Summary of COVID-19 paxlovid studies

148 patient paxlovid late treatment PSM 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 2024, Infections in the immunosuppressed and immunocompromised host, https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A2917, https://c19p.org/liu23pl

2. Zhu et al., Clinical characteristics and risk factors of non-mild outcomes in patients with Omicron variant COVID-19 in Shanghai, China

311 patient paxlovid early treatment study: 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 2024, The J. Infection in Developing Countries, https://www.jidc.org/index.php/journal/article/view/18138, https://c19p.org/zhu5

3. Liu et al., Clinical characteristics, outcomes, and risk factors of SARS-CoV-2 breakthrough infections among 572 fully vaccinated (BBIBP-CorV) hospitalized patients

572 patient paxlovid late treatment study: 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 analysis of confounding are not provided. The results for paxlovid can be compared with the alternative antiviral azvudine, which shows lower risk (without statistical significance). Paxlovid was not included in the multivariable analysis (only combined antiviral therapy was used without explanation).
Oct 2023, Heliyon, https://www.sciencedirect.com/science/article/pii/S240584402308595X, https://c19p.org/liu13

4. Deng et al., Effectiveness of Paxlovid in the treatment of the SARS-CoV-2 Omicron variant infection in children with hematologic malignancies: a retrospective cohort study

42 patient paxlovid early treatment PSM study: 17% slower viral clearance (p=0.71) and 105% worse results (p=0.57).
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 2024, Translational Cancer Research, https://tcr.amegroups.com/article/view/88997/html, https://c19p.org/deng4

5. Horby et al., Molnupiravir or nirmatrelvir-ritonavir versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

137 patient paxlovid early treatment RCT: 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, which may in part be due to side effects of treatment. The treatment delay was notably shorter compared to other treatments in this trial - 4 and 5 days from onset for paxlovid and molnupiravir. There was an exactly one year delay in publication after completion of recruitment. No press release or results are shown on the trial web site. In contrast, a press release was issued for the HCQ arm on the same day that recruitment ended. The one year delay may be a maximum delay due to EU Clinical Trials registration and associated regulatory requirements for the release of results within 12 months.
May 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.05.23.24307731v1, https://c19p.org/horbypl

6. Dian et al., Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities

2,118 patient paxlovid late treatment PSM study: 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 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323002906, https://c19p.org/dianpl

7. Edelstein et al., SARS-CoV-2 virologic rebound with nirmatrelvir-ritonavir therapy

127 patient paxlovid early treatment study: 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-competent virus. When compared with previous studies, authors believe the higher frequency of rebound detected is due to the frequent sampling and culture analysis. When authors restrict to 3 timepoints with PCR only, as in prior studies, they detect a similar rate of rebound as in previous studies, but miss 80% of rebound events detected in this study.
Jun 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.06.23.23288598, https://c19p.org/edelstein

8. Yu et al., 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

208 patient paxlovid late treatment RCT: 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 2023, Phytomedicine, https://www.sciencedirect.com/science/article/pii/S0944711323003860, https://c19p.org/yu4

9. Lin et al., Clinical outcomes of nirmatrelvir-ritonavir use in pregnant women during the Omicron wave of the coronavirus disease 2019 pandemic

85 patient paxlovid early treatment study: 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 consecutive days were excluded.
Oct 2023, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034123003349, https://c19p.org/lin3

10. Lv et al., Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study

324 patient paxlovid late treatment 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 2023. Adjusted results are only provided for all antivirals combined, however the results are similar before and after adjustment. Multivariable Cox regression analysis for all antivirals combined showed an adjusted hazard ratio for mortality of 6.06, p=0.099. While adjustment includes factors related to baseline severity, there may be residual confounding by indication.
Jun 2024, J. Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199089/, https://c19p.org/lv3pl

11. Peng et al., Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer

166 patient paxlovid late treatment study: 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 2024, Technology in Cancer Research & Treatment, https://journals.sagepub.com/doi/10.1177/15330338241248573, https://c19p.org/peng4

12. Low et al., Nirmatrelvir/ritonavir treatment and the risk of post-COVID condition over 180 days in Malaysia

2,524 patient paxlovid long COVID study: 30% higher PASC (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 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09679-1, https://c19p.org/low3

13. Durstenfeld et al., Association of nirmatrelvir for acute SARS‐CoV‐2 infection with subsequent Long COVID symptoms in an observational cohort study

4,684 patient paxlovid long COVID 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.
Jan 2024, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.29333, https://c19p.org/durstenfeld

