Nirmatrelvir 150mg tablets

The high mutations of the Omicron variant of severe acute respiratory syndrome coronavirus 2 raised concerns regarding the efficacy of antivirals. This meta-analysis aimed to determine the impact of nirmatrelvir/ritonavir on the outcomes of immunocompetent patients with confirmed Omicron variant. Three reviewers systemically searched PubMed (Medline), Cochrane Library, and Embase databases up to June 9, 2025. Randomized clinical trials (RCTs) and observational studies with a control group were screened for eligibility to extract data. Studies that included only patients with immunosuppression, malignancy, or renal failure, severe disease, or assessed nirmatrelvir/ritonavir efficacy on variants other than Omicron were excluded. Forty-six observational studies, including 6,099,805 participants, were involved in the meta-analysis. Our findings revealed that nirmatrelvir/ritonavir significantly decreases death (risk ratio [RR] =0.31; 95% confidence interval [CI]: 0.23-0.40), disease progression (RR = 0.57; 95% CI: 0.42-0.71), hospitalization (RR = 0.45; 95% CI: 0.35-0.56), composite outcome of hospitalization and death (RR = 0.58; 95% CI: 0.44-0.71), ventilation (RR = 0.46; 95% CI: 0.19-0.72), and intensive care unit admission (RR = 0.56; 95% CI: 0.38-0.73) compared to the control group. However, no significant difference was shown across the two groups regarding hospitalization duration (mean difference = -2.34; 95% CI: -5.60-0.93). The current updated meta-analysis supported the efficacy of nirmatrelvir/ritonavir on the Omicron variant. However, further RCTs are recommended for accurate results.

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BackgroundThis study systematically synthesized existing evidence to evaluate whether outpatient treatment with nirmatrelvir/ritonavir during the acute phase reduces the incidence of long COVID.MethodsWe conducted a systematic search of Europe PMC, Medline, Scopus, and the Cochrane Library from inception to 15 September 2025. Eligible studies compared COVID-19 outpatients prescribed nirmatrelvir/ritonavir during the acute phase with those who did not receive the drug. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model.ResultsNineteen studies met inclusion criteria. Overall, nirmatrelvir/ritonavir use during acute infection was associated with a significant reduction in the likelihood of developing post-COVID-19 condition (OR 0.85; 95% CI: 0.80-0.91; p 2 = 99%). Protective effects were consistently observed across multiple clinical domains, including cardiovascular (arrhythmia, ischemic disease, heart failure), pulmonary (dyspnea, COPD), thromboembolic (DVT, PE), neurological (stroke, cognitive impairment, headache), psychiatric (depression), gastrointestinal, metabolic (new-onset diabetes), renal (AKI), and general symptoms (malaise and fatigue). Conversely, no significant differences were noted for cough, asthma, dysautonomia, anxiety, PTSD, sleep disturbances, musculoskeletal pain, or olfactory/gustatory dysfunction.ConclusionsEarly outpatient treatment with nirmatrelvir/ritonavir may mitigate the risk of developing several domains of long COVID, though its benefits are not uniform across all symptom categories.

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ObjectivesTo summarize individual patient data (IPD) on extended-duration nirmatrelvir-ritonavir (NMV-r) for persistent SARS-CoV-2 infection in immunocompromised adults and describe outcomes by regimen.MethodsWe conducted a systematic review with IPD synthesis (PRISMA-IPD; PROSPERO CRD42025642455), searching databases through December 2025 and restricting eligible reports to January 1, 2022, through December 31, 2025 (Omicron-era focus). IPD were obtained for 39 patients from four low-risk-of-bias cohort studies (n = 30) and institutional cases (n = 9) meeting predefined criteria for persistent infection. We summarized outcomes after last-line extended NMV-r and report exploratory, unadjusted subgroup descriptions for monotherapy (n = 27) and combination regimens (n = 12).ResultsMedian age was 63 years. Patients had prolonged viral replication (median 58 days) before receiving extended NMV-r (median 10 days). Persistent infection after last-line extended therapy occurred in 5/38 (13.2%) evaluable patients. Persistence was observed in 2/26 (7.7%) evaluable monotherapy and 3/12 (25.0%) combination-therapy recipients; because regimen selection was nonrandom and baseline risk differed between groups, these subgroup proportions are descriptive and should not be interpreted as comparative effectiveness. All-cause mortality and adverse events (AEs) were rare (each 1/39; 2.6%).ConclusionIn this selected observational IPD cohort, clearance after last-line extended NMV-r-containing therapy was commonly reported, and serious AEs were uncommon. Comparative inferences are limited by small sample size, imprecision, and confounding by indication; prospective studies are needed. PROSPERO registration CRD42025642455.

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BackgroundSince the benefit of nirmatrelvir-ritonavir (N-R) may have changed in contemporary patients, we assessed the effectiveness of N-R for preventing hospitalization and death among outpatients with COVID-19 in the Omicron era.MethodsThis was a meta-analysis of cohort studies comparing rates of hospitalization and/or mortality in outpatients treated with N-R compared with untreated patients. Analysis was limited to studies conducted since December 2021 that performed an adjusted multivariate analysis. Quality was assessed using the Newcastle-Ottawa Scale. Summary estimates of adjusted relative risks (aRR) with 95% confidence intervals (CI) and prediction intervals (PI) were calculated overall and for prespecified subgroups. Heterogeneity was summarized visually and with τ and 95% PIs. Absolute effects were estimated by applying pooled aRRs to baseline risks to obtain absolute risk reductions (ARRs) and numbers needed to treat (NNTs).ResultsForty-seven studies (10,791,211 patients) were included. Pooled aRRs were 0.54 (95% CI, 0.43-0.68) for all-cause hospitalization and 0.45 (0.36-0.56) for COVID-19 hospitalization. Pooled RRs were 0.30 (0.23-0.39) for all-cause mortality and 0.43 (0.32-0.59) for COVID-19 mortality. PIs were DiscussionN-R is associated with reduced hospitalization and death. Absolute risk reductions of hospitalization are small in low-risk patients but clinically meaningful in moderate- and high-risk patients.

