Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity.

To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.

Déclaration de conflit d'intérêts

I have read the journal’s policy and the authors of this manuscript have the following competing interests: HP reports personal fees from MSD, Janssen, and Biomerieux. ET reports research grants from Servier and Vaxeal; reports honorarium fees from BMS and Merck-MSD; reports honorarium fees for participation on advisory boards from BMS and Astra-Zeneca. PLT reports honorarium fees for participation on advisory boards for Retrophin Inc not related to this work. JBA reports consultancy/expert testimony and honoraria from Novartis and Pfizer. BC reports receiving consulting fees and honoraria for lectures at symposia from Edwards Life Sciences, Orion Pharma, Amomed, and Nordic Pharma. MZ reports research grants from the French Ministry of Health, Quantum Genomics, and the European Horizon 2020 program; reports grant support and nonfinancial support from ReCor Medical and Idorsia; and reports personal fees from CVRx. JSH reports grants from Bioserenity, Sanofi, Servier and Novo Nordisk. J.S.H; reports speaker, advisory board or consultancy fees from Amgen, Astra Zeneca, Bayer, Bristol-Myers Squibb, Novartis, Novo Nordisk. SC reports personal fees from Novonordisk, Lilly, Kabi, Janssen-Cilag, Servier, outside the submitted work; reports other from MyGoodLife. FP reported receiving grants from Bristol-Myers and Squibb and HalioDx outside the submitted work; participation in Scientific Advisory Boards & Meetings for Bristol-Myers Squibb, Roche, Janssen, Merck, and Gilead. DMS received consulting fees or travels expenses from Boehringer Ingelheim, Léo Pharma, Aspen and Carmat. None of them are related to the work described here. M-ADD reported having received speaker fees from BMS, Gilead and Roche outside the submitted work. The remaining authors declared no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.