14. Lu et al., Clinical Characteristics of Severe COVID-19 Patients During Omicron Epidemic and a Nomogram Model Integrating Cell-Free DNA for Predicting Mortality: A Retrospective Analysis

282 patient paxlovid late treatment study: 6% higher mortality (p=0.84).
Retrospective 282 severe COVID-19 patients, showing no significant difference in mortality with paxlovid in unadjusted results.
Oct 2023, Infection and Drug Resistance, https://www.dovepress.com/clinical-characteristics-of-severe-covid-19-patients-during-omicron-ep-peer-reviewed-fulltext-article-IDR, https://c19p.org/lu3

15. Guo et al., 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

1,978 patient paxlovid late treatment 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 2023, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08620-2, https://c19p.org/guo3

16. Fu et al., Comparison of the Different Medications for COVID-19 in Kidney Transplant Recipients

111 patient paxlovid late treatment study: 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 2023, Authorea, Inc., https://www.authorea.com/users/632878/articles/651497-comparison-of-the-different-medications-for-covid-19-in-kidney-transplant-recipients?commit=ab4741e389c91904de90a9ce527e183d368e45d0, https://c19p.org/fu2

17. Liu et al., Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

264 patient paxlovid early treatment RCT: 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.
Feb 2023, The Lancent Regional Health, https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(23)00012-3/fulltext, https://c19p.org/liu6

18. Wei et al., 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

725 patient paxlovid late treatment study: 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 azvudine was associated with lower ICU admission and invasive ventilation use.
Oct 2023, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2023.1274294/full, https://c19p.org/wei2pl

19. Zhou et al., Secondary pulmonary infection and co-infection in elderly COVID-19 patients during the pandemics in a tertiary general hospital in Beijing, China

322 patient paxlovid late treatment study: 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 paxlovid can be compared with the alternative antiviral azvudine. Azvudine shows lower risk, suggesting higher risk with paxlovid use. Authors note the potential for increased risk with paxlovid due to serious adverse events related to drug-drug interactions, which may be more significant within the elderly population.
Oct 2023, Frontiers in Microbiology, https://www.frontiersin.org/articles/10.3389/fmicb.2023.1280026/full, https://c19p.org/zhou13

20. Zheng et al., 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

7,683 patient paxlovid early treatment study: 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 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.20.23284849, https://c19p.org/zheng5

21. Pandit et al., The Paxlovid Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences Between Paxlovid and Untreated COVID-19 Participants

170 patient paxlovid early treatment study: 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 in the paxlovid group. 5 paxlovid patients did not test negative during the 16 day daily followup, compared to zero for control. Only patients testing negative or reporting no symptoms were included in the recovery time analyses. KM curves show no significant difference in viral or symptomatic recovery.
Nov 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.11.14.22282195, https://c19p.org/pandit

22. Li et al., Clinical efficacy analysis of paxlovid in children with hematological diseases infected with the omicron SARS-CoV-2 new variant

20 patient paxlovid early treatment study: 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 2023, Frontiers in Pediatrics, https://www.frontiersin.org/articles/10.3389/fped.2023.1160929/full, https://c19p.org/li24

23. Preiss et al., Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C

426,352 patient paxlovid long COVID study: 2% lower PASC (p=0.2).
Retrospective study of 426,352 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 used a large, nationally representative sample and a machine learning model to identify PASC cases.
Jan 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.01.20.24301525, https://c19p.org/preiss

24. Yang et al., Reduced Viral Shedding Time in High-Risk COVID-19 Patients Infected by Omicron and Treated with Paxlovid: A Real-World Study from China

1,086 patient paxlovid early treatment study: no change in viral clearance (p=0.96).
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 the time to events and can handle censored data, and may be more clinically meaningful because they directly relate to the instantaneous risk of an event occurring. Authors do not discuss the large difference between the Cox and logistic regression results, which may bre related to increased rebound with paxlovid, time-dependent treatment effects, baseline differences, censored data, and unmeasured confounding.
Mar 2024, Infection and Drug Resistance, https://www.dovepress.com/reduced-viral-shedding-time-in-high-risk-covid-19-patients-infected-by-peer-reviewed-fulltext-article-IDR, https://c19p.org/yang14

25. Wang et al., Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study

249 patient paxlovid early treatment 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 treatment. Early viral decline was faster with paxlovid, without statistical significance.
Feb 2024, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537024000476, https://c19p.org/wang25pl

26. Ioannou et al., Effectiveness of Nirmatrelvir–Ritonavir Against the Development of Post–COVID-19 Conditions Among U.S. Veterans

