key: cord-0941031-d7v94vcw authors: Blanchard, Claire; Perennec, Tanguy; Smati, Sarra; Tramunt, Blandine; Guyomarch, Béatrice; Bigot‐Corbel, Edith; Bordier, Lyse; Borot, Sophie; Bourron, Olivier; Caussy, Cyrielle; Coffin‐Boutreux, Christine; Dutour, Anne; Germain, Natacha; Gonfroy‐Leymarie, Céline; Meyer, Laurent; Prevost, Gaëtan; Roussel, Ronan; Seret‐Bégué, Dominique; Thivolet, Charles; Vergès, Bruno; Pichelin, Matthieu; Gourdy, Pierre; Hadjadj, Samy; Wargny, Matthieu; Pattou, François; Cariou, Bertrand title: History of bariatric surgery and COVID 19 outcomes in patients with type 2 diabetes: results from the CORONADO study date: 2021-09-29 journal: Obesity (Silver Spring) DOI: 10.1002/oby.23314 sha: 0d0b0d6823a98b477dcc1a3c43a5252522532f7e doc_id: 941031 cord_uid: d7v94vcw OBJECTIVE: The objective of this study is to assess the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID‐19. METHODS: Post‐hoc analysis from the nationwide observational CORONADO study: patients with T2D and history of MBS were matched with patients without MBS for age, sex and body mass index (BMI) either at the time of MBS or on admission for COVID‐19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission. RESULTS: Out of 2 398 CORONADO participants, 20 had history of MBS. When matching for BMI at the time of MBS and after adjustment on diabetes duration, the CPO occurred less frequently within 7 days (3 vs 17 events, OR: 0.15 [0.01‐0.94], P=0.03) and 28 days (3 vs 19 events, OR: 0.11 (0.01‐0.71), P=0.02) in patients with MBS (n=16) vs controls (n=44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission. CONCLUSIONS: These data are reassuring regarding COVID‐19 prognosis in patients with diabetes with history of MBS compared to those without MBS. Conclusions These data are reassuring regarding COVID-19 prognosis in patients with diabetes with history of MBS compared to those without MBS. Soon after the beginning of the coronavirus disease-2019 (COVID-19) pandemic, people with obesity were quickly identified as being at risk for severe forms of COVID-19 severity. 1, 2 For instance, we previosuly reported a seven-fold increase in the risk of invasive mechanical ventilation in individuals with a body mass index (BMI) ≥ 35 kg/m 2 admitted with COVID-19 infection compared with those presenting BMI < 25 kg/m 2 . 3 Management of obesity is therefore a priority to reduce the severity of COVID-19. Metabolic and bariatric surgery (MBS) has progressively emerged as the most efficient therapeutic option for patients with severe obesity. 4 Since MBS significantly reduces body weight and improves metabolic comorbidities, 5 one can hypothetize that MBS may decrease the risk of severe COVID-19. Conversely, one cannot exclude that MBS can also lead to undernutrition which could increase the severity of COVID-19. 6 In order to further decipher the relationship between MBS and COVID-19-related outcomes, we conducted a post hoc analysis focused on CORONADO (Coronavirus SARS-CoV2 and Diabetes Outcomes) participants with history of MBS. 7 This article is protected by copyright. All rights reserved The French multicenter nationwide CORONADO study (ClinicalTrials.gov NCT04324736) is a retrospective study designed to describe the phenotypic characteristics and prognosis of patients with diabetes admitted for COVID-19 to 68 French hospitals between March 10 and April 10, The design of the study has been previously reported elsewhere. 7 In this ancillary study, individuals with type 1 diabetes or other causes of diabetes (including newly diagnosed diabetes) were excluded ( Figure S1 ). All patients with personal history of MBS were included in the "exposed" group. These patients were matched 3:1 with other CORONADO participants without history of MBS, according to sex, age (± 3 years) and BMI (± 3 kg/m²) measured either before surgery (exposed/controls, Study A) or at the time of hospital admission (exposed/controls, Study B). In the "control" group, BMI on admission was used to match both groups. The percentage of excess weight loss (%EWL) was defined as: (weight loss / baseline excess weight) × 100. The success of MBS was defined as EWL ≥ 50%. The composite primary outcome (CPO) combined invasive mechanical ventilation (IMV) and/or death by day 7 (D7). A secondary time point was considered by day 28 (D28) for all patients alive and not discharged by D7 in order to consider outcomes between admission and