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Paxlovid for COVID-19
89 studies with >170,000 patients
Serious outcome risk
Paxlovid
Control
Pfizer RCTs report very good results, while non-Pfizer RCT results are relatively poor, and Pfizer has denied access for other independent RCTs. An FDA black box warning notes that drug interactions may result in severe, life-threatening, and/or fatal adverse reactions. Studies show significantly increased risk of acute kidney injury, liver injury, and replication-competent viral rebound.
COVID-19 Paxlovid studies · October 2026
Pfizer has denied access to paxlovid for independent RCTs1. Pfizer RCTs report very good results, while non-Pfizer RCTs show relatively poor results2,3. Variants may be resistant to paxlovid4-12. Hoertel et al. find that >50% of patients that died had a contraindication for paxlovid. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy. Black box warning. The FDA notes that severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid14. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID15. Population studies often do not account for the different expected outcomes for the class of patients that seek out and receive early treatment. Studies show significantly increased risk of acute kidney injury16, liver injury17,18, and replication-competent viral rebound19-21. Paxlovid is a combination of nirmatrelvir and ritonavir. Nirmatrelvir is a first generation SARS-CoV-2 3CL protease inhibitor22. Ritonavir is a HIV drug used to boost the levels of nirmatrelvir in the body by inhibiting its metabolism. Paxlovid was adopted in 64 countries. Recent:
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Covid Analysis Meta-analysis of paxlovid studies
Meta-analysis of paxlovid studies
Aug 16
 How et al., International Journal of Molecular Sciences, doi:10.3390/ijms27167316 The Combination of Nirmatrelvir and Ivermectin Exerts Strongly Synergistic Antiviral and Anti-Inflammatory Effects Against Murine Coronavirus Infection of Macrophages
In vitro study showing strong synergistic antiviral and anti-inflammatory effects with the combination of ivermectin and nirmatrelvir for RAW264.7 murine macrophages infected with murine hepatitis virus (MHV). The combination achieved at ..
Jun 30
 Liu et al., The Journal of Infection in Developing Countries, doi:10.3855/jidc.21811 Association between Paxlovid and mortality in severe COVID-19 patients: a retrospective cohort study
Retrospective 1,219 hospitalized severe COVID-19 patients in China showing significantly lower 28-day mortality with paxlovid. This study has several serious issues: Immortal-time bias: follow-up began at hospital admission, but paxlovid ..
Jun 3
 Khoo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkag180 A randomized controlled Phase I de-escalation trial of molnupiravir and nirmatrelvir/ritonavir combination for mild-moderate SARS-CoV-2 infection
Phase I RCT of 24 outpatients (16 combination therapy, 8 standard of care) showing that molnupiravir (800 mg twice daily) combined with nirmatrelvir/ritonavir (300/100 mg twice daily) for 5 days was safe and well-tolerated in mild-to-mode..
Jun 2
 Kueper et al., Interactive Journal of Medical Research, doi:10.2196/80263 COVID-19 Rebound in Nirmatrelvir Plus Ritonavir Treatment and Control Groups: Prospective Cohort Study
87% worse recovery (p=0.02) and 148% worse viral clearance (p=0.01). Prospective observational study of 669 COVID-19 outpatients in the USA showing higher rates of viral and symptom rebound with paxlovid.
May 29
 Liu et al., Medicine, doi:10.1097/MD.0000000000049099 Independent mortality predictors in older COVID-19 patients with delayed hospitalization: A retrospective study from Eastern China, 2023
Retrospective 300 elderly hospitalized COVID-19 patients in China, showing no mortality benefit with antivirals (paxlovid and molnupiravir) in multivariable analysis, OR 1.15 [0.28-4.74], without statistical significance.
Apr 27
 Chen et al., Journal of Virology, doi:10.1128/jvi.02223-25 SARS-CoV-2 3CLpro mutations T21I and E166A confer differential resistance to simnotrelvir, bofutrelvir, and ensitrelvir
In vitro and mouse study showing differential resistance of SARS-CoV-2 3CLpro T21I/E166A mutations to simnotrelvir, bofutrelvir, nirmatrelvir, and ensitrelvir. The resistant isolate SARS2-T21I/E166A showed 4.3-9.2-fold resistance to simno..
Mar 27
 Zimmerman et al., NCT05965726 RECOVER-VITAL: A Platform Protocol for Evaluation of Interventions for Viral Persistence, Viral Reactivation, and Immune Dysregulation in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
9% worse improvement (p=0.22). RCT 964 patients showing no difference in improvement of long COVID with 15-day or 25-day paxlovid compared with placebo. Results appeared in the registry 15 months after primary completion, with no publication or announcement [clinicaltr..
Mar 24
 Azhir et al., Communications Medicine, doi:10.1038/s43856-026-01535-4 Paxlovid shows organ-specific and age-specific impacts on risk of developing post-acute sequelae of COVID-19
7% higher long COVID (p=0.29). Retrospective 19,413 COVID-19 outpatient and hospitalized patients showing no overall reduction in long COVID risk with paxlovid. Stratification by organ system found a 37% reduction in gastrointestinal PASC (OR 0.63, p=0.002) - biologica..
Mar 19
 Mokgokong et al., Health and Quality of Life Outcomes, doi:10.1186/s12955-026-02518-8 Health-related quality of life in immunocompromised adults with mild–moderate COVID-19 treated with nirmatrelvir-ritonavir: results from the randomized, double-blinded EPIC-IC trial
RCT 150 immunocompromised adults with mild-to-moderate COVID-19 comparing 5, 10, or 15 days of nirmatrelvir/ritonavir. There was no control group. No dose-response relationship was observed: HRQoL recovery patterns were statistically..
Mar 17
 Guo et al., BMC Medicine, doi:10.1186/s12916-026-04791-2 Effectiveness of nirmatrelvir/ritonavir and molnupiravir on post-COVID diabetes risk among an older adult cohort: a target trial emulation study
Retrospective analysis finding lower risk of post-COVID diabetes with nirmatrelvir/ritonavir but not molnupiravir. The effect may be entirely due to confounding. Authors excluded only 8% of non-diabetic patients for nirmatrelvir/ritonavir..
Mar 10
 Zhu et al., Scientific Reports, doi:10.1038/s41598-026-42215-6 A real-world retrospective analysis comparing the effectiveness of Azvudine and Nirmatrelvir/Ritonavir in COVID-19 patients with diabetes
Retrospective study of 400 hospitalized COVID-19 patients with diabetes in China showing no significant difference in the composite endpoint of disease progression (all-cause mortality, ICU admission, or invasive mechanical ventilation) b..
Mar 10
 Chu et al., Frontiers in Public Health, doi:10.3389/fpubh.2026.1760355 Analysis of Long COVID characteristics and risk factors in individuals infected with COVID-19: a follow-up study based on a cohort of 2,792 participants
10% higher long COVID (p=0.83). Prospective study of 2,792 COVID-19 patients in China. After propensity score matching, neither paxlovid nor azvudine showed a statistically significant association with long COVID.
Feb 26
 Bhattacharjee et al., medRxiv, doi:10.64898/2026.02.24.26347001 Exploratory analyses of Immunologic Features in a Randomized, Placebo-Controlled Trial of Nirmatrelvir/Ritonavir for Long COVID
RCT 82 long COVID patients showing no significant differences with nirmatrelvir/ritonavir treatment. The study found no improvement in physical health summary scores, no changes in circulating SARS-CoV-2 spike protein levels, and no signi..
Feb 11
 Astorga et al., Frontiers in Public Health, doi:10.3389/fpubh.2026.1698604 Canadian adaptive platform trial of treatments for COVID in community settings (CanTreatCOVID): recruitment strategies of a decentralized, national randomized controlled trial for acute SARS-CoV-2
Recruitment strategy analysis for the decentralized adaptive platform trial CanTreatCOVID. This is the second paper published reporting secondary analyses, while authors have not yet published the actual efficacy results of the trial.
Jan 30
 Chen et al., Acta Cardiol Sin, doi:10.6515/ACS.202601_42(1).20250726A Cardiovascular Outcomes in COVID-19 Patients Treated with Paxlovid: A Multicenter Retrospective Study
11% lower mortality (p=0.21). Retrospective 606 COVID-19 patients treated with paxlovid and 1,809 propensity score-matched controls in Taiwan, showing short-term mortality benefits at 3 months, but reduced benefit at 6 months, and no significant benefit at 12 months. ..
Jan 28
 Hosseini et al., medRxiv, doi:10.64898/2026.01.23.26343617 Balancing data quality and participant burden: A comparative analysis of abbreviated vs extended symptom diaries in the CanTreatCOVID trial
Secondary analysis of the CanTreatCOVID paxlovid RCT comparing adherence and symptom reporting between a 9-item abbreviated diary and 34-item FLU-PRO Plus diary in 712 COVID-19 outpatients, showing no significant difference in compliance,..
Jan 11
 Siby et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf695.1825 Temporal Trends in Serious Adverse Events Associated with Oral Antivirals During the COVID-19 Pandemic: Insights from the FAERS Database (2020–2023)
Retrospective 11,547 serious adverse event reports from the FDA database (2020-2023) showing significant safety signals with oral COVID-19 antivirals. Paxlovid showed the strongest signals for drug-drug interactions (ROR: 4.83) and liver ..
Jan 11
 Campion et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf695.1809 Disparities in the Use of nirmatrelvir/ritonavir for COVID-19: A Retrospective Cohort Study
Retrospective 3,498 patients receiving COVID-19 antivirals showing that female patients were significantly more likely to receive treatment. Studies show that female patients are significantly more likely to be "health-conscious"..
Jan 11
 Hong Choi et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf695.1812 Comparative Effectiveness of Combination Therapy with Nirmatrelvir-Ritonavir and Molnupiravir versus Monotherapy with Molnupiravir or Nirmatrelvir-Ritonavir in Hospitalised COVID-19 Patients: A Target Trial Emulation Study
3% lower mortality (p=0.8), 21% lower ventilation (p=0.39), and 28% higher ICU admission (p=0.46). IPTW retrospective target trial emulation of 28,355 hospitalized COVID-19 patients in Hong Kong showing no benefit and potential harm (higher mortality) with combined nirmatrelvir-ritonavir and molnupiravir compared to nirmatrelvir-ritona..
Jan 10
 Prager et al., Virology Journal, doi:10.1186/s12985-025-03057-2 Viral kinetics in adults with Covid-19 treated with nirmatrelvir-ritonavir or molnupiravir: a population-based, observational cohort study
22% worse viral clearance (p<0.0001). Observational cohort study of 113,399 COVID-19 outpatients in Vienna showing viral kinetics patterns with nirmatrelvir-ritonavir and molnupiravir treatment. Both antivirals showed improved viral clearance at 7 days, but worse viral cleara..
