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Evolving COVID-19 Landscape: Assessing the Effectiveness and Safety Profile of Nirmatrelvir/Ritonavir in Adolescents

Lee et al., Pediatric Infectious Disease Journal, doi:10.1097/INF.0000000000004594
Nov 2024  
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Mortality -813% Improvement Relative Risk Progression, ED visit -360% Progression, return visit 8% Paxlovid for COVID-19  Lee et al.  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? Retrospective 374 patients in the USA (January 2022 - July 2023) Higher mortality (p=0.06) and progression (p=0.098), not sig. c19early.org Lee et al., Pediatric Infectious Disea.., Nov 2024 Favorspaxlovid Favorscontrol 0 0.5 1 1.5 2+
Retrospective 374 adolescent COVID-19 outpatients showing no significant differences with paxlovid treatment.
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.
risk of death, 813.0% higher, RR 9.13, p = 0.06, treatment 2 of 92 (2.2%), control 0 of 282 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of progression, 359.8% higher, RR 4.60, p = 0.10, treatment 3 of 92 (3.3%), control 2 of 282 (0.7%), emergency department visit.
risk of progression, 8.0% lower, RR 0.92, p = 1.00, treatment 3 of 92 (3.3%), control 10 of 282 (3.5%), NNT 351, COVID-19-related hospital admission, emergency department visit, or outpatient visit.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Lee et al., 14 Nov 2024, retrospective, USA, peer-reviewed, 3 authors, study period 1 January, 2022 - 31 July, 2023. Contact: phle@montefiore.org.
This PaperPaxlovidAll
Evolving COVID-19 Landscape: Assessing the Effectiveness and Safety Profile of Nirmatrelvir/Ritonavir in Adolescents
PharmD Philip Lee, Kiriam Escobar Lee, MD, MPH Brenda I Anosike
Pediatric Infectious Disease Journal, doi:10.1097/inf.0000000000004594
This study evaluates nirmatrelvir/ritonavir (Paxlovid) in preventing severe coronavirus disease 2019 in adolescents (12-18). Conducted from January 2022 to July 2023, it compared hospital admissions and healthcare visits within 30 days post-treatment. Results showed similar follow-up rates between treated and untreated groups, with slightly more adverse effects in the nirmatrelvir/ritonavir group. Further research is needed to confirm its efficacy in this population.
References
Bahl, Mielke, Johnson, Severe COVID-19 outcomes in pediatrics: an observational cohort analysis comparing Alpha, Delta, and Omicron variants, Lancet Reg Health Am
Bose-Brill, Hirabayashi, Pajor, Pediatric nirmatrelvir/ritonavir prescribing patterns during the COVID-19 pandemic, medRxiv
Brown, Moore, Hooper, Interventions for preventing obesity in children, Cochrane Database Syst Rev
Choi, Choi, Yun, Risk factors for severe COVID-19 in children: a systematic review and meta-analysis, J Korean Med Sci
Costagliola, Spada, Consolini, Age-related differences in the immune response could contribute to determine the spectrum of severity of COVID-19, Immun Inflamm Dis
Esposito, Autore, Argentiero, Update on COVID-19 therapy in pediatric age, Pharmaceuticals
Fernandez, Perez, Hernandez, Factors and mechanisms for pharmacokinetic differences between pediatric population and adults, Pharmaceutics
Graff, Smith, Silveira, Risk factors for severe COVID-19 in children, Pediatr Infect Dis J
Hammond, Leister-Tebbe, Gardner, Oral nirmatrelvir for highrisk, nonhospitalized adults with Covid-19, N Engl J Med
Hoering, Leblanc, Crowley, Seamless phase I-II trial design for assessing toxicity and efficacy for targeted agents, Clin Cancer Res
Iuliano, Brunkard, Boehmer, Trends in disease severity and health care utilization during the early Omicron variant period compared with previous SARS-CoV-2 high transmission periods-United States, December 2020-January 2022, MMWR Morb Mortal Wkly Rep
Jabakhanji, Boland, Ward, Body mass index changes in early childhood, J Pediatr
Levin, Whittaker, Balancing risk and benefit of SARS-CoV-2 vaccines in children, Lancet Reg Health Eur
Lu, Rosenbaum, Developmental pharmacokinetics in pediatric populations, J Pediatr Pharmacol Ther
Rotulo, Palma, Understanding COVID-19 in children: immune determinants and post-infection conditions, Pediatr Res
Saravolatz, Depcinski, Sharma, Molnupiravir and nirmatrelvir-ritonavir: oral coronavirus disease 2019 antiviral drugs, Clin Infect Dis
Taylor, Whitaker, Anglin, COVID-19-associated hospitalizations among adults during SARS-CoV-2 delta and omicron variant predominance, by race/ethnicity and vaccination status-COVID-NET, 14 states, July 2021, Morb Mortal Wkly Rep
Woodruff, Campbell, Taylor, Risk factors for severe COVID-19 in children, Pediatrics
Yaffe, Pharmacokinetics and pharmacodynamics in children versus adults
Yan, Zhou, Zhu, The feasibility, safety, and efficacy of Paxlovid treatment in SARS-CoV-2-infected children aged 6-14 years: a cohort study, Ann Transl Med
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