biomarkers for dexamethasone response in sars-cov-2 / covid-19 pneumonia

Conditions: Pneumonia, Viral; SARS-Cov-2

Summary: the primary objective of this study is to demonstrate (at the time of admission) biomarkers of interest (human plasma bak125 panel + interferon panel) for dexamethasone responders versus non-responders in sars-cov-2 hypoxemic pneumonia. the secondary objectives are to describe and compare between groups: * the number of days without mechanical ventilation * the need for mechanical ventilation * 28-day mortality * progression towards acute respiratory distress syndrome (ards) * change in the qsofa score * length of hospitalization * the change in the extent of lesions on thoracic computed tomography scan between inclusion and d7 (or the day of discharge from hospital if \<d7) * change in biomarkers on d0, d2, d4, d7 (nfs, liver tests (asat, alat), creatinine, albumin, crp, d-dimers, ferritin, ldh, lymphocyte phenotyping) * demonstrate other biomarkers of interest from the usual management (nfs, liver function tests (asat, alat), creatinine, albumin, crp, d-dimers, ferritin, ldh, lymphocyte phenotyping) * change in biomarkers evaluated by mass spectrometry (on a blood sample) on d0 and d7 +/- 2 days * the initial viral load (within 48 hours preceding d0) and at d7 of inclusion estimated from the nasopharyngeal sars-cov-2 rt-pcr * initial sars-cov-2 serology and on d7 from inclusion * the a38g polymorphism of the gene coding for club cell secretory protein (ccsp) for each patient * short-term complications related to corticosteroid therapy * the quantitative and qualitative impact of corticosteroid therapy on lymphocytes from patients with covid-19.

this is a prospective multicenter cohort of patients treated with the usual standard of care including systemic corticosteroid therapy with dexamethasone 6 mg / day. inclusion (d0): the patients are examined on the day of their hospital admission. after an initial eligibility check and if interest is expressed by the patient, a specific inclusion visit is carried out. follow-up: patients are clinically evaluated at least twice a day (clinical examination, spo2, vital signs) during hospitalization. chest computed tomography and sars-cov-2 serology are performed on d0. viral load is evaluated by the polymerase chain reaction which allowed the diagnosis of covid-19 in the 48 hours preceding d0 and on d7. the evaluation of conventional biomarkers of interest (blood count, hepatic assessment (asat, alat), serum creatinine, albuminemia, crp, d-dimers, ldh, ferritin) are carried out on d0 (before the 1st dose of corticosteroids), d2 , j4 and j7. the evaluation of biomarkers of interest evaluated by mass spectrometry is carried out on d0 and d7 +/- 2 days. a follow-up call on d28 is carried out (telephone call, collection of vital status and hospitalizations).

Eligibility criteria:
inclusion criteria: * hospitalization for sars-cov-2 pneumonia * sars-cov-2 infection proven by polymerase chain reaction (nasopharyngeal or other respiratory sampling (expectoration, tracheal aspiration, bronchoalveolar lavage fluid) * presence of at least one of the following clinical signs of infectious pneumonia: fever (\>38°c), cough, dyspnoea, thoracic pain, crackling/rales * presence of at least one of the following on a lung computed tomography scan performed within two days of inclusion/randomisation: uni- or bilateral ground glass opacities, consolidations, alveolar condensations, inter- or intra-lobular reticulations, crazy paving * indication for dexamethasone corticotherapy (defined by the presence of hypoxemia with room-air spo2 \ 94%) exclusion criteria: * systemic long-term anti-inflammatory treatment (corticosteroids or anti-interleukins) for chronic disease * systemic corticosteroid treatment in the 15 days preceding the eligibility visit (for disease other than covid-19) * systemic corticosteroid treatment for covid-19 started more than 48h before the eligibility visit * absolute contraindication for systemic corticosteroid treatment * aside from the current acute episode, life expectancy of \<6 months * patient unable to comply with all study procedures (e.g. contraindication for thoracic scans or bloodwork) * protected populations according to the french public health code (pregnant, parturient or lactating women; adults under any form of guardianship; prisoners or persons under any form of judicial protection) * potential interference from other studies (participation in any clinical trial of an investigational agent or procedure within one month prior to screening or during the study; exclusion period determined by another study.) * it is impossible to correctly inform the patient (e.g. language barrier) * absence of free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research) * non-beneficiary of the french social security, single-payer health insurance system

Keywords: hypoxemic pneumonia corticosteroid glucocorticosteroid systemic corticosteroid covid-19