Jan 9
 Shah et al., The Lancet Microbe, doi:10.1016/j.lanmic.2025.101227 SARS-CoV-2 infectious shedding and rebound among adults with and without oral antiviral use: two case-ascertained prospective household studies
218% worse results (p=0.01). Prospective study of 160 non-hospitalized adults at high risk for severe COVID-19 showing paxlovid or molnupiravir associated with increased risk of viral rebound with infectious virus. Among treated participants, 25% experienced culture ..
Jan 8
 Lin et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiag026 Incidence and Severity of Postacute Sequelae of SARS-CoV-2 Infection in the Omicron Era: A Prospective Cohort Study
Prospective study of 2,960 nonhospitalized adults in the USA showing no significant difference in long-COVID with antiviral therapy using paxlovid or molnupiravir, aHR 1.02, 95% CI 0.87-1.21.
Jan 5
 Pridgen et al., Frontiers in Immunology, doi:10.3389/fimmu.2025.1698271 Patient-reported improvements from use of IMC-2 alone and IMC-2 and Paxlovid® in a Long COVID cohort: a case series
Case series of 24 long COVID outpatients showing greater symptom improvement with a combination of IMC-2 (valacyclovir + celecoxib) plus 15-day paxlovid compared to IMC-2 alone over 120 days.
Dec 31
2025
 Tong et al., NCT04483960 A Multi-centre Randomised Adaptive Platform Clinical Trial to Assess Clinical, Virological and Immunological Outcomes in Patients With SARS-CoV-2 Infection (COVID-19)
Estimated 2,200 patient paxlovid late treatment RCT with results not reported over 9 months after estimated completion.
Oct 14
2025
 Mokgokong et al., Infectious Diseases and Therapy, doi:10.1007/s40121-025-01228-w Symptom Alleviation/Resolution and Returns to Usual Health/Activities in Immunocompromised Adults with COVID-19 Treated with Nirmatrelvir-Ritonavir: Results from the EPIC-IC Trial
RCT 156 immunocompromised COVID-19 patients comparing 5-day, 10-day, and 15-day paxlovid treatment showing no significant differences.
Oct 14
2025
 Zhou et al., Emerging Microbes & Infections, doi:10.1080/22221751.2025.2552716 SARS-CoV-2 Mpro inhibitor ensitrelvir: asymmetrical cross-resistance with nirmatrelvir and emerging resistance hotspots
In vitro study showing that SARS-CoV-2 develops high-fitness resistance to ensitrelvir through Mpro mutations. Authors found asymmetrical cross-resistance, with ensitrelvir-resistant variants showing minimal cross-resistance to nirmatrelv..
Oct 8
2025
 Jagannathan et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf634 Longitudinal patient-reported outcome trajectories in Long COVID: Findings from the STOP-PASC Clinical Trial
127% higher progression (p=0.14). Secondary analysis of NCT0557666. RCT 155 adults with long COVID showing no benefit from a 15-day course of paxlovid. Patients with worsening symptoms were more likely to be treated with paxlovid, without statistical significance.
Oct 6
2025
 Murad et al., Pulmonary Therapy, doi:10.1007/s41030-025-00316-z A Retrospective Observational Study on COVID-19 Patients Receiving Treatment with Nirmatrelvir/Ritonavir (PAXLOVID)
Retrospective 3,011 outpatients in Bahrain showing lower hospitalization with paxlovid treatment. However, the study has significant methodological limitations that likely substantially overestimate paxlovid's benefit: Contraindicated/sic..
Sep 29
2025
 Ikeuchi et al., BMC Infectious Diseases, doi:10.1186/s12879-025-11651-6 Comparative effectiveness of antiviral treatment on household transmission of SARS-CoV-2: a retrospective cohort study using administrative data
Retrospective 5,398 married couples in Japan showing no significant difference in household transmission rates between molnupiravir, ensitrelvir, and paxlovid. Hospitalized patients receiving antivirals showed a trend toward lower transmi..
Sep 10
2025
 Butler et al., New England Journal of Medicine, doi:10.1056/NEJMoa2502457 (results released 9/10/2025) Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients
18% higher combined mortality/hospitalization (p=0.69), 27% improved recovery (p<0.0001), and 81% improved viral clearance (p=0.006). PANORAMIC/CanTreatCOVID results showing that paxlovid did not reduce hospitalization or death, adjusted OR 1.18, 95% Bayesian credible interval [0.55-2.62] for PANORAMIC and adjusted OR 0.48, 95% Bayesian credible interval [0.08-2.23] for..
Sep 10
2025
 Butler et al., New England Journal of Medicine, doi:10.1056/NEJMoa2502457 (results released 9/10/2025) Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients
52% lower combined mortality/hospitalization (p=0.39) and 42% improved recovery (p<0.0001). Results for the CanTreatCOVID trial. See [Butler] for details.
Sep 10
2025
 Richards et al., New England Journal of Medicine Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients
Moved to [Butler]
Sep 10
2025
 Richards et al., New England Journal of Medicine Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients
Moved to [Butler]
Sep 2
2025
 Horby et al., medRxiv, doi:10.1101/2025.08.29.25334732 Long-term follow-up of treatment comparisons in RECOVERY: a randomised, open-label, platform trial for patients hospitalised with COVID-19
6-month followup of RECOVERY patients. Results are reported within the respective trials for each treatment.
Aug 31
2025
 Sawano et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(25)00073-8 Nirmatrelvir–ritonavir versus placebo–ritonavir in individuals with long COVID in the USA (PAX LC): a double-blind, randomised, placebo-controlled, phase 2, decentralised trial
124% higher long COVID (p=0.56). RCT 100 outpatients with long COVID showing no significant difference with paxlovid. Authors hypothesize that viral reservoirs may have been inaccessible to the drug, or that the dose or duration may have been insufficient to eliminate pe..
Jul 1
2025
 Li et al., BMC Infectious Diseases, doi:10.1186/s12879-025-11195-9 Real-world effectiveness of simnotrelvir-ritonavir versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the omicron wave in China: a retrospective cohort study
Retrospective 585 hospitalized COVID-19 patients in China showing that xiannuoxin provided better clinical improvement than paxlovid. There were no significant differences for progression, mortality, or respiratory support.
Jun 26
2025
 Shen et al., Pharmaceutics, doi:10.3390/pharmaceutics17070832 Carboxylesterase Factors Influencing the Therapeutic Activity of Common Antiviral Medications Used for SARS-CoV-2 Infection
Review of how carboxylesterase (CES) enzymes influence the activity of certain COVID-19 antivirals, focusing on remdesivir, molnupiravir, nirmatrelvir, and favipiravir. Authors highlight that remdesivir requires activation by CES1, while ..
Jun 5
2025
 Negru et al., Biomedicines, doi:10.3390/biomedicines13061387 Comparative Pharmacovigilance Analysis of Approved and Repurposed Antivirals for COVID-19: Insights from EudraVigilance Data
Pharmacovigilance analysis of 64,776 adverse event reports from EudraVigilance comparing safety profiles of COVID-19 antivirals, showing remdesivir associated with more serious adverse events compared to paxlovid. Remdesivir showed consis..
Jun 3
2025
 Deschenes et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiaf294 Functional and structural characterization of treatment-emergent nirmatrelvir resistance mutations at low frequencies in the main protease (Mpro) reveals a unique evolutionary route for SARS-CoV-2 to gain resistance
In vitro and in silico study showing that novel SARS-CoV-2 main protease (Mpro) mutations confer resistance to paxlovid. Authors identified new Mpro clinical variants, including D48D/L58F/P132H and D48D/L67V/K90R/P132H, in patients who re..
May 31
2025
 Dalton et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf567 (date from preprint) Risk of Post-COVID-19 Conditions Among Adolescents and Adults Who Received Nirmatrelvir-Ritonavir for Acute COVID-19: A Retrospective Cohort Study
Retrospective 291,433 paxlovid recipients matched 1:2 to 582,866 untreated COVID-19 outpatients in the USA reporting a modest reduction in long COVID in the primary model for patients 50+. Analysis requiring a positive laboratory test or ..
May 31
2025
 Leitch-Casey et al., American Journal of Respiratory and Critical Care Medicine, doi:10.1164/ajrccm.2025.211.Abstracts.A1193 Toxic as FK - A Case of Paxlovid-Induced Tacrolimus (FK506) Toxicity in a Kidney Transplant Recipient with COVID-19
Case report of a 71-year-old kidney transplant recipient who developed fatal tacrolimus toxicity after being prescribed paxlovid for COVID-19.
May 21
2025
 Schilling et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(25)00482-7 (date from preprint) Antiviral efficacy of oral ensitrelvir versus oral ritonavir-boosted nirmatrelvir in COVID-19
8% faster recovery (p=0.006) and 55% improved viral clearance (p<0.0001). RCT 604 low-risk adults with early COVID-19 symptoms showing significantly improved SARS-CoV-2 viral clearance with both ensitrelvir and paxlovid. Inclusion criteria selected for low-risk patients with high viral loads which may not gener..
May 8
2025
 Tawfiq et al., Health Expectations, doi:10.1111/hex.70273 Long Covid Symptom Clusters, Correlates and Predictors in a Highly Vaccinated Australian Population in 2023
Retrospective 1,205 adults in Australa showing 20% reported long COVID symptoms during an Omicron-predominant period. In multivariable analysis, paxlovid and molnupiravir use showed higher risk of long COVID, without statistical significa..
May 2
2025
 Khoo et al., medRxiv, doi:10.1101/2025.05.01.25326797 A randomised-controlled Phase I de-escalation trial of Molnupiravir and Nirmatrelvir/Ritonavir combination for mild-moderate SARS-CoV-2 infection
1% worse viral clearance (p=0.94). Randomized open-label phase I trial of 24 outpatients with mild-moderate COVID-19 showing safety and tolerability of combined molnupiravir and paxlovid therapy. Supplemental Table 2 shows greater decline of viral load in the control group..
May 1
2025
 Gupta et al., Infectious Disease Reports, doi:10.3390/idr17030043 Incidence of COVID-19 Symptom Rebound After Treatment with Remdesivir
Retrospective 155 patients with mild to moderate COVID-19 showing significantly lower symptom rebound rates with remdesivir compared with paxlovid. Authors provide an analysis of rebound with paxlovid, showing higher rates in prospective ..
