Use of Paxlovid for Treatment of Acute COVID-19 and Occurrence of Post-COVID Conditions among Children and Adults at High-Risk for Severe COVID-19, April 1 - December 31, 2022

Dalton et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofad500.2468

Oct 2023

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Retrospective 874,299 COVID-19 patients in the USA, showing lower risk of post-COVID conditions for patients 50+, no significant difference for ages 18-49, and higher risk for age 12-17.

Resistance. Variants may be resistant to paxlovid1-4. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID5.

Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid6. 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"7.

AKI. Kamo et al. show significantly increased risk of acute kidney injury.

Standard of Care (SOC): SOC for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments9. Only expensive, high-profit treatments were approved. Low-cost treatments were excluded, reducing the probability of treatment—especially early—due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.

Important missing comments or errors? Let us know.

risk of PASC, 8.0% lower, RR 0.92, p < 0.001, 50+, 1+ PCC, propensity score matching.

risk of PASC, 1.0% higher, RR 1.01, p = 0.33, 18-49, 1+ PCC, propensity score matching.

risk of PASC, 7.0% higher, RR 1.07, p = 0.005, 12-17, 1+ PCC, propensity score matching.

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

1. Zhou et al., Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system, Science Advances, doi:10.1126/sciadv.add7197.science.org, doi.org.

2. Jochmans et al., The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir, mBio, doi:10.1128/mbio.02815-22.asm.org, doi.org.

3. Lopez et al., SARS-CoV-2 Resistance to Small Molecule Inhibitors, Current Clinical Microbiology Reports, doi:10.1007/s40588-024-00229-6.springer.com, doi.org.

4. Zvornicanin et al., Molecular Mechanisms of Drug Resistance and Compensation in SARS-CoV-2 Main Protease: The Interplay Between E166 and L50, bioRxiv, doi:10.1101/2025.01.24.634813.biorxiv.org, doi.org.

5. Thomas et al., Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator, bioRxiv, doi:10.1101/2024.10.18.619137.biorxiv.org, doi.org.

6. Hoertel et al., Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease, JAMA Network Open, doi:10.1001/jamanetworkopen.2022.42140.jamanetwork.com, doi.org.

7. FDA, Fact sheet for healthcare providers: emergency use authorization for paxlovid, www.fda.gov/media/155050/download.fda.gov.

8. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

9. c19early.org, c19early.org/soc/usa.html.c19early.org/soc/usa.html.

Dalton et al., 11 Oct 2023, retrospective, USA, preprint, 8 authors, study period 1 April, 2022 - 31 December, 2022.

