A retrospective cohort study of Paxlovid efficacy depending on treatment time in hospitalized COVID-19 patients
- University of Hong Kong, Hong Kong
- University of Cambridge, United Kingdom
- Yale University, United States
- The University of Texas at Austin, United States
- University of Hong Kong, China
Abstract
Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0%-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.
Data availability
All data used in this study can be accessed through Github: https://github.com/ZhanweiDU/PaxHK/.
Article and author information
Author details
Benjamin John Cowling
Funding
Innovation and Technology Commission (AIR@InnoHK)
- Zhanwei Du
Health and Medical Research Fund (07210147)
- Zhanwei Du
National Natural Science Foundation of China (82304204)
- Yuan Bai
National Institutes of Health (AI151176)
- Lauren A Meyers
Centers for Disease Control and Prevention (U01IP001136)
- Lauren A Meyers
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- James M McCaw, University of Melbourne, Australia
Ethics
Human subjects: Individual patient-informed consent was not required in this study using anonymized data.
Version history
- Received: May 31, 2023
- Accepted: April 3, 2024
- Accepted Manuscript published: April 16, 2024 (version 1)
Copyright
© 2024, Du et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A retrospective cohort study of Paxlovid efficacy depending on treatment time in hospitalized COVID-19 patients
eLife 13:e89801.
https://doi.org/10.7554/eLife.89801
Further reading
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- Ecology
- Epidemiology and Global Health
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
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- Epidemiology and Global Health
Background:
The aim of our study was to test the hypothesis that the community contact tracing strategy of testing contacts in households immediately instead of at the end of quarantine had an impact on the transmission of SARS-CoV-2 in schools in Reggio Emilia Province.
Methods:
We analysed surveillance data on notification of COVID-19 cases in schools between 1 September 2020 and 4 April 2021. We have applied a mediation analysis that allows for interaction between the intervention (before/after period) and the mediator.
Results:
Median tracing delay decreased from 7 to 3.1 days and the percentage of the known infection source increased from 34–54.8% (incident rate ratio-IRR 1.61 1.40–1.86). Implementation of prompt contact tracing was associated with a 10% decrease in the number of secondary cases (excess relative risk –0.1 95% CI –0.35–0.15). Knowing the source of infection of the index case led to a decrease in secondary transmission (IRR 0.75 95% CI 0.63–0.91) while the decrease in tracing delay was associated with decreased risk of secondary cases (1/IRR 0.97 95% CI 0.94–1.01 per one day of delay). The direct effect of the intervention accounted for the 29% decrease in the number of secondary cases (excess relative risk –0.29 95%–0.61 to 0.03).
Conclusions:
Prompt contact testing in the community reduces the time of contact tracing and increases the ability to identify the source of infection in school outbreaks. Although there are strong reasons for thinking it is a causal link, observed differences can be also due to differences in the force of infection and to other control measures put in place.
Funding:
This project was carried out with the technical and financial support of the Italian Ministry of Health – CCM 2020 and Ricerca Corrente Annual Program 2023.