Apr 4
2025
 Nishimura et al., Biomedical Research, doi:10.2220/biomedres.46.37 Possible involvement of neuropeptide Y sub-receptor 1 (NPY-Y1) in the anti-viral response of SARS-CoV-2 infection in Syrian hamster
Animal study showing that molnupiravir and remdesivir co-administration reduces SARS-CoV-2 viral load and inflammatory responses in Syrian hamsters, with involvement of neuropeptide Y sub-receptor 1 (NPY-Y1). Authors found that SARS-CoV-2..
Mar 31
2025
 Jia et al., Scientific Reports, doi:10.1038/s41598-025-85677-w Efficacy and safety of azvudine versus nirmatrelvir/ritonavir in cancer patients with COVID-19
PSM retrospective 596 cancer patients with COVID-19 showing that azvudine significantly reduced all-cause mortality and composite disease progression compared to paxlovid.
Mar 17
2025
 Offord et al., JACC: Case Reports, doi:10.1016/j.jaccas.2025.103238 Complete Heart Block Triggered by Nirmatrelvir-Ritonavir and Verapamil
Case report of a 58-year-old woman who developed complete heart block and shock due to a drug-drug interaction between paxlovid and verapamil, exacerbated by acute kidney injury and liver dysfunction. This case highlights potentially leth..
Mar 15
2025
 Zou et al., BMC Pulmonary Medicine, doi:10.1186/s12890-025-03524-0 Risk prediction and early intervention strategies for persistent SARS-CoV-2 infection in patients with non-Hodgkin lymphoma: a retrospective cohort study
5% worse viral clearance (p=0.83). Retrospective 660 patients with non-Hodgkin lymphoma (NHL) and SARS-CoV-2 infection, identifying risk factors for persistent COVID-19. There was no significant difference in persistent SARS-CoV-2 infection with paxlovid, molnupiravir, or ..
Mar 13
2025
 Vukovikj et al., Eurosurveillance, doi:10.2807/1560-7917.ES.2025.30.10.2400252 Impact of SARS-CoV-2 variant mutations on susceptibility to monoclonal antibodies and antiviral drugs: a non-systematic review, April 2022 to October 2024
Review of SARS-CoV-2 variant mutations and their impact on susceptibility to monoclonal antibodies and antivirals. Mutations in the ORF1ab region led to decreased susceptibility to paxlovid, while nsp12 mutations reduced efficacy for remd..
Mar 11
2025
 Al Krad et al., bioRxiv, doi:10.1101/2025.03.09.642200 The protease inhibitor Nirmatrelvir synergizes with inhibitors of GRP78 to suppress SARS-CoV-2 replication
In vitro and animal study showing strong synergistic effects when combining nirmatrelvir with GRP78 inhibitors.
Mar 11
2025
 Pacnejer et al., Journal of Clinical Medicine, doi:10.3390/jcm14061886 Comparative Analysis of Neuropsychiatric Adverse Reactions Associated with Remdesivir and Nirmatrelvir/Ritonavir in COVID-19 Treatment: Insights from EudraVigilance Data
Pharmacovigilance analysis of 8,078 paxlovid 3,934 remdesivir case safety reports from the EudraVigilance database, showing paxlovid associated with significantly higher incidence of neuropsychiatric adverse drug reactions. Paxlovid repor..
Mar 10
2025
 Wang et al., BMC Infectious Diseases, doi:10.1186/s12879-025-10684-1 Development and validation of a nomogram to assess the occurrence of liver dysfunction in patients with COVID-19 pneumonia in the ICU
27% worse results (p<0.0001). Retrospective 286 critically ill COVID-19 ICU patients developing a predictive model for liver dysfunction, showing significantly higher risk with azvudine and paxlovid use.
Mar 3
2025
 He et al., BMC Infectious Diseases, doi:10.1186/s12879-025-10666-3 Prognostic factors in hospitalized patients with COVID-19 pneumonia and effectiveness of prophylactic anticoagulant therapy: a single-center retrospective study
28% higher mortality (p=0.14). Retrospective 2,520 hospitalized COVID-19 pneumonia patients focusing on prophylactic anticoagulation but also reporting results for azvudine and paxlovid.
Feb 26
2025
 Gao et al., Expert Opinion on Drug Safety, doi:10.1080/14740338.2025.2471509 Effects of Nirmatrelvir/ritonavir (paxlovid) on the nervous system: analysis on adverse events released by FDA
Adverse event disproportionality analysis for COVID-19 drugs showing significantly higher risk of neurological adverse events with paxlovid.
Feb 25
2025
 Rao et al., BMC Infectious Diseases, doi:10.1186/s12879-025-10643-w Real-world effectiveness and safety of oral Azvudine versus Paxlovid for COVID-19 in patients with kidney disease: a multicenter, retrospective, cohort study
Retrospective 657 hospitalized COVID-19 patients with kidney disease showing no significant difference in all-cause mortality or disease progression between azvudine and paxlovid. Subgroup analysis showed lower disease progression with az..
Feb 18
2025
 Yang et al., Infectious Medicine, doi:10.1016/j.imj.2025.100169 Clinical outcomes of patients with coronavirus disease 2019 and active tuberculosis co-infection in Beijing China: A retrospective single-center descriptive study
337% higher mortality (p=0.02). Retrospective 102 COVID-19 patients with active tuberculosis co-infection showing a mortality rate of 9.8%, compared with 0.03% for patients with COVID-19 alone. Paxlovid was used for 19 patients due limited availability but resulted in h..
Feb 18
2025
 Wei et al., Emerging Microbes & Infections, doi:10.1080/22221751.2025.2469648 Effectiveness of nirmatrelvir/ritonavir and molnupiravir on post-COVID-19 outcomes among outpatients: a target trial emulation investigation
38% lower mortality (p<0.0001) and 15% lower hospitalization (p<0.0001). Retrospective target trial emulation of outpatients in Hong Kong showing reduced post-acute mortality and hospitalization with paxlovid, but no significant long-term benefit with molnupiravir. Figure 1 shows only 0.08% of patients were ex..
Feb 15
2025
 Jarczak et al., RPS Pharmacy and Pharmacology Reports, doi:10.1093/rpsppr/rqae028 Potential drug interactions with nirmatrelvir/ritonavir in critically ill patients with COVID-19 – a retrospective observational study
Retrospective 500 critically ill COVID-19 patients in Germany showing potential drug-drug interactions with paxlovid in 48% of patients, with higher age and number of comorbidities significantly associated with drug-drug interactions. Aut..
Feb 5
2025
 Mandel et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaf046 Long COVID Incidence Proportion in Adults and Children Between 2020 and 2024: An EHR-Based Study From the RECOVER Initiative
16% higher long COVID (p=0.32). Retrospective 5.4 million patients across three US clinical research networks showing higher use of paxlovid (within 5 days of the index event) in patients with long COVID. Adjusted results for paxlovid’s impact on long COVID risk are not..
Jan 27
2025
 Su et al., iScience, doi:10.1016/j.isci.2025.111907 Real-world effectiveness of azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19 and pre-existing diabetes
Retrospective 954 hospitalized patients with COVID-19 and pre-existing diabetes showing lower mortality with azvudine compared to paxlovid, but no significant difference for composite disease progression.
Jan 27
2025
 Zvornicanin et al., bioRxiv, doi:10.1101/2025.01.24.634813 Molecular Mechanisms of Drug Resistance and Compensation in SARS-CoV-2 Main Protease: The Interplay Between E166 and L50
In vitro study showing that mutations at position E166 in the SARS-CoV-2 main protease (Mpro) confer resistance to nirmatrelvir, the active component of paxlovid, while preserving substrate cleavage. Authors found that E166A and E166V mut..
Dec 31
2024
 Yu et al., Acta Pharmaceutica Sinica B, doi:10.1016/j.apsb.2024.12.032 A retrospective cohort study of the efficacy and safety of oral azvudine versus nirmatrelvir/ritonavir in elderly hospitalized COVID-19 patients aged over 60 years
Retrospective 5,131 elderly hospitalized COVID-19 patients in China showing lower mortality with azvudine compared to paxlovid. There was no significant difference in composite disease progression. Safety analysis showed azvudine had a lo..
Dec 25
2024
 Rowan et al., Pulmonary Therapy, doi:10.1007/s41030-024-00284-w Real-World Effectiveness of Bebtelovimab Versus Nirmatrelvir/Ritonavir in Outpatients with COVID-19
Retrospective 5,827 matched pairs of non-hospitalized COVID-19 patients showing no significant differences between bebtelovimab and paxlovid treatment. Authors do not exclude patients with contraindications for paxlovid.
Dec 12
2024
 Mikhail et al., American Journal of Gastroenterology, doi:10.14309/01.ajg.0001082744.48729.45 Efficacy of Nirmatrelvir/Ritonavir (Paxlovid) for COVID-19 in Vaccinated Patients With Inflammatory Bowel Disease
no change in progression (p=0.97) and 33% lower hospitalization (p=0.14). PSM retrospective 2,773 IBD patients showing no significant difference in hospitalization or the composite outcome of ICU admission, intubation, or mortality with paxlovid treatment. Authors do not specify exclusion of contraindicated pat..
Nov 14
2024
 Lee et al., Pediatric Infectious Disease Journal, doi:10.1097/INF.0000000000004594 Evolving COVID-19 Landscape: Assessing the Effectiveness and Safety Profile of Nirmatrelvir/Ritonavir in Adolescents
813% higher mortality (p=0.06) and 360% higher progression (p=0.1). Retrospective 374 adolescent COVID-19 outpatients showing no significant differences with paxlovid treatment.
Nov 12
2024
 Kim et al., Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043 Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study
FAERS adverse event analysis for remdesivir, bebtelovimab, molnupiravir, and paxlovid. Top 10 signals for serious adverse drug reactions for remdesivir included death and acute kidney injury, for paxlovid: disease recurrence and rebound, ..
Nov 11
2024
 Hammond et al., Clinical Infectious Diseases, doi:10.1093/cid/ciae551 Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial
Additional analysis of [Hammond]. Results are shown with the main paper [Hammond].
Nov 8
2024
 Wang et al., Journal of Global Health, doi:10.7189/jogh.14.05032 Low antiviral uptake of nirmatrelvir/ritonavir and molnupiravir in adult patients with COVID-19 in Taiwan in 2022
Retrospective 96,398 adult COVID-19 patients in Taiwan showing very low use of approved antivirals nirmatrelvir/ritonavir (5.1%) and molnupiravir (1.9%) in 2022, especially in moderate-to-high risk groups eligible for treatment per WHO gu..