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BackgroundNirmatrelvir-ritonavir is widely used for COVID-19, but effectiveness was established in unvaccinated people with SARS-CoV-2 variants before omicron. Within the randomised Platform Adaptive Trial of Novel Antivirals for Early Treatment of COVID-19 in the Community (PANORAMIC) trial, we did a substudy to evaluate virological and immunological outcomes.MethodsAdults (aged ≥50 years, or ≥18 years with comorbidities) with early COVID-19 were recruited across the UK in an open-label trial and randomly assigned to receive nirmatrelvir-ritonavir twice daily for 5 days plus usual care (nirmatrelvir-ritonavir group) or usual care alone (supportive treatment only with the use of antipyretics as required; usual care group). Before randomisation, participants were also invited to enter the virology substudy, and those who consented were sent swabs and blood spot testing kits for self-sampling with instructions. We performed viral quantitative PCR, viral culture, and sequencing on self-collected combined nasal and pharyngeal swabs submitted daily for 7 days and at day 14 (intensive sampling group) or at baseline, day 5, and day 14. We measured blood spot SARS-CoV-2 spike antibody titre and C-reactive protein (CRP) at baseline, day 5, and day 14 in all participants. We undertook mixed-effects modelling to identify predictors of viral load or spike antibody rate of change and assessed viral rebound by multiple definitions. The trial was registered with EudraCT, 2021-005748-31.FindingsFrom Sept 10, 2022, to Oct 23, 2023, 649 people agreed to participate in the virology substudy, of whom 27 were excluded per the prespecified analysis plan, resulting in 622 participants in the analysis: 326 in the nirmatrelvir-ritonavir group and 296 in the usual care group. Nirmatrelvir-ritonavir treatment reduced viral load from day 5 onwards and increased viral clearance. The estimated half-life was 0·78 days (95% CI 0·74-0·83) with usual care versus 0·66 days (95% CI 0·56-0·68) with nirmatrelvir-ritonavir; p10 U/mL [SD 0·48]), and baseline viral loads were low (mean 6·42 log10 copies per mL [1·49]) with the two correlating inversely (slope -0·63; pInterpretationNirmatrelvir-ritonavir is effectively antiviral against omicron SARS-CoV-2 variants, but the magnitude of viral load reduction might be limited by effective population-wide immunity in the immunocompetent population.FundingUK National Institute for Health and Care Research.

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Abstract Background While molnupiravir and nirmatrelvir-ritonavir have demonstrated efficacy in reducing hospitalisation and mortality among unvaccinated, high-risk COVID-19 patients in outpatient settings, their impact on hospitalised adults remains unclear. Preclinical studies and case reports suggest combining these antivirals may reduce viral shedding and enhance survival.Baseline characteristics of eligible COVID-19 patients after the inverse probability of treatment weighting (IPTW)SMD=Standardised mean difference; SD=Standard deviation; IQR = interquartile range; CCI=Charlson Comorbidity Index; ICU=Intensivecare units;†SMD<0.1 indicates balance between groups·†† Level 1: Hospitalised patients with no oxygen therapy; Level 2: Hospitalised patients with oxygen by mask, nasal prongs, non-invasiveventilation or high flow; Level 3: Hospitalised patients with intubation and mechanical ventilation, vasopressors, dialysis, or extracorporealmembrane oxygenationRisk of outcomes for COVID-19 patients receiving combined use of molnupiravir and nirmatrelvir ritonavir compared with patients receiving molnupiravir alone and patients receiving nirmatrelvir-ritonavir alone after weighting Methods This target trial emulation study evaluated the safety and efficacy of combined molnupiravir and nirmatrelvir-ritonavir versus monotherapy in hospitalised COVID-19 adults in Hong Kong. Data were extracted from electronic health records of patients aged 18 and older treated within five days of hospital admission between March 16, 2022, and March 31, 2024. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Outcomes, including all-cause mortality, Intensive Care Unit (ICU) admission, and ventilatory support, were assessed using Cox proportional hazards models.Study flow diagram90-day cumulative incidence of outcomes in recipients of combination treatment with nirmatrelvir-ritonavir and molnupiravir compared to recipients of molnupiravir monotherapy and recipients of nirmatrelvir-ritonavirShared area refers to the 95% confidence interval for the cumulative incidence. The P values indicate the overall P values of the Log-rank test comparing the three treatment groups for each outcome Results Among 28,355 patients (combination: 1,081; molnupiravir: 8,416; nirmatrelvir-ritonavir: 18,858), IPTW-adjusted analyses showed that nirmatrelvir-ritonavir monotherapy was associated with a significantly lower risk of mortality (HR: 0.62; 95% CI 0.50-0.77; ARR: -3.16%) compared to combination therapy. Risks of ICU admission and ventilatory support were similar across all groups. Patients receiving nirmatrelvir-ritonavir monotherapy also showed lower risks of acute liver injury (HR: 0.53 [95% CI 0.32-0.88]), acute kidney injury (HR: 0.61 [95% CI 0.51-0.74]), and hyperglycaemia (HR 0·73 [95% CI 0.57- 0.93]). Conclusion Combining nirmatrelvir-ritonavir and molnupiravir does not significantly reduce mortality, ICU admissions, or ventilatory support needs in hospitalised COVID-19 adults. Further randomised controlled trials are needed to confirm these findings. Disclosures All Authors: No reported disclosures

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