Paxlovid associated with decreased hospitalization rate among adults with COVID-19 — United States, April–September 2022

Shah et al., American Journal of Transplantation, doi:10.1016/j.ajt.2022.12.004, Jan 2023
Hospitalization 51% improvement lower risk ← → higher risk Paxlovid for COVID-19  Shah et al.  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? Retrospective 699,848 patients in the USA Lower hospitalization with paxlovid (p<0.000001) Confounding by health-seeking and additional untracked treatments and measures may substantially overestimate efficacy c19early.org Shah et al., American J. Transplantation, Jan 2023 0 0.5 1 1.5 2+ RR
Retrospective 699,848 outpatients with COVID-19 showing lower hospitalization 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 hygiene1,2, vitamin D3, 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.
Resistance. Variants may be resistant to paxlovid5-12. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID13.
Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid14. 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 paxlovid15.
Kidney and liver injury. Studies show significantly increased risk of acute kidney injury16 and liver injury17.
Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments18. Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
This study is excluded in the after exclusion results of meta analysis: only a fraction of eligible patients received treatment and these patients may be more likely to follow other recommendations, receive additional care, and more more likely to use additional untracked treatments such as vitamin D and nasal/oral hygiene.
Important missing comments or errors? Let us know.
risk of hospitalization, 51.0% lower, HR 0.49, p < 0.001, adjusted per study, multivariable, Cox proportional hazards, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Shah et al., 31 Jan 2023, retrospective, USA, peer-reviewed, 11 authors. Contact: bgn3@cdc.gov.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR USA favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria USA favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Report from the CDC: MMWR Paxlovid associated with decreased hospitalization rate among adults with COVID-19 -United States, April-September 2022
MD Melisa M Shah, Brendan Joyce, MBBS Ian D Plumb, MS Sam Sahakian, PhD Leora R Feldstein, Eric Barkley, MSP Mason Paccione, PhD Joseph Deckert, MPH Danessa Sandmann, MD Jacqueline L Gerhart, MD Melissa Briggs Hagen
doi:10.1016/j.ajt.2022.12.
What is already known about this topic? Nirmatrelvir-ritonavir (Paxlovid) is an outpatient antiviral medication recommended for adults with mild-to-moderate COVID-19 who have elevated risk of severe illness. What is added by this report? Among U.S. adults diagnosed with COVID-19, including those with previous infection or vaccination, persons who were prescribed Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within 30 days after diagnosis than those who were not prescribed Paxlovid. What are the implications for public health practice? Paxlovid should be offered to eligible adults irrespective of vaccination status, especially in groups with the highest risk for severe COVID-19 outcomes, such as older adults and those with multiple underlying health conditions. Nirmatrelvir-ritonavir (Paxlovid), an oral antiviral treatment, is authorized for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness. However, real-world evidence on the benefit of Paxlovid, according to vaccination status, age group, and underlying health conditions, is limited. To examine the benefit of Paxlovid in adults aged !18 years in the United States, a large electronic health record (EHR) data set (Cosmos y ) was analyzed to assess the association between receiving a prescription for Paxlovid and hospitalization with a COVID-19 diagnosis in the ensuing 30 days. A Cox proportional hazards model was used to estimate this association, adjusted for demographic characteristics, geographic location, vaccination, previous infection, and number of underlying health conditions. Among 699,848 adults aged !18 years eligible for Paxlovid during April-August 2022, 28.4% received a Paxlovid prescription within 5 days of COVID-19 diagnosis. Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population (adjusted hazard ratio [aHR] ¼ 0.49), among those who had received !3 mRNA COVID-19 vaccines (aHR ¼ 0.50), and across age groups (18-49 years: aHR ¼ 0.59; 50-64 years: aHR ¼ 0.40; and !65 years: aHR ¼ 0.53). Paxlovid should be prescribed to eligible adults to reduce the risk of COVID-19-associated hospitalization. Paxlovid is an oral antiviral medication that received Emergency Use Authorization by the Food and Drug Administration on December 22, 2021 (1), for use in patients with mild-to-moderate COVID-19 at high risk for progression to severe illness. Eligibility for Paxlovid includes 1) receipt of a positive SARS-CoV-2 test result (including home antigen test), 2) symptoms consistent with mild-to-moderate COVID-19, 3) symptom onset within the past 5 days, 4) age !18 years (or age !12 years and weight !40 kg), 5) one or more risk factors for progression to severe COVID-19, 6) no known or suspected severe renal or hepatic impairment, 7) no history of clinically significant reactions (e.g., toxic epidermal necrolysis or Stevens-Johnson syndrome) to the active ingredients..
References
Arbel, Sagy, Hoshen, Nirmatrelvir use and severe Covid-19 outcomes during the Omicron surge, N Engl J Med, doi:10.1056/NEJMoa2204919
Dryden-Peterson, Kim, Kim, Nirmatrelvir plus ritonavir for early COVID-19 and hospitalization in a large US health system, doi:10.1101/2022.06.14.22276393
Ganatra, Dani, Ahmad, Oral nirmatrelvir and ritonavir in nonhospitalized vaccinated patients with coronavirus disease 2019 (COVID-19), Clin Infect Dis, doi:10.1093/cid/ciac673
Hammond, Leister-Tebbe, Gardner, Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2118542
Lewnard, Malden, Hong, Effectiveness of nirmatrelvir-ritonavir against hospital admission: a matched cohort study in a large US healthcare system, doi:10.1101/2022.10.02.22280623
Najjar-Debbiny, Gronich, Weber, Effectiveness of Paxlovid in reducing severe coronavirus disease 2019 and mortality in high-risk patients, Clin Infect Dis, doi:10.1093/cid/ciac443
Vangeel, Chiu, Jonghe, Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern, Antiviral Res, doi:10.1016/j.antiviral.2022.105252
Wong, Au, Lau, Lau, Cowling et al., Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir among COVID-19 inpatients during Hong Kong's Omicron BA.2 wave: an observational study, Lancet Infect Dis, doi:10.1016/S1473-3099(22)00507-2
Yek, Warner, Wiltz, Risk factors for severe COVID-19 outcomes among persons aged !18 years who completed a primary COVID-19 vaccination series-465 health care facilities, United States, December 2020-October 2021, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm7101a4
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