In this regard, the present research project aims to compare dexamethasone PK in normal-weight versus obese patients treated for COVID-19.

This observational study will include patients hospitalized at HUG (Division of General Internal Medicine) with COVID-19 and treated with oral DEX. This study will include 2 groups of patients according to their body mass index (BMI) (normal weight with a BMI of 18.5-25.0 kg/m2; obese/ morbidly obese with a BMI ≥30). The primary outcome will be the assessment of the differential impact of weight on DEX PK. Finally, the data generated will be used to build a physiologically based PK (PBPK) model for DEX and in different sub-groups. The model will aim to predict the effect of BMI in virtual populations with different drugs and in different scenarios. This should allow prospective dose adjustment of DEX based on patient weight.

Before starting the study, COVID-19 patients receiving dexamethasone as part of their hospital management and meeting the criteria of inclusion and non-exclusion will have an information session with an investigator as described above.

During the study session, capillary blood samples will be taken during a total of 8 hours, time starting just before DEX administration, and at the following times after the dose: time of the drug intake, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours. The capillary blood sample will be obtained by pricking the fingertip using contact-activated lancet (BD Microtainer). A total of five blood drops (10 μL each) will be collected by a micropipette and will be dropped off on the blotting paper 903 S&S (Whatman). After a 45-minute drying time at room temperature, dried blood samples (DBS) samples will be packed in sealable plastic bags containing a desiccant and stored at - 80°C until analysis. Drugs will be extracted from DBS using methanol. DEX quantification in capillary DBS will be performed using reverse-phase- HPLC coupled to tandem mass spectrometer (MS/MS). In addition to this, an EDTA tube (3 ml) of blood will be collected and preserved in the biobank (-80°C) and will be used whether further analysis should be performed on the samples. In this aim an authorization to reuse the samples will be requested from each patient during the consent signature.

Inclusion Criteria:

• Male and female patients ≥ 18 years receiving DEX for COVID-19
• Stable dose of DEX for at least 24 hours
• BMI between 18.5 and 25 or ≥ 30 kg/m2
• Understanding of French orEnglish languages and ability to give a written inform consent

Exclusion Criteria:

• Medical history of cirrhosis (Child Pugh B and C) or/and nonalcoholic fatty liver disease.
• History of bariatric or other gastric surgery that may affect the drug absorption
• Patient already included in a clinical trial of an investigational drug
• Use of drugs that may affect CYP3A activity * *based on the 'drug interactions and cytochromes P450' table published by The Division of clinical Pharmacology and Toxicology [15], HUG and on the investigator's knowledge and on the drug interactions website from the University of Liverpool (https://www.covid19- druginteractions.org/checker).

Thirty COVID-19 hospitalized patients will be informed and included in the study after giving a written informed consent. The control group will include mainly normal weight patients (BMI 18.5- 25 kg/m2) receiving DEX.