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c19early.org COVID-19 treatment researchPaxlovidPaxlovid (more..)
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0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ EPIC-HR Hammond (DB RCT) 96% 0.04 [0.00-0.68] death 0/1,039 12/1,046 Improvement, RR [CI] Treatment Control Wong (PSM) 66% 0.34 [0.23-0.50] death 890 (n) 890 (n) Yip (PSW) 19% 0.81 [0.47-1.39] death/ICU Arbel 56% 0.44 [0.08-2.59] death Najjar-Debbiny 46% 0.54 [0.39-0.75] severe case population-based cohort Pfizer (DB RCT) 67% 0.33 [0.01-8.08] death 0/654 1/634 Shao 20% 0.80 [0.71-0.91] viral time 17 (n) 114 (n) OT​1 Li (ES) 79% 0.21 [0.15-0.28] viral+ 18/175 130/224 Lu 12% 0.88 [0.78-0.98] viral+ n/a n/a Ganatra (PSM) 95% 0.05 [0.00-0.81] death 0/1,130 10/1,130 confounding Shao 20% 0.80 [0.71-0.91] viral time 17 (n) 114 (n) OT​1 Zhong 15% 0.85 [0.65-1.13] recov. time 106 (n) 36 (n) Zhou (PSM) 73% 0.27 [0.13-0.58] death 7/2,808 100/10,849 Wong (PSM) 66% 0.34 [0.22-0.52] death Schwartz (PSW) 50% 0.50 [0.41-0.61] death population-based cohort Pandit 1% 0.99 [0.83-1.17] no recov. n/a n/a Bajema (PSM) 58% 0.42 [0.26-0.67] death 20/1,587 48.6/1,587 Dryden-Peterson 71% 0.29 [0.12-0.71] death confounding Zheng (PSW) -4% 1.04 [0.56-1.93] death/hosp. 4,836 (n) 2,847 (n) OT​1 Evans 41% 0.59 [0.36-0.97] death/hosp. 602 (n) 4,973 (n) Shah 51% 0.49 [0.46-0.53] hosp. population-based cohort confounding Liu (RCT) 38% 0.62 [0.21-1.86] death 5/132 8/132 Lewnard 84% 0.16 [0.03-0.81] death/ICU n/a n/a confounding Yan 31% 0.69 [0.30-1.58] death 7/73 17/122 Patel (PSM) 20% 0.80 [0.67-0.95] PASC 1,004 (n) 1,004 (n) Li -51% 1.51 [1.11-2.05] recov. time 9 (n) 11 (n) Park 5% 0.95 [0.57-1.62] death 940 (n) 1,567 (n) Wee 14% 0.86 [0.48-1.55] severe case population-based cohort Yang 2% 0.98 [0.95-1.00] death 220 (n) 1,061 (n) POSITIVES Edelstein -761% 8.61 [1.13-34.2] rebound 15/72 1/55 Kim 31% 0.69 [0.63-0.75] death population-based cohort Dormuth 29% 0.71 [0.54-0.93] death/hosp. 85/3,433 120/3,433 confounding Lin -633% 7.33 [0.86-62.7] oxygen 4/30 1/55 Dalton (PSM) 8% 0.92 [0.91-0.93] PASC population-based cohort Fung 7% 0.93 [0.92-0.94] PASC population-based cohort LONG COVID Ioannou (PSM) 1% 0.99 [0.95-1.03] PASC 9,593 (n) 9,593 (n) LONG COVID Durstenfeld (PSW) -14% 1.14 [0.83-1.54] PASC 57/353 176/1,258 LONG COVID Choi 37% 0.63 [0.46-0.86] death 251 (n) 1,592 (n) Preiss 1% 0.99 [0.96-1.01] PASC population-based cohort LONG COVID Zhu -79% 1.79 [1.39-2.33] viral+ 138 (n) 155 (n) Cheng 22% 0.78 [0.60-1.00] death 2,083 (n) 2,045 (n) Wang 13% 0.87 [0.46-1.63] death 66 (n) 55 (n) Henderson 84% 0.16 [0.05-0.50] hosp. confounding Tau​2 = 0.01, I​2 = 94.1%, p < 0.0001 Early treatment 21% 0.79 [0.75-0.83] 218/32,258 624.6/46,582 21% lower risk Li 32% 0.68 [0.47-0.98] viral+ 40/83 130/224 Improvement, RR [CI] Treatment Control Wan 28% 0.72 [0.62-0.84] death 541/6,604 2,541/17,283 Wan 23% 0.77 [0.66-0.90] death 1,813 (n) 5,306 (n) Shao 29% 0.71 [0.44-1.14] death 280 (n) 802 (n) Fu -280% 3.80 [0.41-35.4] ventilation 3/49 1/62 OT​1 Shao 29% 0.71 [0.44-1.14] death 280 (n) 509 (n) Yu (RCT) -2% 1.02 [0.21-4.93] severe case 3/103 3/105 OT​1 Dian (PSM) -175% 2.75 [0.89-8.51] death 11/228 4/228 OT​1 Li 18% 0.82 [0.47-1.43] death 14/73 35/150 Zhou -39% 1.39 [1.02-1.89] death 52/132 54/190 Wei 0% 1.00 [0.68-1.46] death 36/264 63/461 OT​1 Guo -10% 1.10 [1.01-1.20] viral time 779 (n) 1,199 (n) Lu -6% 1.06 [0.77-1.47] death 17/29 140/253 Liu -94% 1.94 [1.24-3.03] progression 27/145 41/427 Tau​2 = 0.07, I​2 = 83.6%, p = 0.65 Late treatment 4% 0.96 [0.80-1.15] 744/10,862 3,012/27,199 4% lower risk Pfizer (DB RCT) 67% 0.33 [0.01-8.20] hosp. 0/830 1/840 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.51 Prophylaxis 67% 0.33 [0.01-8.20] 0/830 1/840 67% lower risk All studies 17% 0.83 [0.79-0.87] 962/43,950 3,637.6/74,621 17% lower risk Paxlovid COVID-19 studies c19early.org March 2024 Tau​2 = 0.01, I​2 = 92.6%, p < 0.0001 Effect extraction pre-specified(most serious outcome) 1 OT: comparison with other treatment Favors paxlovid Favors control