19,186 patient paxlovid long COVID PSM study: 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 specific conditions (venous thromboembolism and pulmonary embolism) however this was not significant after adjustment for baseline medications which constitute drug-drug interactions or contraindications to nirmatrelvir-ritonavir. This analysis should be more accurate than many paxlovid retrospective studies. Many studies are biased due to inclusion of patients with contraindications to paxlovid, and due to confounding by treatment propensity, as below. Authors account for contraindications (though not all would be identified) and partially account for treatment propensity by including the frequency of health care encounters in matching.
Oct 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M23-1394, https://c19p.org/ioannou

27. Li et al., 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

223 patient paxlovid late treatment study: 18% lower mortality (p=0.61).
Retrospective 223 hospitalized patients in China, showing no significant difference in mortality with paxlovid in unadjusted results.
Sep 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1238713/full, https://c19p.org/li25

28. Park et al., 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

2,507 patient paxlovid early treatment study: 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 confounding in paxlovid population studies since the standard of care and treatment propensity for additional treatments is likely to be more similar for this population. Treatment delay is unknown and authors note that treatment may have been delayed. In most population studies patients receiving paxlovid may have more contact with the medical system, be more likely to follow other recommendations, be more likely to receive additional care, and be more likely to take additional treatments that are not tracked in the data (e.g., nasal/oral hygiene, vitamin D, etc.).
Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3003449/v1, https://c19p.org/park4

29. Shao et al., Clinical advancement of patients infected with SARS-CoV-2 Omicron variant in Shanghai, China

131 patient paxlovid early treatment study: 20% faster viral clearance (p=0.0006).
Retrospective 17 paxlovid and 114 lianhuaqingwen patients in China, showing faster viral clearance with paxlovid.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.03.22277169, https://c19p.org/shao

30. Dalton et al., 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

paxlovid early treatment PSM study: 8% lower PASC (p<0.0001).
Retrospective 874,299 COVID-19 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 2023, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofad500.2468/7448238, https://c19p.org/dalton

31. Yang et al., Clinical Prognosis and Risk Factors of Death for Covid-19 Patients Complicated with Coronary Heart Disease/Diabetes/Hypertension-A Retrospective, Real-World Study

1,281 patient paxlovid early treatment study: 2% lower mortality (p=0.04).
Retrospective 1,281 COVID-19 patients with comorbidities in China, showing 2% lower mortality with paxlovid.
Jun 2023, Elsevier BV, https://www.ssrn.com/abstract=4488145, https://c19p.org/yang5

32. Shao et al., Clinical Progression and Outcome of Hospitalized Patients Infected with SARS-CoV-2 Omicron Variant in Shanghai, China

131 patient paxlovid early treatment study: 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 2022, Vaccines, https://www.mdpi.com/2076-393X/10/9/1409, https://c19p.org/shao2

33. Shao et al., Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China

789 patient paxlovid late treatment study: 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 significantly lower for paxlovid patients at 60 days.
Jul 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/7/1859, https://c19p.org/shao4

34. Shao et al., Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China

1,082 patient paxlovid late treatment study: 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 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.10.23289325v1, https://c19p.org/shao3

35. Fung et al., Nirmatrelvir and Molnupiravir and Post–COVID-19 Condition in Older Patients

305,275 patient paxlovid long COVID study: 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 the actual efficacy due to likely lower average severity of the additional treatment patients included based on home tests.
Oct 2023, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2811092, https://c19p.org/fung2pl

36. Yen et al., Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan

2,196 patient paxlovid early treatment study: 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 the study in Taiwan.
Aug 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09654-w, https://c19p.org/yen2pl

37. Lewnard et al., 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

133,426 patient paxlovid early treatment study: 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 indication, healthcare seeking behavior, knowledge of COVID-19 treatments, etc. is likely significant. Authors partially address this in their matching procedure. Notably, authors do not appear to address confounding by contraindication, and matching is unable to find a match for patients that seek adjuvant treatments (e.g., paxlovid + vitamin D). Confounding may be more significant for patients that seek care earlier.
Mar 2023, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309923001184, https://c19p.org/lewnard

38. Dormuth et al., Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications

6,866 patient paxlovid early treatment study: 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 contraindicated patients, and do not address confounding by adjuvant treatments, therefore the results are expected to overestimate benefit. (Exclusions are not clear - the paper notes exclusion for severe kidney disease, but this is not in the detailed exclusion list in the appendix, while it is in the inclusion list for CEV2. Contraindications to paxlovid are not mentioned). Confounding may potentially remove all of the benefit seen. The worse results for protection against ER visits is consistent with the confounding being significant - the overestimation of benefit due to confounding based on inclusion of contraindicated patients is expected to increase for more severe outcomes.
Oct 2023, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2809972, https://c19p.org/dormuth