This Paper Paxlovid All

Abstract: Abstract citation ID: ofad500.2468 1937. Use of Paxlovid for Treatment of Acute COVID-19 and Occurrence of Post-COVID Conditions among Children and Adults at High-Risk for Severe COVID-19, April 1 - December 31, 2022 Alexandra F. Dalton, PhD1; Sarah Baca, B.Sc. Environmental Science, B.Sc. Mathematics2; Julia Raykin, PhD3; Cria Perrine, PhD3; Tegan Boehmer, PhD, MPH1; Emilia Koumans, MD, MPH3; Priti Patel, MD, MPH1; Sharon Saydah, PhD1; 1Centers for Disease Control and Prevention, Raleigh, NC; 2GAP Solutions Inc., Austin, Texas; 3CDC, Atlanta, Georgia Session: 176. Late Breaking Abstracts: COVID-19 & Friends Friday, October 13, 2023: 2:21 PM Figure 1. Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages ≥50 (N=564,303) Figure 2. Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 18-49 (N=292,818) Figure 3. Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 12-17 (N=17,178) Late Breaking Abstracts • OFID 2023:10 (Suppl 2) • S1269 Background. Data have suggested that treatment with Paxlovid for acute COVID-19 decreases the incidence of Post-COVID Conditions (PCC); however, results are limited to speciﬁc age groups and populations. This analysis assessed the occurrence of PCC following receipt of Paxlovid among children and adults at risk for severe COVID-19. Methods. Patients aged ≥ 12 years with COVID-19 (deﬁned by ICD-10 code, positive SARS-CoV-2 test, or Paxlovid prescription) and at increased risk for severe COVID-19 due to age, underlying conditions, or immune-suppressing medications, were identiﬁed in HealthVerity claims data. Eligible persons had an outpatient, telehealth, or emergency department encounter for COVID-19 between April 1 – August 31, 2022. Exclusions included liver disease, end-stage renal disease, a prescription for contraindicated medications, pregnancy in the previous year, or death within 60 days. Case patients received a Paxlovid prescription within ±5 days of the index date; control patients matched on age, sex, month, and region did not receive Paxlovid within ±5 days. Cases and controls were matched 1:2. Analysis was conducted separately for 3 age groups: 12-17 years, 18-49 years, and ≥50 years. PCC was deﬁned as new conditions > 60 days after index date and prior to December 31, 2022. We calculated the relative risk (RR) of two overall PCC indicators (≥ 1 or ≥ 2 conditions) and 45 individual conditions. Results. Among adults aged ≥ 50 years, the risks of overall and individual PCCs were generally lower among case- than control patients (RR for ≥1 condition=0.92, 95% CI=0.91-0.93; Figure 1). There was no overall difference in risk among adults 18-49; the RR of individual conditions varied (Figure 2). Among adolescents, the risks of overall and individual PCCs were higher among case than control patients (RR for ≥1 condition=1.07, 95% CI=1.02-1.12; Figure 3). Conclusion. The results suggest that Paxlovid helps reduce occurrence of PCC in adults aged ≥ 50 years. Among younger adults and adolescents, associations were observed for only certain conditions. This may be due to a difference in baseline health in these age groups. Further investigation may help clarify whether Paxlovid provides beneﬁts in reducing PCC in addition to severity of acute COVID-19. Disclosures. Priti Patel, MD, MPH, Pﬁzer:..

