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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.

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