39. Zhong et al., The efficacy of paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: Results of a non-randomized clinical trial

142 patient paxlovid early treatment study: 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.
Sep 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.980002/full, https://c19p.org/zhong4

40. Chen et al., Nirmatrelvir and ritonavir combination against COVID‐19 caused by omicron BA.2.2 in the elderly: A single‐center large observational study

648 patient paxlovid late treatment PSM study: no change in mortality (p=1), 80% lower ventilation (p=0.22), no change in severe cases (p=1), and 27% lower need for oxygen therapy (p=0.64).
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 faster viral clearance. There was no significant difference in mortality, progression to critical illness, or need for oxygen therapy.
Apr 2024, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1232, https://c19p.org/chen20

41. Lai et al., Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study

9,553 patient paxlovid late treatment 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 2024, Age and Ageing, https://academic.oup.com/ageing/article/doi/10.1093/ageing/afae180/7733454, https://c19p.org/lai2pl

42. Shah et al., Paxlovid associated with decreased hospitalization rate among adults with COVID-19 — United States, April–September 2022

699,848 patient paxlovid early treatment study: 51% lower hospitalization (p<0.0001).
Retrospective 699,848 outpatients with COVID-19 showing lower hospitalization with paxlovid.
Jan 2023, American J. Transplantation, https://www.sciencedirect.com/science/article/pii/S160061352229279X, https://c19p.org/shah7

43. Lu et al., Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave

paxlovid early treatment study: 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 2022, Emerging Microbes & Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2022.2109517, https://c19p.org/lu

44. Choi et al., Comparative Efficacy of Combination Treatment with Nirmatrelvir-Ritonavir and Remdesivir Versus Remdesivir Monotherapy in Hospitalised COVID-19 Patients: A Target Trial Emulation Study

1,843 patient paxlovid early treatment 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 2024, SSRN, https://www.ssrn.com/abstract=4683854, https://c19p.org/choi5

45. Patel et al., Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir

2,008 patient paxlovid early treatment PSM study: 20% lower PASC (p=0.01).
TriNetX retrospective 1,004 paxlovid patients and matched controls, showing lower risk of PASC with treatment.
Apr 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.04.05.23288196, https://c19p.org/patel6

46. Wee et al., 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

143,698 patient paxlovid early treatment study: 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 2023, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X2300294X, https://c19p.org/wee

47. Yip et al., Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients

88,075 patient paxlovid early treatment study: 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 with molnupiravir, without statistical significance; and lower hospitalization and combined mortality/mechanical ventilation/ICU admission with paxlovid, statistically significant only for hospitalization.
May 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac687/6678124, https://c19p.org/yippl

48. Wan et al., Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Hospitalized Patients With COVID-19

7,119 patient paxlovid late treatment study: 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 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M22-3057, https://c19p.org/wan2pl

49. Low et al., 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

31,483 patient paxlovid early treatment PSM 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 2023, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971223006884, https://c19p.org/low4

50. Arbel et al., Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge

109,213 patient paxlovid early treatment study: 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 2022, New England J. Medicine, http://www.nejm.org/doi/10.1056/NEJMoa2204919, https://c19p.org/arbel

51. Pfizer et al., A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir

436 patient paxlovid late treatment RCT: 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 2024, Pfizer, NCT05567952, https://clinicaltrials.gov/study/NCT05567952, https://c19p.org/pfizerpl

52. Henderson et al., COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina

44,671 patient paxlovid early treatment study: 84% lower hospitalization (p=0.002).
EHR retrospective 44, 671 patients with 4,948 receiving paxlovid, showing lower hospitalization with treatment.
Feb 2024, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkae042/7611865, https://c19p.org/henderson2

53. Cai et al., Efficacy of Paxlovid in patients with acute kidney injury who developed COVID-19

104 patient paxlovid early treatment study: 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 2022, J. Infection, https://www.sciencedirect.com/science/article/pii/S016344532200562X, https://c19p.org/cai2

54. Cheng et al., Effectiveness of molnupiravir and nirmatrelvir–ritonavir in CKD patients with COVID-19

4,128 patient paxlovid early treatment study: 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 ventilatory support. Notably, there is no estimated benefit for ventilatory support, the outcome most directly related to severe COVID-19. The very large difference in vaccine uptake suggests major confounding issues, for example treatment decisions based on vaccine uptake, or confounding by time where control patients are more likely from earlier periods with lower vaccine uptake, which may also correspond to more dangerous variants.
Feb 2024, Kidney Int. Reports, https://www.sciencedirect.com/science/article/pii/S2468024924000986, https://c19p.org/cheng4pl