DOI record: { "DOI": "10.1093/ofid/ofad500.2468", "ISSN": [ "2328-8957" ], "URL": "http://dx.doi.org/10.1093/ofid/ofad500.2468", "abstract": "Abstract\n \n Background\n Data have suggested that treatment with Paxlovid for acute COVID-19 decreases the incidence of Post-COVID Conditions (PCC); however, results are limited to specific age groups and populations. This analysis assessed the occurrence of PCC following receipt of Paxlovid among children and adults at risk for severe COVID-19.\n \n \n Methods\n Patients aged ≥ 12 years with COVID-19 (defined by ICD-10 code, positive SARS-CoV-2 test, or Paxlovid prescription) and at increased risk for severe COVID-19 due to age, underlying conditions, or immune-suppressing medications, were identified in HealthVerity claims data. Eligible persons had an outpatient, telehealth, or emergency department encounter for COVID-19 between April 1 – August 31, 2022. Exclusions included liver disease, end-stage renal disease, a prescription for contraindicated medications, pregnancy in the previous year, or death within 60 days. Case patients received a Paxlovid prescription within ±5 days of the index date; control patients matched on age, sex, month, and region did not receive Paxlovid within ±5 days. Cases and controls were matched 1:2. Analysis was conducted separately for 3 age groups: 12-17 years, 18-49 years, and ≥50 years. PCC was defined as new conditions &gt; 60 days after index date and prior to December 31, 2022. We calculated the relative risk (RR) of two overall PCC indicators (≥ 1 or ≥ 2 conditions) and 45 individual conditions.\n \n \n Results\n Among adults aged ≥ 50 years, the risks of overall and individual PCCs were generally lower among case- than control patients (RR for ≥1 condition=0.92, 95% CI=0.91-0.93; Figure 1). There was no overall difference in risk among adults 18-49; the RR of individual conditions varied (Figure 2). Among adolescents, the risks of overall and individual PCCs were higher among case than control patients (RR for ≥1 condition=1.07, 95% CI=1.02-1.12; Figure 3).Figure 1.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages ≥50 (N=564,303)Figure 2.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 18-49 (N=292,818)Figure 3.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 12-17 (N=17,178)\n \n \n Conclusion\n The results suggest that Paxlovid helps reduce occurrence of PCC in adults aged ≥ 50 years. Among younger adults and adolescents, associations were observed for only certain conditions. This may be due to a difference in baseline health in these age groups. Further investigation may help clarify whether Paxlovid provides benefits in reducing PCC in addition to severity of acute COVID-19.\n \n \n Disclosures\n Priti Patel, MD, MPH, Pfizer: Stocks/Bonds\n ", "author": [ { "affiliation": [ { "name": "Centers for Disease Control and Prevention , Raleigh, NC" } ], "family": "Dalton", "given": "Alexandra F", "sequence": "first" }, { "affiliation": [ { "name": "GAP Solutions Inc. , Austin, Texas" } ], "family": "Baca", "given": "Sarah", "sequence": "additional" }, { "affiliation": [ { "name": "CDC , Atlanta , Georgia" } ], "family": "Raykin", "given": "Julia", "sequence": "additional" }, { "affiliation": [ { "name": "CDC , Atlanta , Georgia" } ], "family": "Perrine", "given": "Cria", "sequence": "additional" }, { "affiliation": [ { "name": "Centers for Disease Control and Prevention , Raleigh, NC" } ], "family": "Boehmer", "given": "Tegan", "sequence": "additional" }, { "affiliation": [ { "name": "CDC , Atlanta , Georgia" } ], "family": "Koumans", "given": "Emilia", "sequence": "additional" }, { "affiliation": [ { "name": "Centers for Disease Control and Prevention , Raleigh, NC" } ], "family": "Patel", "given": "Priti", "sequence": "additional" }, { "affiliation": [ { "name": "Centers for Disease Control and Prevention , Raleigh, NC" } ], "family": "Saydah", "given": "Sharon", "sequence": "additional" } ], "container-title": "Open Forum Infectious Diseases", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 11, 27 ] ], "date-time": "2023-11-27T02:17:17Z", "timestamp": 1701051437000 }, "deposited": { "date-parts": [ [ 2023, 11, 27 ] ], "date-time": "2023-11-27T02:17:18Z", "timestamp": 1701051438000 }, "indexed": { "date-parts": [ [ 2023, 11, 27 ] ], "date-time": "2023-11-27T05:18:30Z", "timestamp": 1701062310032 }, "is-referenced-by-count": 0, "issue": "Supplement_2", "issued": { "date-parts": [ [ 2023, 11, 27 ] ] }, "journal-issue": { "issue": "Supplement_2", "published-print": { "date-parts": [ [ 2023, 11, 27 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 11, 27 ] ], "date-time": "2023-11-27T00:00:00Z", "timestamp": 1701043200000 } } ], "link": [ { "URL": "https://academic.oup.com/ofid/article-pdf/10/Supplement_2/ofad500.2468/53773788/ofad500.2468.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "syndication" }, { "URL": "https://academic.oup.com/ofid/article-pdf/10/Supplement_2/ofad500.2468/53773788/ofad500.2468.pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "286", "original-title": [], "prefix": "10.1093", "published": { "date-parts": [ [ 2023, 11, 27 ] ] }, "published-online": { "date-parts": [ [ 2023, 11, 27 ] ] }, "published-other": { "date-parts": [ [ 2023, 12 ] ] }, "published-print": { "date-parts": [ [ 2023, 11, 27 ] ] }, "publisher": "Oxford University Press (OUP)", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofad500.2468/7448238" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "1937. Use of Paxlovid for Treatment of Acute COVID-19 and Occurrence of Post-COVID Conditions among Children and Adults at High-Risk for Severe COVID-19, April 1 - December 31, 2022", "type": "journal-article", "volume": "10" }

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