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Scientific article
Open access
English

Impact of SARS-CoV-2 Infection (COVID-19) on Cytochromes P450 Activity Assessed by the Geneva Cocktail

Published inClinical pharmacology and therapeutics, vol. 110, no. 5, p. 1358-1367
Publication date2021-11
First online date2021-09-21
Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a severe acute respiratory syndrome with an underlying inflammatory state. We have previously demonstrated that acute inflammation modulates cytochromes P450 (CYPs) activity in an isoform-specific manner. We therefore hypothesized that COVID-19 might also impact CYP activity, and thus aimed to evaluate the impact of acute inflammation in the context of SARS-CoV-2 infection on the six main human CYPs activity. This prospective observational study was conducted in 28 patients hospitalized at the Geneva University Hospitals (Switzerland) with a diagnosis of moderate to severe COVID-19. They received the Geneva phenotyping cocktail orally during the first 72 hours of hospitalization and after 3 months. Capillary blood samples were collected 2 hours after cocktail administration to assess the metabolic ratios (MRs) of CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were also measured in blood. CYP1A2, CYP2C19, and CYP3A MRs decreased by 52.6% (P = 0.0001), 74.7% (P = 0.0006), and 22.8% (P = 0.045), respectively, in patients with COVID-19. CYP2B6 and CYP2C9 MRs increased by 101.1% (P = 0.009) and 55.8% (P = 0.0006), respectively. CYP2D6 MR variation did not reach statistical significance (P = 0.072). As expected, COVID-19 was a good acute inflammation model as mean serum levels of CRP, IL-6, and TNF-α were significantly (P < 0.001) higher during SARS-CoV-2 infection. CYP activity are modulated in an isoform-specific manner by SARS-CoV-2 infection. The pharmacokinetics of CYP substrates, whether used to treat the disease or as the usual treatment of patients, could be therefore clinically impacted.

eng
Keywords
  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / metabolism
  • COVID-19 / blood
  • COVID-19 / enzymology
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Genetic Variation
  • Humans
  • Interleukin-6 / blood
  • Linear Models
  • Male
  • Middle Aged
  • Models, Theoretical
  • Prospective Studies
  • Tumor Necrosis Factor-alpha / blood
Funding
  • Geneva University Hospitals (HUG) - [PRD 5-2018-I]
Citation (ISO format)
LENOIR, Camille et al. Impact of SARS-CoV-2 Infection (COVID-19) on Cytochromes P450 Activity Assessed by the Geneva Cocktail. In: Clinical pharmacology and therapeutics, 2021, vol. 110, n° 5, p. 1358–1367. doi: 10.1002/cpt.2412
Main files (1)
Article (Published version)
Secondary files (4)
Identifiers
ISSN of the journal0009-9236
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Technical informations

Creation02/16/2022 3:25:00 PM
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