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0 0.5 1 1.5 2+ PASC, 30-180, broad 20% Improvement Relative Risk PASC, 30-180, narrow 25% PASC, 90-180, broad 29% PASC, 90-180, narrow 26% Paxlovid for COVID-19  Patel et al.  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? PSM retrospective 2,008 patients in the USA (Dec 2021 - Apr 2022) Lower PASC with paxlovid (p=0.014) Patel et al., medRxiv, April 2023 Favors paxlovid Favors control

Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir

Patel et al., medRxiv, doi:10.1101/2023.04.05.23288196
Apr 2023  
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TriNetX retrospective 1,004 paxlovid patients and matched controls, showing lower risk of PASC with treatment.
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, (B), vitamin D (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. 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.
risk of PASC, 20.0% lower, RR 0.80, p = 0.01, treatment 1,004, control 1,004, broadly defined, 30-180 days, propensity score matching.
risk of PASC, 25.0% lower, RR 0.75, p = 0.01, treatment 1,004, control 1,004, narrowly defined, 30-180 days, propensity score matching.
risk of PASC, 29.0% lower, RR 0.71, p = 0.01, treatment 1,004, control 1,004, broadly defined, 90-180 days, propensity score matching.
risk of PASC, 26.0% lower, RR 0.74, p = 0.01, treatment 1,004, control 1,004, narrowly defined, 90-180 days, propensity score matching.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Patel et al., 6 Apr 2023, retrospective, USA, preprint, mean age 57.2, 17 authors, study period 1 December, 2021 - 17 April, 2022. Contact:
This PaperPaxlovidAll
Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir 
MD Rushin Patel, MD Sourbha S Dani, MD Sumanth Khadke, MD Javaria Ahmad, MD Jui Shah, MD MPH Neev Mehta, MD Kenneth Wener, MD Daniel P Mcquillen, MD MPH George Abraham, MD Jeremy Faust, MD Jason Maley, MD Smita Patel, MD Janet Mullington, MD Robert M Wachter, MD Anne Mosenthal, MD Paul E Sax, MD Sarju Ganatra
Assessment of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC), based on broad and narrow definitions in non-hospitalized, vaccinated patients between 30-180 days and 90-180 days.
Al-Aly, Bowe, Xie, Long COVID after breakthrough SARS-CoV-2 infection, Nat Med
Antonelli, Pujol, Spector, Ourselin, Steves, Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2, Lancet
Bernal, Da Silva, Musungaie, Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med
Cdc, Long COVID or Post-COVID Conditions
Elfein, Number of coronavirus (COVID-19) cases, recoveries, and deaths worldwide
Fad, FDA Authorizes New Monoclonal Antibody for Treatment of COVID-19 that Retains Activity Against Omicron Variant
Ganatra, Dani, Ahmad, Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019 (COVID-19), Clinical Infectious Diseases
Gottlieb, Vaca, Paredes, Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients, N Engl J Med
Hammond, Leister-Tebbe, Gardner, Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med
Organization, Post COVID-19 condition (Long COVID
Rando, Bennett, Byrd, Challenges in defining Long COVID: Striking differences across literature, Electronic Health Records, and patient-reported information, medRxiv
Recover, Explore Research
Rio, Collins, Malani, Long-term Health Consequences of COVID-19, JAMA
Swank, Senussi, Manickas-Hill, Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae, Clin Infect Dis
Trinetx, The global health research network
University, Paxlovid for Treatment of Long Covid
Uo, COVID-OUT: Early Outpatient Treatment for SARS-CoV-2 Infection (COVID-19
Xie, Choi, Al-Aly, Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19, medRxiv
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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