Pfizer has denied access to Paxlovid for independent RCTs Ledford. Pfizer RCTs report very good results, while non-Pfizer RCTs show relatively poor results Liu, Yu. Hoertel 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 paxlovid" FDA. Population studies often do not account for the different expected outcomes for the class of patients that seek out and receive early treatment. Paxlovid is a combination of nirmatrelvir and ritonavir. Nirmatrelvir is a first generation SARS-CoV-2 3CL protease inhibitor Bischof. Ritonavir is a HIV drug used to boost the levels of nirmatrelvir in the body by inhibiting its metabolism. Recent:
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Paxlovid has been officially adopted in 43 countries. Submit updates/corrections.
Mar 13
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 2
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 21
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
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
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
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
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 26
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
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 22
Preiss et al., medRxiv, doi:10.1101/2024.01.20.24301525 Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C
1% lower PASC (p=0.45). Retrospective study of 426,461 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 ..
Jan 15
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
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
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 PASC (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..
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..
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 PASC (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 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 PASC (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 11
2023
Dalton et al., IDWeek 2023 Use of Paxlovid for Treatment of Acute COVID-19 and Occurrence of Post-COVID Conditions among Children and Adults at High-Risk for Severe COVID-19, April 1 - December 31, 2022
8% lower PASC (p<0.0001). Retrospective 297,662 paxlovid patients in the USA, showing lower risk of post-COVID conditions for patients 50+, no significant difference for ages 18-49, and higher risk for age 12-17.
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 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 PASC (p=0.01). TriNetX retrospective 1,004 paxlovid patients and matched controls, showing lower risk of PASC with treatment.
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
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 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 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 selection of nirmatrelvir-resistant mutations with a protease inhibitor.
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.
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.
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
Pfizer, NCT05011513 Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR)
52% lower hospitalization (p=0.2), 4% lower progression (p=0.21), 8% faster recovery (p=0.16), and 4% improved viral clearance (p=0.04). Results for the terminated and unpublished EPIC-SR trial.
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 lower risk of cases with treatment, without statistical significance. 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 21% faster recovery (p=0.0003). 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.
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.
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