D28. Quantitative variables are expressed using mean ± standard deviation (SD) or median [25 th -75 th percentile] and categorical variables using number (%). The statistical association between two categorical variables was tested using Fisher's exact test. The statistical association between binary and quantitative variables was tested using unpaired t-test (Mann-Whitney U test in case of skewed distribution) and, for variables with more than two categories, we used ANOVA (Kruskal-Wallis in case of skewed distribution). Confidence intervals for proportions were calculated using the Clopper-Pearson estimate. This article is protected by copyright. All rights reserved Logistic regression models were used to calculate odds ratio (OR) associated with the different outcomes by D7. For quantitative variables, OR were expressed for an increase of 1 SD. Multiple logistic regression analyses were performed focusing on the OR associated with BMI, considering covariates identified either as clinically relevant (background knowledge) and/or significantly associated with obesity status in univariable analysis. All statistical tests were two-sided with a type 1 error set at 5%, without correction for multiple testing. All analyses were performed on available data, without imputation, using statistical software R version 4.0.0. This article is protected by copyright. All rights reserved Among 2 398 participants with T2D in the CORONADO study, 20 (0.83%) had a previous history of MBS, performed a median of 8.5 years (0 to 19 years) before hospital admission. The main clinical characteristics of patients with or without a history of MBS on admission are shown in Table S1 . Patients with a history of MBS patients were mostly female (60%) with a mean age of 59.0 ± 10.8 years. Sixteen patients (80%) underwent a single procedure: 5 gastric banding (GB), 5 sleeve gastrectomies (SG) and 6 Roux-en-Y gastric bypasses (RYGB), while 2 patients underwent respectively 2 or 3 procedures. The success of MBS defined by an EWL ≥ 50% was observed in 8 patients (4 RYGB, 2 GB and 2SG), while 7 patients had a failure (3 GB, 1 SG, 2 RYGB). The EWL could not be calculated in 5 patients due to missing data. By D7 following admission, 5 out of 20 patients with MBS (25%) experienced the primary composite outcome -mainly invasive mechanical ventilation (4 patients, 20%) rather than death (1 patient, 5%). By D28, one additional patient died. When compared with all patients with T2D Since preoperative BMI was lacking in 4 patients, this analysis included 16 out of 20 patients (80%) with history of MBS. Their clinical characteristics are detailed in Table 1 . Patients with obesity who underwent previous MBS had lower BMI on admission than controls, confirming the persistent effectiveness of MBS on body weight loss. When considering the occurrence of the CPO by D7 or D28, patients with history of MBS were intubated and/or died less frequently than matched patients with T2D without history of MBS (Table 2A) . After further adjustment for diabetes duration, the CPO occurred significantly less frequently in patients with history of MBS by D7 (p= 0.03) and D28 (p= 0.02). This article is protected by copyright. All rights reserved Comparison of baseline characteristics and hospital outcomes of patients with history of The second ancillary analysis included all patients (n = 20) with histories of MBS and 58 patients with T2D matched for age, sex, and on-admission BMI (33.1 ± 5.4 vs 33.0 ± 5.1 kg/m 2 ) ( Table 3) . The rates of death and IMV were not statistically different between the two groups within D7 and D28 after admission. The results were similar after further adjustment for diabetes duration (Table 2B ). This article is protected by copyright. All rights reserved In this observational study, we found that a previous history of MBS was associated with a better prognosis in sex-, age-and BMI-matched patients with T2D hospitalized for COVID-19 during the same time period. Even if the underlying mechanisms remain to be fully elucidated, the association of class II/III obesity with the more severe forms of COVID-19 is now well established. 8, 9 A large body of evidence has also shown that T2D is an independent risk factor for SARS-CoV-2 infection and COVID-19 severity. 