Nov 5
2024
 Yu et al., Blood, doi:10.1182/blood-2024-207488 Nirmatrelvir/Ritonavir Reduces Infection Duration in Hospitalized Hematological Malignancies Patients with Mild-to-Moderate COVID-19: A Retrospective Study
9% lower mortality (p=0.92) and 34% improved recovery (p=0.04). Retrospective 130 hematological malignancy patients with mild-to-moderate COVID-19 in China showing no significant difference in 90-day mortality, but shorter infection duration with paxlovid treatment within 5 days.
Oct 28
2024
 Vogel et al., Research Square, doi:10.21203/rs.3.rs-5314583/v1 A randomized trial of at-home COVID-19 tests, telemedicine, and rapid prescription delivery for immunocompromised individuals
RCT 671 immunocompromised or aged 65+ participants in the US showing significantly reduced ICU admissions and cost of COVID care with access to at-home COVID tests, telemedicine, and rapid paxlovid delivery. There was no significant diffe..
Oct 19
2024
 Thomas et al., bioRxiv, doi:10.1101/2024.10.18.619137 Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator
In vitro study showing that paxlovid use may promote the emergence of SARS-CoV-2 variants that can weaken host immunity and potentially contribute to long COVID. Authors show that SARS-CoV-2 main protease (Mpro) mutations that confer resi..
Oct 17
2024
 Stoiber et al., International Journal of Clinical Pharmacy, doi:10.1007/s11096-024-01852-5 (date from preprint) Frequency, type and severity of drug-related problems and pharmacist interventions in Paxlovid® prescribing: a descriptive analysis
Retrospective 140 hospitalized COVID-19 patients in Austria showing that pharmacist review identified a high rate of drug-related problems (DRPs) with paxlovid prescribing, including drug-drug interactions (DDIs) and inappropriate dosing ..
Oct 8
2024
 Zhang et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaf548 (results released 10/8/2024) Retreatment With Nirmatrelvir/Ritonavir Following Return of COVID-19 Symptoms and SARS-CoV-2 Positivity
8% improved recovery (p=0.52) and 18% improved viral clearance (p=0.0004). RCT 436 patients with post-paxlovid rebound showing improved viral load at day 5 but no significant difference in recovery time or viral clearance with repeated paxlovid treatment vs. placebo/ritonavir.
Oct 3
2024
 Quinlan et al., MMWR. Morbidity and Mortality Weekly Report, doi:10.15585/mmwr.mm7339a3 Differences in COVID-19 Outpatient Antiviral Treatment Among Adults Aged ≥65 Years by Age Group — National Patient-Centered Clinical Research Network, United States, April 2022–September 2023
Retrospective 393,390 COVID-19 patients aged ≥65 years showing underutilization of antiviral treatment, with lower use for older patients at higher risk for severe outcomes.
Sep 27
2024
 Zabek, M., Electronic Thesis and Dissertation Repository, 10427 The Transfer of Molnupiravir and Nirmatrelvir Across the Human Placenta and Prediction of Drug Safety in Pregnancy
Ex vivo study showing placental transfer of molnupiravir (NHC) and nirmatrelvir in human placentas. Author used a placental perfusion model to assess drug transfer across the human placental barrier. Both compounds readily crossed the pla..
Sep 25
2024
 Tamura et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2024.35431 Emerging SARS-CoV-2 Resistance After Antiviral Treatment
Prospective study of 156 outpatients showing emergent nirmatrelvir resistance mutations with nirmatrelvir treatment, especially in immunosuppressed individuals. Results support the use of combination antiviral therapy and host-directed tr..
Sep 25
2024
 Bennett et al., PLOS ONE, doi:10.1371/journal.pone.0308205 A SONAR report on Nirmatrelvir/ritonavir-associated rebound COVID-19: Using new databases for evaluating new diseases
Retrospective case series identifying 35 cases of presumed or documented paxlovid rebound COVID-19 infection from pre-print articles, social media posts, and news reports. Authors highlight a delay of 2-3 months for reports to appear in p..
Sep 18
2024
 Nooruzzaman et al., Nature Communications, doi:10.1038/s41467-024-51924-3 Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections
Analysis of 15 immunocompromised patients with persistent SARS-CoV-2 infection showing emergence of putative antiviral resistance mutations in nsp5 and nsp12 following treatment with remdesivir and nirmatrelvir-ritonavir. An infectious SA..
Sep 7
2024
 Mozaffari et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2024.08.004 Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients
Retrospective 788,238 hospitalized COVID-19 patients in the US, showing a very high prevalence of drug-drug interactions with paxlovid, with higher prevalence for older patients, patients with more comorbidities, and patients at high-risk..
Aug 31
2024
 Deng et al., Translational Cancer Research, doi:10.21037/tcr-24-70 Effectiveness of Paxlovid in the treatment of the SARS-CoV-2 Omicron variant infection in children with hematologic malignancies: a retrospective cohort study
Retrospective 42 children with hematologic malignancies (HMs) and SARS-CoV-2 omicron infection showing no significant difference in clinical outcomes or viral clearance with paxlovid after propensity score matching.
Aug 20
2024
 Yen et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09654-w Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan
31% lower mortality (p=0.25). Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing lower mortality with paxlovid, without statistical significance. Authors report that all infected patients were hospitalized at the time of ..
Aug 14
2024
 Lai et al., Age and Ageing, doi:10.1093/ageing/afae180 Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study
20% lower mortality (p=0.01). Target trial emulation study of 13,642 (molnupiravir) and 9,553 (paxlovid) elderly hospitalized patients in Hong Kong showing lower mortality with treatment.
Aug 12
2024
 Nair et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiae385 Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro
In vitro study showing the persistence of an infectious form of SARS-CoV-2 after treatment with 3CLpro inhibitors nirmatrelvir and ensitrelvir, which may explain the rebound often seen with paxlovid. 3CLpro is crucial for processing viral..
Aug 5
2024
 Low et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09679-1 Nirmatrelvir/ritonavir treatment and the risk of post-COVID condition over 180 days in Malaysia
30% higher long COVID (p=0.34). Retrospective 2,524 adult COVID-19 outpatients in Malaysia showing no significant difference in post-COVID condition (PCC) at 3 months and 6 months with paxlovid treatment.
Aug 1
2024
 Zong et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09482-y Paxlovid reduces the 28-day mortality of patients with COVID-19: a retrospective cohort study
Retrospective 1,018 hospitalized COVID-19 patients in China, showing lower 28-day mortality with paxlovid. This study contains significant confounding issues that could potentially account for the entire benefit seen: The control group in..
Jul 18
2024
 Hammond et al., New England Journal of Medicine, doi:10.1056/NEJMoa2309002 Oral Nirmatrelvir–Ritonavir as Postexposure Prophylaxis for Covid-19
Delayed publication of the EPIC-PEP RCT showing no significant benefit with paxlovid for post-exposure prophylaxis. Results were available in 2023 on clinicaltrials.gov [Pfizer].
Jul 15
2024
 Choi et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0 Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study
34% lower mortality (p=0.006), 37% lower ICU admission (p=0.26), and 45% lower need for oxygen therapy (p=0.03). Target trial emulation study of 18,196 hospitalized COVID-19 patients in Hong Kong showing significantly higher ICU admission and AKI with remdesivir + paxlovid compared with paxlovid alone, and lower mortality and ventilatory support wit..
Jul 6
2024
 Zhao et al., Quantitative Biology, doi:10.1002/qub2.60 Assessing the inhibition efficacy of clinical drugs against the main proteases of SARS‐CoV‐2 variants and other coronaviruses
In vitro study showing that leritrelvir and GC376 remained effective against some nirmatrelvir- and ensitrelvir-resistant Mpro mutants. Leritrelvir showed better broad-spectrum activity against other pathogenic coronaviruses compared to e..
Jul 5
2024
 Brewitz et al., Journal of Medicinal Chemistry, doi:10.1021/acs.jmedchem.4c01342 Fixing the Achilles Heel of Pfizer’s Paxlovid for COVID-19 Treatment
Perspective article discussing the development of ibuzatrelvir (PF-07817883) as a SARS-CoV-2 main protease (Mpro) inhibitor which addresses the metabolic instability of nirmatrelvir and does not require co-administration with ritonavir, t..
Jun 27
2024
 Kamo et al., In Vivo, doi:10.21873/invivo.13637 Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure
Retrospective 176,197 adverse event reports in Japan showing paxlovid and remdesivir associated with increased risk of acute kidney injury (AKI) in COVID-19 patients.
Jun 24
2024
 Lv et al., Journal of Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, doi:10.1631/jzus.B2300538 Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study
495% higher mortality (p<0.0001). Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January ..
Jun 24
2024
 Lopez et al., Current Clinical Microbiology Reports, doi:10.1007/s40588-024-00229-6 SARS-CoV-2 Resistance to Small Molecule Inhibitors
Review of resistance mutations in SARS-CoV-2 3CLpro and nsp12 that could reduce efficacy of antiviral therapies including nirmatrelvir, ensitrelvir, remdesivir, and favipiravir. Authors identify 39 single mutations across 17 critical resi..
Jun 7
2024
 Geng et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2024.2007 Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection
RCT 155 adults with long COVID (PASC) showing no significant benefit with paxlovid compared to ritonavir.
Jun 3
2024
 Verma et al., bioRxiv, doi:10.1101/2024.06.02.596989 Persistent Neurological Deficits in Mouse PASC Reveal Antiviral Drug Limitations
Mouse study showing persistent neurological deficits after SARS-CoV-2 infection, and failure of nirmatrelvir and molnupiravir to prevent neurological damage. Authors found decreased tyrosine hydroxylase expression in the olfactory bulb an..
May 24
2024
 Horby et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(25)00093-3 (date from preprint) Molnupiravir or nirmatrelvir-ritonavir versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
1% higher mortality (p=1), 35% lower hospital discharge (p=0.33), and 19% improved viral clearance (p<0.0001). RECOVERY RCT showing no significant differences in mortality, ventilation, or discharge with either molnupiravir (923 patients) or paxlovid (137 patients). Viral load was improved with treatment but did not translate into clinical benefit..
Sep 17
2024
 Lieber et al., Journal of Virology, doi:10.1128/jvi.00905-24 (date from preprint) Efficacy of late-onset antiviral treatment in immunocompromised hosts with persistent SARS-CoV-2 infection
Mouse study showing that late-onset treatment with paxlovid, molnupiravir, or 4'-FlU significantly reduced persistent SARS-CoV-2 infection in immunocompromised mice, with 4'-FlU being most effective. Authors used a CD4+ and CD8+ T cell-de..
Apr 30
2024
 Liu et al., Infections in the immunosuppressed and immunocompromised host, doi:10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A2917 Effectiveness of Azvudine and Nirmatrelvir-ritonavir in Kidney Transplant Recipients With COVID-19: A Retrospective Cohort Study
272% higher progression (p=0.05). Retrospective 148 hospitalized kidney transplant patients with COVID-19 in China showing lower risk of disease progression with azvudine treatment compared, and higher risk with paxlovid treatment.