55. Ganatra et al., Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19

2,260 patient paxlovid early treatment PSM study: 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 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac673/6672670, https://c19p.org/ganatra

56. Evans et al., 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

5,575 patient paxlovid early treatment 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 paxlovid were not excluded.
Jan 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323000828, https://c19p.org/evans2

57. Najjar-Debbiny et al., Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients

180,351 patient paxlovid early treatment study: 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 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac443/6599020, https://c19p.org/najjardebbiny

58. Dryden-Peterson et al., Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System

44,045 patient paxlovid early treatment study: 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 2022, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M22-2141, https://c19p.org/drydenpeterson

59. Schwartz et al., Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada

177,545 patient paxlovid early treatment study: 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.
Nov 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.11.03.22281881, https://c19p.org/schwartz4

60. Bajema et al., 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

3,174 patient paxlovid early treatment PSM study: 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.
Dec 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.12.05.22283134, https://c19p.org/bajema

61. Xu et al., 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

320 patient paxlovid early treatment study: 12% shorter hospitalization (p=0.09), 35% faster recovery (p<0.0001), 58% faster viral clearance (p<0.0001), and 47% lower PASC (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-covid condition but not for the main outcomes.
Dec 2023, Medicine, https://journals.lww.com/10.1097/MD.0000000000036714, https://c19p.org/xu10

62. Yan et al., Nirmatrelvir/ritonavir for patients with SARS-CoV-2 infection and impaired kidney function during the Omicron surge

195 patient paxlovid early treatment study: 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 2023, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2023.1147980/full, https://c19p.org/yan2

63. Choi et al., 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

4,540 patient paxlovid early treatment 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 with remdesivir + paxlovid compared with remdesivir alone. Patients were treated within 5 days of diagnosis, however the time from onset is not known.
Jul 2024, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309924003530, https://c19p.org/choi7pl

64. Kim et al., Effectiveness of Paxlovid, an Oral Antiviral Drug, Against the Omicron BA.5 Variant in Korea: Severe Progression and Death Between July and November 2022

1,936,925 patient paxlovid early treatment study: 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.
Jul 2023, J. Korean Medical Science, https://jkms.org/DOIx.php?id=10.3346/jkms.2023.38.e211, https://c19p.org/kim13

65. Li et al., Association of nirmatrelvir/ritonavir treatment on upper respiratory SARS-CoV-2 RT-PCR negative conversion rates among high-risk patients with COVID-19

399 patient paxlovid early treatment study: 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 that discontinued treatment due to side effects were excluded. The treatment and control groups were separated in time. Control patients were hospitalized later, median 3 days [2-5] vs. 2 [1-3] for paxlovid patients. Authors report some rebound events, but may not have monitored all patients for rebound. Authors report testing daily until negative conversion and it is unclear how many or when patients were tested after conversion.
Jul 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac600/6649232, https://c19p.org/li16

66. Wan et al., Molnupiravir and nirmatrelvir-ritonavir reduce mortality risk during post-acute COVID-19 phase

23,887 patient paxlovid late treatment study: 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 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323001172, https://c19p.org/wan

67. Zhou et al., 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

13,657 patient paxlovid early treatment PSM 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 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.09.13.22279908, https://c19p.org/zhou8

68. Wong et al., 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

60,214 patient paxlovid early treatment PSM 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 2022, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673622015860, https://c19p.org/wong5

69. Wong et al., 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

1,780 patient paxlovid early treatment PSM 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.
May 2022, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309922005072, https://c19p.org/wong3pl

70. Pfizer et al., Pfizer Shares Top-Line Results from Phase 2/3 EPIC-PEP Study of PAXLOVID™ for Post-Exposure Prophylactic Use

2,954 patient paxlovid prophylaxis RCT: 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 2022, Pfizer, Press Release, https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-top-line-results-phase-23-epic-pep-study, https://c19p.org/pfizerpep

71. Pfizer et al., Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR)

1,288 patient paxlovid early treatment RCT: 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 (until April 2024) EPIC-SR trial.
Jun 2022, Pfizer, NCT05011513, https://clinicaltrials.gov/study/NCT05011513?tab=results, https://c19p.org/epicsr

72. Hammond et al., Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19

2,085 patient paxlovid early treatment RCT: 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], and some results are only available in the registry.
Feb 2022, New England J. Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2118542, https://c19p.org/hammond

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