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

Kim et al., Journal of Korean Medical Science, doi:10.3346/jkms.2023.38.e211

Jul 2023

Retrospective 1,936,925 COVID-19 patients in South Korea, showing lower mortality with paxlovid.

Confounding by treatment propensity. This study analyzes a population where only a fraction of eligible patients received the treatment. Patients receiving treatment may be more likely to follow other recommendations, more likely to receive additional care, and more likely to use additional treatments that are not tracked in the data (e.g., nasal/oral hygiene c19early.org, c19early.org (B), vitamin D c19early.org (C), etc.) — either because the physician recommending paxlovid also recommended them, or because the patient seeking out paxlovid is more likely to be familiar with the efficacy of additional treatments and more likely to take the time to use them. Malden et al. confirm significant bias in the use of paxlovid, showing that treated patients are more likely to be from affluent neighborhoods, be more health-conscious, and have better access to care. Therefore, these kind of studies may overestimate the efficacy of treatments.

Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid Hoertel. 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.

Important missing comments or errors? Let us know.

risk of death, 31.1% lower, RR 0.69, p < 0.001, adjusted per study, odds ratio converted to relative risk, multivariable, model 3.

risk of severe case, 43.1% lower, RR 0.57, p < 0.001, adjusted per study, odds ratio converted to relative risk, multivariable, model 3.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Kim et al., 10 Jul 2023, retrospective, South Korea, peer-reviewed, 5 authors, study period 1 July, 2022 - 30 November, 2022. Contact: sea2sky@korea.kr.

This Paper Paxlovid All

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

Jong Mu Kim, Min-Gyu Yoo, Soon Jong Bae, Jungyeon Kim, MD Hyungmin Lee

Journal of Korean Medical Science, doi:10.3346/jkms.2023.38.e211

Background: Paxlovid is an oral antiviral drug that received emergency use authorization in South Korea for the treatment of patients with mild-to-moderate coronavirus disease 2019 (COVID-19) on January 14, 2022. Since the onset of the severe acute respiratory syndrome coronavirus 2 pandemic, the virus has continued to evolve. The emergence of new variants has raised concerns about possible reductions in the effectiveness of vaccines and drugs. The effectiveness of Paxlovid in patients infected with the omicron variant and subvariants has not yet been determined. This study assessed the effectiveness of Paxlovid at reducing the risk of severe/critical illness or death and death in patients with mild-to-moderate COVID-19 caused by omicron subvariant BA.5. Methods: In this nationwide retrospective cohort study, data on 8,902,726 patients were collected from four sources (the Drug Utilization Review database, COVID-19 Patient Information Management System, confirmed patient information, and basic epidemiological investigation data) between July 1 and November 30, 2022. Multivariable logistic regression analysis was conducted, with adjustment for age, sex, severe acute respiratory syndrome coronavirus 2 immunity (vaccination), and comorbidities. Results: A total of 1,936,925 patients with COVID-19 were included in the analysis, including 420,996 patients treated with Paxlovid, and 1,515,959 patients not treated with Paxlovid. Paxlovid treatment in patients aged ≥ 60 years of age was associated with significantly reduced risk of severe/critical illness or death (46.0%), and death rate (32.5%), and its effectiveness was high, regardless of vaccination status. Conclusion: Paxlovid is effective at reducing the risk of death due to COVID-19 in patients with omicron BA.5 infection, especially in older patients, regardless of vaccination status. This suggests that older patients with COVID-19-related symptoms should be administered Paxlovid, regardless of their vaccination status, to reduce severity and risk of death.

Ethics statement The present study protocol was reviewed and approved by the Institutional Review Board of the Korean National Institute of Health and the requirement for informed consent waived (approval No. 2022-12-02-PE-A).

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