Apr 28
2024
 de Oliveira Só et al., Preprints, doi:10.20944/preprints202404.1825.v1 In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease
In silico study showing that ivermectin and nirmatrelvir interact with the SARS-CoV-2 main protease (Mpro). Authors used molecular docking and 100ns molecular dynamics simulations to investigate the binding interactions. Nirmatrelvir form..
Apr 5
2024
 Chen et al., Immunity, Inflammation and Disease, doi:10.1002/iid3.1232 Nirmatrelvir and ritonavir combination against COVID‐19 caused by omicron BA.2.2 in the elderly: A single‐center large observational study
PSM retrospective 648 elderly COVID-19 patients showing no significant difference in time to viral clearance with paxlovid. However, in subgroup analysis of patients treated within 10 days of symptom onset, treatment was associated with f..
Apr 2
2024
 Lewandowski et al., bioRxiv, doi:10.1101/2024.04.01.587566 Distal Protein-Protein Interactions Contribute to SARS-CoV-2 Main Protease Substrate Binding and Nirmatrelvir Resistance
In vitro and crystallographic study reveals that the L50F mutation in SARS-CoV-2 main protease (Mpro) can restore the reduced enzymatic activity caused by nirmatrelvir resistance mutations E166A/L167F through enhanced protein-protein inte..
Mar 31
2024
 Choe et al., Pharmacoepidemiology and Risk Management, doi:10.56142/perm.24.0006 Safety Monitoring of Oral Antiviral COVID-19 Treatment Using Korea Adverse Event Reporting System (KAERS) Database
Safety analysis of paxlovid and molnupiravir. Disproportionality analysis found significant signals for paxlovid with sensory abnormalities, interactions, fecal abnormalities, and signals not on the label including olfactory nerve disorde..
Mar 29
2024
 Yang et al., Infection and Drug Resistance, doi:10.2147/IDR.S443574 Reduced Viral Shedding Time in High-Risk COVID-19 Patients Infected by Omicron and Treated with Paxlovid: A Real-World Study from China
Retrospective 3,159 high risk COVID-19 patients in China showing no significant difference for viral clearance with multivariable Cox regression, but significantly faster viral clearance with logistic regression. Cox results account for t..
Mar 29
2024
 Malden et al., Scientific Reports, doi:10.1038/s41598-024-57633-7 Predictors of nirmatrelvir–ritonavir receipt among COVID-19 patients in a large US health system
Retrospective 319,900 treatment-eligible COVID-19 patients showing relatively low use of paxlovid and significant socioeconomic disparities. Treated patients were more likely to be from affluent neighborhoods, be up to date on vaccination..
Mar 13
2024
 Yang et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2024.1765 COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment
RCT showing high rates of viral and symptom rebound with both paxlovid and deuremidevir (VV116). There are multiple potential reasons, with one being the highly specific targets within viral replication (Mpro and RdRp respectively). Paxlo..
Mar 4
2024
 Liu et al., Medical Review, doi:10.1515/mr-2023-0068 Clinical characteristics and pharmacokinetics of PAXLOVID in COVID-19 patients with hematological tumor
Retrospective 12 hospitalized COVID-19 patients with hematological malignancies showing one death and two cases of liver injury with paxlovid treatment. The study focused on pharmacokinetics, finding nirmatrelvir concentrations approximat..
Mar 2
2024
 Schreiber et al., Antiviral Research, doi:10.1016/j.antiviral.2024.105840 The host-targeted antiviral drug Zapnometinib exhibits a high barrier to the development of SARS-CoV-2 resistance
In vitro study showing that molnupiravir and paxlovid induced resistant variants in SARS-CoV-2 during serial passaging, while the host-directed antiviral zapnometinib did not. Authors found that molnupiravir did not lead to abrogated vira..
Feb 29
2024
 Bouzidi et al., Antiviral Research, doi:10.1016/j.antiviral.2024.105814 Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains
In vitro and animal study showing that SARS-CoV-2 can develop resistance to nirmatrelvir and ensitrelvir. Authors generated resistant viral strains through repeated passaging with both drugs. For nirmatrelvir, they identified three differ..
Feb 21
2024
 Henderson et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkae042 COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina
84% lower hospitalization (p=0.002). EHR retrospective 44,671 patients with 4,948 receiving paxlovid, showing lower hospitalization with treatment.
Feb 9
2024
 Chen et al., Scientific Reports, doi:10.1038/s41598-024-53862-y Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study
Retrospective 157 hospitalized mild-to-moderate COVID-19 patients showing no significant differences between azvudine, molnupiravir, and paxlovid for time to viral clearance and length of hospitalization.
Feb 9
2024
 Wang et al., eClinicalMedicine, doi:10.1016/j.eclinm.2024.102468 Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study
13% lower mortality (p=0.67) and 22% higher progression (p=0.49). Retrospective 249 elderly patients with severe COVID-19, 128 treated with azvudine, 66 treated with paxlovid, and 55 receiving neither treatment, showing no significant differences for Ct value changes, progression, or survival for either..
Feb 9
2024
 Cheng et al., Kidney International Reports, doi:10.1016/j.ekir.2024.02.009 Effectiveness of molnupiravir and nirmatrelvir–ritonavir in CKD patients with COVID-19
22% lower mortality (p=0.05), 1% higher need for oxygen therapy (p=0.96), and 14% lower ICU admission (p=0.5). Retrospective emulated target trial of hospitalized COVID-19 patients with chronic kidney disease in Hong Kong showing lower mortality with molnupiravir and paxlovid treatment. No significant reduction was found in ICU admission or ventil..
Jan 31
2024
 Zhu et al., The Journal of Infection in Developing Countries, doi:10.3855/jidc.18138 Clinical characteristics and risk factors of non-mild outcomes in patients with Omicron variant COVID-19 in Shanghai, China
79% worse viral clearance (p<0.0001). Retrospective 311 COVID-19 patients in China showing significantly slower viral clearance with paxlovid in multivariable analysis.
Jan 31
2024
 Peng et al., Technology in Cancer Research & Treatment, doi:10.1177/15330338241248573 Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer
79% higher mortality (p=0.42). Retrospective 166 hospitalized NSCLC patients with COVID-19 showing no significant difference in mortality with paxlovid or azvudine in univariate analysis.
Jan 26
2024
 Wilcock et al., JAMA Health Forum, doi:10.1001/jamahealthforum.2023.5044 Clinical Risk and Outpatient Therapy Utilization for COVID-19 in the Medicare Population
Analysis of Medicare beneficiaries in 2022 showing that outpatient COVID-19 treatments like antivirals and monoclonal antibodies were disproportionately used by patients at lower risk of severe infection and outcomes. Retrospective studie..
Jan 24
2024
 Guermazi et al., Research Square, doi:10.21203/rs.3.rs-3876022/v1 Oral antivirals for COVID-19 among patients with cancer
Retrospective 67 cancer outpatients treated with nirmatrelvir/ritonavir or molnupiravir, compared to 56 untreated concurrent controls, reporting lower mortality with treatment. However, Figure 3 shows the opposite results for invasive mec..
Jan 24
2024
 Lee et al., npj Viruses, doi:10.1038/s44298-023-00013-1 The anti-COVID-19 drug Paxlovid crosses biological barriers of the placenta and brain in rats
Animal study showing that paxlovid crosses biological barriers of the blood-placenta and blood-brain in rats. Authors developed a multisite microdialysis coupled with UHPLC-MS/MS to monitor nirmatrelvir levels in maternal blood, conceptus..
Jan 22
2024
 Preiss et al., PLOS Medicine, doi:10.1371/journal.pmed.1004711 (date from preprint) Effect of Paxlovid treatment during acute COVID-19 on Long COVID onset: An EHR-based target trial emulation from the N3C and RECOVER consortia
1% lower long COVID (p=0.59). Retrospective 445,378 high-risk outpatients showing no significant difference in post-acute sequelae of COVID-19 (PASC) incidence with paxlovid treatment. Subgroup analysis showed benefits for cognitive and fatigue symptoms. The study use..
Jan 15
2024
 Jung et al., Toxics, doi:10.3390/toxics12010073 Ritonavir Has Reproductive Toxicity Depending on Disrupting PI3K/PDK1/AKT Signaling Pathway
In vitro study on boar spermatozoa showing that the HIV drug ritonavir (part of paxlovid and xiannuoxin) causes reproductive toxicity by disrupting the PI3K/PDK1/AKT signaling pathway. Ritonavir suppressed sperm functions including motili..
Jan 8
2024
 Choi et al., SSRN, doi:10.2139/ssrn.4683854 Comparative Efficacy of Combination Treatment with Nirmatrelvir-Ritonavir and Remdesivir Versus Remdesivir Monotherapy in Hospitalised COVID-19 Patients: A Target Trial Emulation Study
37% lower mortality (p=0.004), 40% higher ICU admission (p=0.78), and 20% lower need for oxygen therapy (p=0.66). Retrospective 1,843 hospitalized COVID-19 patients in Hong Kong showing lower mortality with paxlovid. All patients received remdesivir. No significant difference was found for ICU admission or ventilatory support.
Jan 4
2024
 Durstenfeld et al., Journal of Medical Virology, doi:10.1002/jmv.29333 Association of nirmatrelvir for acute SARS‐CoV‐2 infection with subsequent Long COVID symptoms in an observational cohort study
14% higher long COVID (p=0.4). Retrospective 4,684 COVID+ patients mostly in the USA, 988 treated with paxlovid, showing higher risk of long COVID with treatment, without statistical significance.
Dec 31
2023
 Bischof, E., Aging and disease, doi:10.14336/AD.2023.0318 Mitigating COVID-19 Mortality and Morbidity in China's Aging Population: A Focus on Available Medications and Future Developments
Review focusing on 3CL protease inhibitors. First generation inhibitors like paxlovid and simnotrelvir require boosting with ritonavir, which can cause drug-drug interactions and other issues. Second generation inhibitors like ensitrelvir..
Dec 22
2023
 Xu et al., Medicine, doi:10.1097/MD.0000000000036714 Impact of Paxlovid on in-hospital outcomes and post-COVID-19 condition in adult patients infected with SARS-CoV-2 Omicron variant: A non-randomized controlled clinical trial
12% shorter hospitalization (p=0.09), 35% faster recovery (p<0.0001), 58% faster viral clearance (p<0.0001), and 47% lower long COVID (p=0.04). Prospective study of 320 COVID-19 patients infected with the SARS-CoV-2 Omicron variant in China, showing improved viral clearance and symptom resolution with 5 days of paxlovid treatment. Authors perform multivariable analysis for post-c..
