Paxlovid: Is It Still Worth the Cost?
May 15, 2025
By Carol A. Kemper, MD, FIDSA
Source: Faust JS, Meyerowitz-Katz G. Is Paxlovid still worth it? Clin Infect Dis. 2024;79:111-114.
Paxlovid is one of the most effective antivirals developed during the COVID-19 years, demonstrating significant reductions in hospitalization and death in higher-risk persons, as well as the time to viral elimination. However, it does not shorten the duration of symptoms, and there is little evidence that Paxlovid reduces the risk of developing long COVID symptoms. In a University of California San Francisco study of vaccinated, non-hospitalized, non-pregnant patients recruited in 2022, long COVID symptoms occurred at 5.4 months in 16% of those who received Paxlovid and in 14% of those who were untreated (P = NS).1 Of those receiving Paxlovid, 21% developed rebound symptoms, although this also was not associated with the development of long COVID symptoms.
Earlier data in support of Paxlovid found statistically significant — and meaningful — reductions in hospitalization and mortality. In the EPIC-HR study published in 2022, the risk of hospitalization and death by day 28 in unvaccinated persons receiving placebo vs. Paxlovid was 6.45% vs. 0.72%, respectively.2 None of the patients who received Paxlovid died, compared with 7/285 patients (2.4%) receiving placebo.
But those unvaccinated patients were recruited in ~2021, and the risk of severe outcomes has since improved, either because of improved population immunity (from vaccination and/or prior infection) or attenuation of newer viral strains. Current Centers for Disease Control and Prevention (CDC) data in March 2025 indicate the rate of hospitalization from COVID is only 2 per 100,000 population and the percent of all deaths in the United States from COVID is 0.8%. Among 130,263 Department of Veterans Affairs patients with COVID-19 between September 2023 and October 2024, the risk of hospitalization and death with newer strains was substantially lower (2.0% vs. 0.03%, respectively) than historical figures.3 The majority of these patients were vaccinated, including two-thirds who had received booster vaccination, although less than one-third received antiviral therapy for their COVID infection.
With this kind of information in mind, is Paxlovid still worth taking? These authors performed a cost-effective analysis. If the EPIC-HR data were used, the cost to prevent one hospitalization in an unvaccinated adult would be US $9,636. As the cost of Paxlovid increases, and the risk of hospitalization and death decreases, this cost-benefit analysis shifts considerably. Using more current figures, the cost to prevent one hospitalization jumps to $232,000 to $278,000. The cost may be as high as $450,000 to prevent one hospitalization in an adult < 65 years of age at lower risk of hospitalization. Among individuals with three or more doses of messenger ribonucleic acid (mRNA) vaccine, the estimated cost may be as high as $485,000 to prevent one hospitalization.
The authors estimate that if all eligible persons in the United States received Paxlovid, and one-fourth of the population developed COVID twice in the next year, the annual cost would be US $28.7 billion. At present, only a fraction of those eligible for Paxlovid seem to be taking it — and the cost has increased to an estimated US $1,390 per course, and availability may be a concern. Last week, I personally experienced one major pharmacy was “out” at three different stores in St. Paul, MN; a prescriber insisted a serum creatinine be obtained before the drug was dispensed, which entailed a separate trip to an urgent care for a blood test at night. And unfortunately, as of December 2025, the federal government will no longer cover the cost of the drug for those receiving Medicare, Medicaid, or those who are uninsured, which pretty much guarantees that only those with insurance will have access to the drug. It seems the best approach is to continue to encourage the use of Paxlovid for those at highest risk for complications — including those without insurance.
Carol A. Kemper, MD, FIDSA, is Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation.
References
- Durstendfeld MS, Peluso MJ, Lin F, et al. Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent long COVID symptoms in an observational cohort study. J Med Virol. 2024;96:e29333.
- Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022;386:1397-1408.
- Choi T, Xie Y, Al-Aly Z, et al. Rates of hospitalization and death due to COVID-19 in US veterans with SARS-CoV-2 infection in the XBB-, JN.1-, and KP-predominant eras. Open Forum Infect Dis. 2025;12:ofaf115.
Paxlovid is one of the most effective antivirals developed during the COVID-19 years, demonstrating significant reductions in hospitalization and death in higher-risk persons, as well as the time to viral elimination. However, it does not shorten the duration of symptoms, and there is little evidence that Paxlovid reduces the risk of developing long COVID symptoms.
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