analysis

Real-World Effectiveness of Nirmatrelvir/Ritonavir on Covid-19-Associated Hospitalization Prevention: A Population-Based Cohort Study in the Province of Québec, Canada

SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in mice

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