Dec 19
2023
 Lombardo et al., Microorganisms, doi:10.3390/microorganisms12010002 Assessing Genomic Mutations in SARS-CoV-2: Potential Resistance to Antiviral Drugs in Viral Populations from Untreated COVID-19 Patients
Analysis of naturally occurring SARS-CoV-2 mutations in genomic regions targeted by remdesivir, molnupiravir, and paxlovid in 4,155 antiviral-naive COVID-19 patients. Authors identified 84 amino-acid substitutions in Nsp12 (RdRp; target o..
Nov 30
2023
 Xu et al., Clinical Interventions in Aging, doi:10.2147/cia.s431271 Factors Affecting Mortality in Elderly Hypertensive Hospitalized Patients with COVID-19: A Retrospective Study
232% higher mortality (p=0.006). Retrospective 748 elderly hospitalized COVID-19 patients in China showing increased risk of death with paxlovid/molnupiravir. Multivariate analysis showed that paxlovid/molnupiravir was independently associated with higher in-hospital mor..
Nov 30
2023
 Uraki et al., iScience, doi:10.1016/j.isci.2023.108147 Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate
In vitro and animal study showing that the SARS-CoV-2 omicron subvariant XBB.1.9.1 has similar antigenicity, antiviral susceptibility, and replicative ability compared to XBB.1.5. Casirivimab, imdevimab, tixagevimab, cilgavimab, sotrovima..
Oct 31
2023
 Ioannou et al., Annals of Internal Medicine, doi:10.7326/M23-1394 Effectiveness of Nirmatrelvir–Ritonavir Against the Development of Post–COVID-19 Conditions Among U.S. Veterans
1% lower long COVID (p=0.75). Retrospective 9,593 veterans in the USA treated with paxlovid, matched to 9,593 untreated controls, showing no significant difference in post-COVID conditions across 31 different conditions. There was lower risk for the combination of 2 s..
Oct 31
2023
 Low et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2023.08.003 Real-world nirmatrelvir-ritonavir outpatient treatment in reducing hospitalization for high-risk patients with COVID-19 during Omicron BA.4, BA.5 and XBB subvariants dominance in Malaysia: A retrospective cohort study
36% lower hospitalization (p=0.03). Retrospective 31,483 high-risk COVID-19 outpatients in Malaysia showing lower risk of hospitalization with paxlovid.
Oct 31
2023
 Li et al., Biosafety and Health, doi:10.1016/j.bsheal.2023.08.004 Viral rebound and safety of nirmatrelvir/ritonavir for lung-transplant recipients infected with SARS-CoV-2
Prospective study of 4 lung transplant recipients showing viral rebound in all patients after initial paxlovid treatment. All four patients received paxlovid within 2 days of SARS-CoV-2 infection, with viral loads initially decreasing but..
Oct 23
2023
 Fung et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2023.5099 Nirmatrelvir and Molnupiravir and Post–COVID-19 Condition in Older Patients
7% lower long COVID (p<0.0001). Retrospective 51,658 paxlovid patients in the USA showing a small reduction in long COVID with treatment. Confounding is likely significant as below, and may eliminate the benefit. Results specific to the COVID-19 code should be closer to..
Oct 21
2023
 Liu et al., Heliyon, doi:10.1016/j.heliyon.2023.e21387 Clinical characteristics, outcomes, and risk factors of SARS-CoV-2 breakthrough infections among 572 fully vaccinated (BBIBP-CorV) hospitalized patients
94% higher progression (p=0.007). Retrospective 572 fully vaccinated hospitalized patients in China, showing higher risk with paxlovid use. The composite outcome included intubation, non-invasive respiratory support, ICU admission, and all-cause death. Details for analysi..
Oct 18
2023
 Lu et al., Infection and Drug Resistance, doi:10.2147/IDR.S430101 Clinical Characteristics of Severe COVID-19 Patients During Omicron Epidemic and a Nomogram Model Integrating Cell-Free DNA for Predicting Mortality: A Retrospective Analysis
6% higher mortality (p=0.84). Retrospective 282 severe COVID-19 patients, showing no significant difference in mortality with paxlovid in unadjusted results.
Oct 18
2023
 Guo et al., BMC Infectious Diseases, doi:10.1186/s12879-023-08620-2 In-hospital adverse outcomes and risk factors among chronic kidney disease patients infected with the omicron variant of SARS-CoV-2: a single-center retrospective study
10% slower viral clearance (p=0.04). Retrospective 1,978 hospitalized patients in China, showing slower viral clearance with Paxlovid. Authors note improved results in the subgroup of non-severe patients with CKD.
Oct 13
2023
 Wei et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1274294 Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching
no change in mortality (p=1), 38% higher ventilation (p=0.04), 122% higher ICU admission (p=0.05), and 28% higher progression (p=0.07). PSM retrospective 725 hospitalized COVID-19 patients in China compared the effectiveness and safety of the oral antivirals azvudine and paxlovid. There was no significant difference in the risk of disease progression between groups, but a..
Oct 12
2023
 Zhou et al., Frontiers in Microbiology, doi:10.3389/fmicb.2023.1280026 Secondary pulmonary infection and co-infection in elderly COVID-19 patients during the pandemics in a tertiary general hospital in Beijing, China
39% higher mortality (p=0.04). Retrospective 322 hospitalized patients ≥65 in China, showing higher mortality with paxlovid use. Details for analysis of confounding are not provided and authors note use may have been higher for more severe patients. The results for pax..
Oct 5
2023
 Lin et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2023.10.007 Clinical outcomes of nirmatrelvir-ritonavir use in pregnant women during the Omicron wave of the coronavirus disease 2019 pandemic
633% higher need for oxygen therapy (p=0.05) and 35% faster recovery (p=0.04). Retrospective 85 pregnant patients in Taiwan, 30 treated with paxlovid, showing higher oxygen requirements, not quite reaching statistical significance (p=0.05), and faster recovery. Patients taking paxlovid for less than three consecutiv..
Oct 2
2023
 Dormuth et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2023.36678 Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications
29% lower combined mortality/hospitalization (p=0.02) and 8% lower progression (p=0.37). Retrospective 3,433 high-risk patients and matched controls in Canada showing lower mortality with paxlovid use. Patients were divided into four groups based on risk, with improved results as risk increased. Authors did not exclude all..
Sep 28
2023
 Pochtovyi et al., Vaccines, doi:10.3390/vaccines11101533 In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1
In vitro study showing sharply reduced neutralization of SARS-CoV-2 variants XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1 with monoclonal antibodies cilgavimab, tixagevimab, imdevimab, etsevimab, casirivim..
Sep 28
2023
 Li et al., Frontiers in Medicine, doi:10.3389/fmed.2023.1238713 Differences in the severity and mortality risk factors for patients hospitalized for COVID-19 pneumonia between the early wave and the very late stage of the pandemic
18% lower mortality (p=0.61). Retrospective 223 hospitalized patients in China, showing no significant difference in mortality with paxlovid in unadjusted results.
Aug 31
2023
 Dian et al., Journal of Infection, doi:10.1016/j.jinf.2023.05.012 Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities
175% higher mortality (p=0.11), 200% higher ventilation (p=0.28), and 94% higher progression (p=0.03). Retrospective 2,118 hospitalized COVID-19 patients in China, showing improved results with azvudine vs. paxlovid.
Aug 20
2023
 Moghadasi et al., npj Antimicrobials and Resistance, doi:10.1038/s44259-023-00009-0 Rapid resistance profiling of SARS-CoV-2 protease inhibitors
In vitro study of SARS-CoV-2 main protease (Mpro) variants showing distinct resistance profiles for the Mpro inhibitors nirmatrelvir, ensitrelvir, and FB2001. Results show significant resistance for multiple variants for nirmatrelvir and ..
Aug 16
2023
 Yu et al., Phytomedicine, doi:10.1016/j.phymed.2023.155025 Efficacy and safety of Huashi Baidu granule plus Nirmatrelvir-Ritonavir combination therapy in patients with high-risk factors infected with Omicron (B.1.1.529): A multi-arm single-center, open-label, randomized controlled trial
2% higher severe cases (p=1), 6% lower hospital discharge (p=0.78), and 12% improved viral clearance (p=0.33). RCT 312 hospitalized COVID-19 patients in China, showing no significant difference between paxlovid and Huashi Baidu treatment. Combination therapy showed improved results to either treatment alone.
Aug 7
2023
 Gbinigie et al., BMJ Open, doi:10.1136/bmjopen-2022-069176 Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease
PANORAMIC protocol paper, published over 9 months after publication of the molnupiravir arm [Butler].
Jul 23
2023
 Shao et al., Microorganisms, doi:10.3390/microorganisms11071859 Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China
29% lower mortality (p=0.16) and 28% worse results (p<0.0001). Retrospective 1,082 severely and critically ill COVID-19 patients in China showing lower 60 day mortality with azvudine. Mortality was also lower with paxlovid, but without statistical significance, and health related quality of life was..
Jul 10
2023
 Kim et al., Journal of Korean Medical Science, doi:10.3346/jkms.2023.38.e211 Effectiveness of Paxlovid, an Oral Antiviral Drug, Against the Omicron BA.5 Variant in Korea: Severe Progression and Death Between July and November 2022
31% lower mortality (p<0.0001) and 43% lower severe cases (p<0.0001). Retrospective 1,936,925 COVID-19 patients in South Korea, showing lower mortality with paxlovid.
Jun 27
2023
 Edelstein et al., medRxiv, doi:10.1101/2023.06.23.23288598 SARS-CoV-2 virologic rebound with nirmatrelvir-ritonavir therapy
761% worse viral clearance (p=0.04). Prospective study of 127 COVID-19 patients in the USA showing higher risk of replication-competent virologic rebound with paxlovid treatment. Authors note that rebound substantially increases the duration of shedding of replication-compet..
Jun 26
2023
 Fu et al., Authorea, Inc., doi:10.22541/au.168777909.90198442/v1 Comparison of the Different Medications for COVID-19 in Kidney Transplant Recipients
280% higher ventilation (p=0.32), 659% higher ICU admission (p=0.04), and 207% higher progression (p=0.005). Retrospective 140 kidney transplant patients, showing higher risk of AKI with paxlovid compared with azvudine. There were more severe cases in the paxlovid group at baseline.
Jun 22
2023
 Yang et al., Elsevier BV, doi:10.2139/ssrn.4488145 Clinical Prognosis and Risk Factors of Death for Covid-19 Patients Complicated with Coronary Heart Disease/Diabetes/Hypertension-A Retrospective, Real-World Study
2% lower mortality (p=0.04). Retrospective 1,281 COVID-19 patients with comorbidities in China, showing 2% lower mortality with paxlovid.
