Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study
Bertrand Cariou, Samy Hadjadj, Matthieu Wargny, Matthieu Pichelin, Abdallah Al-Salameh, Ingrid Allix, Coralie Amadou, Gwénaëlle Arnault, Florence Baudoux, Bernard Bauduceau, Sophie Borot, Muriel Bourgeon-Ghittori, Olivier Bourron, David Boutoille, France Cazenave-Roblot, Claude Chaumeil, Emmanuel Cosson, Sandrine Coudol, Patrice Darmon, Emmanuel Disse, Amélie Ducet-Boiffard, Bénédicte Gaborit, Michael Joubert, Véronique Kerlan, Bruno Laviolle, Lucien Marchand, Laurent Meyer, Louis Potier, Gaëtan Prevost, Jean-Pierre Riveline, René Robert, Pierre-Jean Saulnier, Ariane Sultan, Jean-François Thébaut, Charles Thivolet, Blandine Tramunt, Camille Vatier, Ronan Roussel, Jean-François Gautier, Pierre Gourdy, CORONADO investigators, Bertrand Cariou, Samy Hadjadj, Matthieu Wargny, Matthieu Pichelin, Abdallah Al-Salameh, Ingrid Allix, Coralie Amadou, Gwénaëlle Arnault, Florence Baudoux, Bernard Bauduceau, Sophie Borot, Muriel Bourgeon-Ghittori, Olivier Bourron, David Boutoille, France Cazenave-Roblot, Claude Chaumeil, Emmanuel Cosson, Sandrine Coudol, Patrice Darmon, Emmanuel Disse, Amélie Ducet-Boiffard, Bénédicte Gaborit, Michael Joubert, Véronique Kerlan, Bruno Laviolle, Lucien Marchand, Laurent Meyer, Louis Potier, Gaëtan Prevost, Jean-Pierre Riveline, René Robert, Pierre-Jean Saulnier, Ariane Sultan, Jean-François Thébaut, Charles Thivolet, Blandine Tramunt, Camille Vatier, Ronan Roussel, Jean-François Gautier, Pierre Gourdy, CORONADO investigators
Abstract
Aims/hypothesis: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown.
Methods: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation.
Results: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7.
Conclusions/interpretations: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days.
Trial registration: clinicaltrials.gov NCT04324736.
Keywords: BMI; COVID-19; Death; Diabetes; HbA1c; Hypertension; Mechanical ventilation.
Figures
References
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5.
- Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032.
- Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care. 2003;26(2):510–513. doi: 10.2337/diacare.26.2.510.
- Muller LM, Gorter KJ, Hak E, et al. Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. Clin Infect Dis. 2005;41(3):281–288. doi: 10.1086/431587.
- Yang JK, Feng Y, Yuan MY. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23(6):623–628. doi: 10.1111/j.1464-5491.2006.01861.x.
- Alqahtani FY, Aleanizy FS, Ali El Hadi Mohamed R, et al. Prevalence of comorbidities in cases of Middle East respiratory syndrome coronavirus: a retrospective study. Epidemiol Infect. 2018;147:1–5. doi: 10.1017/S0950268818002923.
- Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–95. doi: 10.1016/j.ijid.2020.03.01.
- Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcome of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA. 2020;323(16):1674–1581. doi: 10.1001/jama.2020.5394.
- Garg S, Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 – COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):458–464. doi: 10.15585/mmwr.mm6915e3.
- Onder G, Rezza G, Brusaferro S (2020) Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 10.1001/jama.2020.4683
- Bhatraju PK, Ghassemieh BJ, Nichols M et al (2020) Covid-19 in critically ill patients in the Seattle region – case series. N Engl J Med. 10.1056/NEJMoa2004500
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)305.
- Wu C, Chen X, Cai Y et al (2020) Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 10.1001/jamainternmed.2020.0994
- Roncon L, Zuin M, Rigatelli G, Zuliani G. Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome. J Clin Virol. 2020;127:104354. doi: 10.1016/j.jcv.2020.104354.
- Centers for Disease Control and Prevention (2020) Coronavirus Disease 2019 (COVID-19): groups at higher risk for severe illness. Available from . Accessed 21 April 2020
- Sauerbrei W, Meier-Hirmer C, Benner A, Royston P. Multivariable regression model building by using fractional polynomials: description of SAS, STATA and R programs. Comput Stat Data Anal. 2006;50(12):3464–3485. doi: 10.1016/j.csda.2005.07.015.
- Pornet C, Bourdel-Marchasson I, Lecomte P, et al. Trends in the quality of care for elderly people with type 2 diabetes: the need for improvements in safety and quality (the 2001 and 2007 ENTRED Surveys) Diabetes Metab. 2011;37(2):152–161. doi: 10.1016/j.diabet.2011.02.001.
- Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475–481. doi: 10.1016/S2213-2600(20)30079-5.
- CDC COVID-19 response team Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019 – United States, February 12–March 28, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(13):382–386. doi: 10.15585/mmwr.mm6913.
- Huang I, Anthonius M, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – a systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395–403. doi: 10.1016/j.dsx.2020.04.018.
- Kulcsar J, Coleman CM, Beck SE, Frieman MD. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI Insight. 2019;4(20):e131774. doi: 10.1172/jci.insight.13177.
- Simonnet A, Chetboun M, Poissy J et al (2020) High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity (Silver Spring). 10.1002/oby.22831
- Schetz M, De Jong A, Deane AM, et al. Obesity in the critically ill: a narrative review. Intensive Care Med. 2019;45(6):757–769. doi: 10.1007/s00134-019-05594-1.
- Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin–angiotensin–aldosterone system inhibitors in patients with COVID-19. N Engl J Med. 2020;382(17):1653–1659. doi: 10.1056/NEJMsr2005760.
- Drucker DJ. Coronavirus infection and type 2 diabetes shared-pathways with therapeutic implications. Endocr Rev. 2020;41(3):bnaa011. doi: 10.1210/endrev/bnaa011.
- Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359–1367. doi: 10.1056/NEJMoa011300.
- Fosse-Edorh S, Mandereau-Bruno L, Piffaretti C (2018). Le poids du diabète en France en 2016 Synthèse épidémiologique. Santé publique France:8p; available from . Accessed 21 April 2020 [Article in French]
Source: PubMed