7 Although observational, the CORONADO study has several strengths. First, while no previous study has specifically analyzed the impact of MBS on COVID-19 outcome in T2D, it should be noted that the proportion of patients with history of previous MBS in our study population (0.8%) was in agreement with the expected proportion of operated patients in people with T2D in France. 16, 17 Second, we showed that participants with a history of previous MBS presented slightly lower HbA 1C and glycemia on admission. This latter finding suggests that MBS is able to counterbalance the burden of diabetic complications on COVID-19 outcomes. 8, 18 Some limitations should be mentioned. The most obvious is the observational design of our study, the low number of patients with MBS, the low number of CPO events (especially regarding deaths) and the absence of randomization between exposed and unexposed patients, which makes the control of confounding factors uncertain. Also, we did not account for multiple testing. Finally, This article is protected by copyright. All rights reserved substantial data were missing, such as preoperative BMI which could not be documented in 4 patients (20%). In conclusion, our study suggested that a previous history of MBS in obese patients with T2D and hospitalized for COVID-19 might be associated with a better prognosis than in those without MBS. Prospective studies are needed to confirm these results in larger populations in order to further promote efficient weight loss interventions as therapeutic strategy to improve COVID-19 prognosis in patients with severe obesity. This article is protected by copyright. All rights reserved Accepted Article Table 2A . COVID-related clinical outcomes in patients with history of metabolic and bariatric surgery (exposed) and age, sex and on admission or preoperative BMI-matched controls (exposed/controls, Study A All patients with personal history of MBS were included in the "exposed" group. These patients were matched 3:1 with other CORONADO participants without history of MBS, according to sex, age (± 3 years) and BMI (± COVID-19 and diabetes mellitus: from pathophysiology to clinical management The impact of obesity on severe disease and mortality in people with SARS-CoV-2: a systematic review and meta-analysis High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation Long-term outcomes of bariatric surgery: a National Institutes of Health symposium Benefits and risk of bariatric surgery in adults: a review Obesity, malnutrition, and trabce element deficiency in the coronavirus disease (COVID-19) pandemic: an overview Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study Relationship between obesity and severe COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study Prevalence of obesity among adult inpatients with COVID-19 in France Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study COVID-19 and its Severity in Bariatric Surgery-Operated Patients The Impact of Previous History of Bariatric Surgery on Outcome of COVID-19. A Nationwide Medico-Administrative French Study Association of prior metabolic and bariatric surgery with severity of coronavirus disease 2019 (COVID-19) in patients with obesity COVID-19 and Obesity: Is Bariatric Surgery Protective? Retrospective Analysis on 2145 Patients Undergone Bariatric-Metabolic Surgery from High Volume Center in Italy (Lombardy) Impact of Centralized Management of Bariatric Surgery Complications on 90-day Mortality Association Between Bariatric Surgery and Rates of Continuation, Discontinuation, or Initiation of Antidiabetes Treatment 6 Years Later Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study We wish to thank the sponsor (DRCI CHU Nantes) Clinical Project Manager (Maëva Saignes) and assistant (Jeanne Saunier), Clinical Research Associates (Selma El Andaloussi, Joëlle Martin-Gauthier, Emily Rebouilleau) and data manager (Tanguy Roman). We thank the Communication Manager of l'Institut du Thorax (Vimla Mayoura). We acknowledge all medical staff involved in the diagnosis and treatment of patients with COVID-19 in participating centers. We thank all GPs, specialists, pharmacists and biological laboratories in charge of hospitalized patients for providing additional medical information to our investigators. We thank the Société Francophone du Diabète (SFD) and Société Française d'Endocrinologie (SFE) for disseminating study design and organization, the Fédération Française des Diabétiques (FFD) for participating in the study organization. This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved Accepted Article