Jun 17
2023
 Wee et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2023.06.016 Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalisations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5 and XBB transmission
14% lower severe cases (p=0.63) and 35% lower hospitalization (p=0.002). Retrospective 3,959 paxlovid patients and 139,379 untreated controls, showing lower hospitalization with treatment. Contraindicted patients were excluded.
Jun 16
2023
 Park et al., Research Square, doi:10.21203/rs.3.rs-3003449/v1 The association of mortality with vaccination and underlying disease among COVID-19 patients in long term care hospitals at Daegu and Gyeonsangbuk-do in Korea
5% lower mortality (p=0.86). Retrospective 2,507 COVID-19 patients at 18 long term care hospitals with COVID-19 outbreaks in Korea, showing no significant difference in mortality with paxlovid treatment. Note that this study is less affected by the typical confoundin..
May 14
2023
 Shao et al., medRxiv, doi:10.1101/2023.05.10.23289325 Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China
29% lower mortality (p=0.16) and 28% worse recovery (p<0.0001). Retrospective 1,082 hospitalized COVID-19 patients in China, showing lower mortality and worse quality of life with paxlovid.
May 10
2023
 Torti et al., Elsevier BV, doi:10.2139/ssrn.4444431 Real-Life Comparison of Mortality in Non-Hospitalised Patients with SARS-CoV-2 Infection at Risk for Clinical Progression Treated with Molnupiravir or Nirmatrevir Plus Ritonavir During the Omicron Era in Italy: A Nationwide, Observational Study
32% lower mortality (p=0.0001). Prospective study of 17,977 outpatients treated with molnupiravir and 11,576 treated with paxlovid, showing significant mortality with both treatments, and lower mortality with paxlovid.
Apr 30
2023
 Wan et al., Annals of Internal Medicine, doi:10.7326/M22-3057 Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Hospitalized Patients With COVID-19
23% lower mortality (p=0.001), 3% higher ventilation (p=0.89), and 8% higher ICU admission (p=0.82). Target trial emulation retrospective with 7,119 patients in Hong Kong, showing lower mortality with paxlovid, but no significant difference for ventilation and ICU admission. See also [acpjournals.org], [acpjournals.org].
Apr 25
2023
 Li et al., Frontiers in Pediatrics, doi:10.3389/fped.2023.1160929 Clinical efficacy analysis of paxlovid in children with hematological diseases infected with the omicron SARS-CoV-2 new variant
51% worse recovery (p=0.008) and 58% faster viral clearance (p=0.03). Retrospective 20 pediatric hematological disease patients in China, showing faster viral clearance with paxlovid, but slower resolution of fever.
Apr 6
2023
 Patel et al., medRxiv, doi:10.1101/2023.04.05.23288196 Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir
20% lower long COVID (p=0.01). TriNetX retrospective 1,004 paxlovid patients and matched controls, showing lower risk of PASC with treatment.
Mar 31
2023
 Moghadasi et al., Science Advances, doi:10.1126/sciadv.ade8778 Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors
Analysis of naturally occurring SARS-CoV-2 main protease variants for resistance to nirmatrelvir and ensitrelvir. Authors identified multiple single amino acid mutations that confer significant resistance to these drugs. Phylogenetic anal..
Mar 23
2023
 Igho-Osagie et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2023.03.012 Prevalence of Potential Drug-Drug Interactions with Ritonavir-Containing COVID-19 therapy in the United States: An Analysis of the National Health and Nutrition Examination Survey
Analysis of 15,685 adults in the USA estimating that 29.3% of the population risk a major or contraindicated drug interaction with paxlovid, which may increase significantly for patients over 60 or with several comorbidities that also inc..
Mar 22
2023
 Yan et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1147980 Nirmatrelvir/ritonavir for patients with SARS-CoV-2 infection and impaired kidney function during the Omicron surge
31% lower mortality (p=0.5), 44% lower progression (p=0.04), 14% lower ICU admission (p=0.61), and 9% shorter hospitalization (p=0.03). Retrospective 195 patients with impaired kidney function in China, showing lower combined mortality/ICU/cardiovascular events, and improved viral clearance with paxlovid.
Mar 15
2023
 Lewnard et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(23)00118-4 Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system
40% higher mortality (p=0.34), 84% lower combined mortality/ICU admission (p=0.03), and 54% lower combined mortality/hospitalization (p=0.03). Retrospective 7,274 outpatients in the USA treated with paxlovid and matched controls, showing lower combined hospitalization/death with treatment. With a small percentage of eligible patients receiving treatment, confounding by indicatio..
Mar 13
2023
 Kim et al., Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2221857120 Computational prediction of interactions between Paxlovid and prescription drugs
In silico analysis of drug-drug interactions for paxlovid. From 2,248 prescription drugs, 1,628 were predicted to have 2,445 interactions with nirmatrelvir and/or ritonavir (673 for nirmatrelvir and 1,403 ritonavir). For 873 drugs, author..
Feb 22
2023
 Wan et al., Journal of Infection, doi:10.1016/j.jinf.2023.02.029 Molnupiravir and nirmatrelvir-ritonavir reduce mortality risk during post-acute COVID-19 phase
28% lower mortality (p<0.0001), 24% lower hospitalization (p<0.0001), and 18% lower progression (p<0.0001). Retrospective 30,040 hospitalized patients in Hong Kong, showing lower mortality with paxlovid treatment. Patients with contraindications to paxlovid were not excluded.
Feb 10
2023
 Kuroda et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkad027 Efficacy comparison of 3CL protease inhibitors ensitrelvir and nirmatrelvir against SARS-CoV-2 in vitro and in vivo
In vitro and animal study comparing nirmatrelvir and ensitrelvir, showing similar efficacy in vitro, and equal or better efficacy of ensitrelvir in vivo (with similar unbound-drug plasma concentrations).
Feb 9
2023
 Aggarwal et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(23)00011-7 Real-world use of nirmatrelvir–ritonavir in outpatients with COVID-19 during the era of omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study
Retrospective 28,167 patients in the USA demonstrating confounding. The large difference shown in Figure 1 at day 0 indicates that the groups are not comparable (32 control hospitalizations versus 0 for paxlovid at day 0) and suggests imm..
Feb 8
2023
 Boretti, A., Clinical and Experimental Medicine, doi:10.1007/s10238-023-01010-7 On the choice of Molnupiravir and Paxlovid as the only antivirals permitted for COVID-19 infection in Australia
Letter to the editor discussing the choice of molnupiravir and paxlovid as the only approved COVID-19 antiviral therapies in Australia in 2022, despite other therapies showing higher efficacy and lower cost in clinical trials. The author ..
Feb 5
2023
 Liu et al., The Lancent Regional Health, doi:10.1016/j.lanwpc.2023.100694 Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study
38% lower mortality (p=0.57), 67% higher ventilation (p=0.44), 10% longer ICU admission (p=0.8), and 27% higher progression (p=0.58). RCT 264 patients in China, showing no significant difference in outcomes with paxlovid.
Jan 31
2023
 Shah et al., American Journal of Transplantation, doi:10.1016/j.ajt.2022.12.004 Paxlovid associated with decreased hospitalization rate among adults with COVID-19 — United States, April–September 2022
51% lower hospitalization (p<0.0001). Retrospective 699,848 outpatients with COVID-19 showing lower hospitalization with paxlovid.
Jan 25
2023
 Evans et al., Journal of Infection, doi:10.1016/j.jinf.2023.02.012 Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study
41% lower combined mortality/hospitalization (p=0.04). Retrospective high risk outpatients in the UK, showing lower hospitalization/death with paxlovid treatment. Residual confounding is likely with adjustments having no detail on specific comorbidities. Patients with contraindications for pa..
Jan 22
2023
 Zheng et al., medRxiv, doi:10.1101/2023.01.20.23284849 Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform
4% higher combined mortality/hospitalization (p=0.91). OpenSAFELY retrospective 7,683 outpatients in the UK, showing no significant difference in hospitalization/death between paxlovid and sotrovimab.
Jan 16
2023
 Ganipisetti et al., Cureus, doi:10.7759/cureus.33831 Paxlovid-Induced Symptomatic Bradycardia and Syncope
Case report of a 71-year-old female who developed symptomatic bradycardia, syncopal episodes, and sinus pause after taking paxlovid (nirmatrelvir/ritonavir) for mild COVID-19 infection.
Jan 11
2023
 Heilmann et al., Science Translational Medicine, doi:10.1126/scitranslmed.abq7360 SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376
In vitro and in silico study showing selection of resistant mutations with nirmatrelvir use. Several mutations were identified that confer resistance to 3CLpro inhibitors nirmatrelvir, ensitrelvir, and GC376. Authors note that most of the..
Jan 10
2023
 Jochmans et al., mBio, doi:10.1128/mbio.02815-22 The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir
In vitro study showing that SARS-CoV-2 can develop resistance to 3CLpro inhibitors, including nirmatrelvir (paxlovid), through a combination of 3CLpro mutations (L50F, E166A, L167F). Authors passaged SARS-CoV-2 in the presence of increasi..
Dec 31
2022
 Cai et al., Journal of Infection, doi:10.1016/j.jinf.2022.10.002 Efficacy of Paxlovid in patients with acute kidney injury who developed COVID-19
9% lower mortality (p=0.83), 30% lower ventilation (p=0.58), 11% lower ICU admission (p=0.55), and 20% shorter hospitalization (p=0.02). Retrospective 104 AKI patients with COVID-19 in China, 61 treated with paxlovid, showing faster viral clearance and shorter hospitalization with treatment, but no significant difference in morality or ICU admission.
Dec 23
2022
 Zhou et al., Science Advances, doi:10.1126/sciadv.add7197 Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system
In vitro study showing that SARS-CoV-2 can develop high-level resistance to the oral protease inhibitor nirmatrelvir while retaining fitness in cell culture. Authors identified combinations of substitutions in the SARS-CoV-2 main protease..
Dec 13
2022
 Dryden-Peterson et al., Annals of Internal Medicine, doi:10.7326/M22-2141 (date from preprint) Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System
71% lower mortality (p=0.006), 44% lower combined mortality/hospitalization (p=0.0001), and 40% lower hospitalization (p=0.001). IPW retrospective 44,551 outpatients age 50+ in the USA, showing lower mortality and hospitalization with paxlovid treatment.
Dec 6
2022
 Bajema et al., medRxiv, doi:10.1101/2022.12.05.22283134 Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes
58% lower mortality (p=0.0004), 56% lower ICU admission (p=0.03), and 7% lower hospitalization (p=0.53). Retrospective 112,380 high-risk patients in the USA, showing lower mortality with paxlovid treatment. The title and headers of Table S14 are conflicting but the data appears to match the title.
Nov 15
2022
 Hoertel et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2022.42140 Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease
Retrospective 62,525 hospitalized COVID-19 patients in France, showing that over 50% of patients that died had a contraindication for the use of paxlovid. Retrospective studies that do not exclude contraindicated patients may significantl..
Nov 15
2022
 Pandit et al., medRxiv, doi:10.1101/2022.11.14.22282195 The Paxlovid Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences Between Paxlovid and Untreated COVID-19 Participants
1% improved recovery (p=0.9), 3% improved viral clearance (p=0.73), and 171% worse results (p=0.06). Prospective study of 170 COVID-19 patients in the USA, showing no significant difference in symptomatic and viral recovery times, and higher risk of symptomatic rebound, without statistical significance. There were more elderly patients i..
Nov 5
2022
 Schwartz et al., medRxiv, doi:10.1101/2022.11.03.22281881 Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada
50% lower mortality (p<0.0001) and 43% lower combined mortality/hospitalization (p<0.0001). Retrospective 177,545 patients in Canada, 8,876 treated with paxlovid, showing lower mortality and hospitalization with treatment, and declining efficacy over the two time periods analyzed.
Oct 8
2022
 Wong et al., The Lancet, doi:10.1016/S0140-6736(22)01586-0 Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study
66% lower mortality (p<0.0001), 38% lower ventilation (p=0.36), 58% higher ICU admission (p=0.08), and 24% lower hospitalization (p<0.0001). PSM retrospective 1,074,856 outpatients in Hong Kong, showing lower mortality and hospitalization with paxlovid.
Oct 7
2022
 Mazzotta et al., Journal of Medical Virology, doi:10.1002/jmv.28186 Viral load decrease in SARS‐CoV‐2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents
Observational study of 521 outpatients with mild-to-moderate COVID-19 showing paxlovid had stronger viral load reduction against Omicron BA.1 and BA.2 variants compared to sotrovimab, molnupiravir, and remdesivir, with the exception of co..
Sep 14
2022
 Zhou et al., medRxiv, doi:10.1101/2022.09.13.22279908 Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study
73% lower mortality (p<0.0001) and 84% lower hospitalization (p<0.0001). Pfizer retrospective 2,811 high risk COVID-19 patients treated with paxlovid in the US, and 10,849 matched controls, showing lower risk of mortality and hospitalization with treatment.
Sep 6
2022
 Zhong et al., Frontiers in Medicine, doi:10.3389/fmed.2022.980002 The efficacy of paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: Results of a non-randomized clinical trial
15% faster recovery (p=0.26) and 16% faster viral clearance (p=0.009). Retrospective 106 paxlovid and 36 control patients in China, showing faster viral clearance with treatment.
Aug 28
2022
 Shao et al., Vaccines, doi:10.3390/vaccines10091409 Clinical Progression and Outcome of Hospitalized Patients Infected with SARS-CoV-2 Omicron Variant in Shanghai, China
20% faster viral clearance (p=0.0006). Retrospective 226 patients in China, showing faster viral clearance with paxlovid. Age range and severity differed between groups.
Aug 20
2022
 Ganatra et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac673 Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19
95% lower mortality (p=0.002), 39% lower progression (p=0.0001), and 56% lower hospitalization (p=0.02). TriNetX retrospective 1,131 vaccinated COVID-19 patients treated with paxlovid and matched controls, showing lower mortality and hospitalization with treatment.
Aug 9
2022
 de Oliveira et al., Research Square, doi:10.21203/rs.3.rs-1915291/v1 H172Y mutation perturbs the S1 pocket and nirmatrelvir binding of SARS-CoV-2 main protease through a nonnative hydrogen bond
In silico and in vitro study of the H172Y mutation which significantly reduces paxlovid's inhibitory activity. Monotherapy with paxlovid and selective pressure may favor resistance mutations.
Aug 4
2022
 Lu et al., Emerging Microbes & Infections, doi:10.1080/22221751.2022.2109517 Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave
12% improved viral clearance (p=0.02). Retrospective 1,377 patients in China, showing significantly faster viral clearance with Paxlovid. Authors analyze progression to severe/critical disease, but do not provide results for Paxlovid.
Aug 1
2022
 Lim et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac389 Prevalence of Medical Contraindications to Nirmatrelvir/Ritonavir in a Cohort of Hospitalized and Nonhospitalized Patients With COVID-19
Analysis of 66,007 hospitalized and non-hospitalized patients showing a 14% prevalence of medical contraindications with nirmatrelvir/ritonavir for outpatients, 21% for inpatients, and 35% for patients that died.
Jul 23
2022
 Li et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac600 Association of nirmatrelvir/ritonavir treatment on upper respiratory SARS-CoV-2 RT-PCR negative conversion rates among high-risk patients with COVID-19
79% improved viral clearance (p<0.0001). Retrospective 258 paxlovid patients and 224 patients before paxlovid was available in China, showing significantly faster viral clearance with treatment. Adjusted results are only provided for subgroups (≤5, >5 days from onset). Patients ..
Jul 6
2022
 Shao et al., medRxiv, doi:10.1101/2022.07.03.22277169 Clinical advancement of patients infected with SARS-CoV-2 Omicron variant in Shanghai, China
20% faster viral clearance (p=0.0006). Retrospective 17 paxlovid and 114 lianhuaqingwen patients in China, showing faster viral clearance with paxlovid.
Jun 14
2022
 Hammond et al., New England Journal of Medicine, doi:10.1056/NEJMoa2309003 (results released 6/14/2022) Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19
52% lower hospitalization (p=0.2), 12% lower severe cases (p=0.27), 4% lower progression (p=0.21), and 2% faster recovery (p=0.6). Delayed publication for EPIC-SR showing no significant difference in time to sustained alleviation. Selected results were made available in December 2021 and June 2022. Some results are only available in the registry and are missing in th..
Jun 2
2022
 Najjar-Debbiny et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac443 Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients
46% lower severe cases (p=0.0002). Retrospective 180,351 patients in Israel, 4,737 treated with paxlovid, showing significantly lower combined severe COVID-19 / mortality with treatment.
Jun 1
2022
 Arbel et al., New England Journal of Medicine, doi:10.1056/NEJMoa2204919 (date from preprint) Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge
56% lower mortality (p=0.37) and 57% lower hospitalization (p=0.1). Retrospective 109,254 patients in Israel, 3,902 treated with nirmatrelvir, showing lower mortality and hospitalization with treatment for the subgroup of patients >65. Authors only provide subgroup results.
May 24
2022
 Yip et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac687 (date from preprint) Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients
19% lower combined mortality/ICU admission (p=0.45) and 21% lower hospitalization (p=0.01). Propensity score weighted retrospective of 93,883 outpatients in Hong Kong, 5,808 treated with molnupiravir and 4,921 treated with paxlovid, showing higher hospitalization and higher combined mortality/mechanical ventilation/ICU admission..
May 20
2022
 Wong et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(22)00507-2 (date from preprint) Real-world effectiveness of early molnupiravir or nirmatrelvir–ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study
66% lower mortality (p<0.0001), 3% lower ventilation (p=0.96), 43% lower progression (p<0.0001), and 4% shorter hospitalization (p=0.32). PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with paxlovid treatment.
Apr 29
2022
 Pfizer, Press Release Pfizer Shares Top-Line Results from Phase 2/3 EPIC-PEP Study of PAXLOVID™ for Post-Exposure Prophylactic Use
25% lower severe cases (p=0.42), 15% lower progression (p=0.2), and 36% fewer symptomatic cases (p=0.12). PEP RCT showing no significant difference with paxlovid post-exposure prophylaxis. Results from [classic.clinicaltrials.gov].
Apr 4
2022
 Ledford et al., Nature, doi:10.1038/d41586-022-00919-5 African clinical trial denied access to key COVID drug Paxlovid
News reporting that Pfizer denied access to Paxlovid for an independent trial. The press release indicates that Pfizer has denied access for multiple groups [ANTICOV]. Also see [twitter.com].
Mar 15
2022
 ANTICOV, Press Release Pfizer blocking research to generate evidence on optimal use of novel antiviral for COVID-19 patients in low- and middle-income countries
ANTICOV reports that Pfizer has denied access to paxlovid for studies proposed by multiple groups. Also see [Ledford].
Feb 16
2022
 Hammond et al., New England Journal of Medicine, doi:10.1056/NEJMoa2118542 Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19
96% lower mortality (p=0.0005), 88% lower hospitalization (p<0.0001), 11% higher progression (p=0.45), and 17% improved recovery (p=0.002). EPIC-HR RCT, 1,039 higher risk patients treated with paxlovid (PF-07321332 + ritonavir) and 1,046 control patients, showing significantly lower mortality and hospitalization with treatment. Some results were reported later in [Hammond], ..
Dec 14
2021
 Pfizer, Press Release Pfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk or hospitalization or death
70% lower hospitalization (p=0.05). EPIC-SR trial interim results, 428 patients treated with paxlovid (PF-07321332 + ritonavir) and 426 control patients, showing lower hospitalization with treatment. NCT05011513.
Nov 30
2021
 Ullrich et al., bioRxiv, doi:10.1101/2021.11.28.4702264 Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332
In vitro study showing that PF-07321332 maintains efficacy against variants C.37 lambda, B.1.1.318, B.1.2, B.1.351 beta, and P.2 zeta.
Nov 5
2021
 Abdelnabi et al., bioRxiv, doi:10.1101/2021.11.04.467077 The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
In vitro and hamster study showing paxlovid component PF-07321332 effective against four variants of concern, inibits replication of the alpha variant in primary human airway epithelial cells, protected Syrian hamsters against intranasal ..
Jul 30
2021
 Tang et al., International Journal of Clinical Pharmacy, doi:10.1007/s11096-021-01311-5 Drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19: a disproportionality analysis of U.S. food and drug administration adverse event reporting system (FAERS) data
Disproportionality analysis showing higher risk of liver injury with lopinavir/ritonavir for COVID-19 patients. Paxlovid combines nirmatrelvir and ritonavir.
Aug 22
2002
 Zhong et al., Arteriosclerosis, Thrombosis, and Vascular Biology, doi:10.1161/01.atv.0000034707.40046.02 HIV Protease Inhibitor Ritonavir Induces Cytotoxicity of Human Endothelial Cells
In vitro study showing that ritonavir (part of paxlovid) can cause endothelial mitochondrial DNA damage and cell death at concentrations near clinical plasma levels.
References