Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

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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/m ²; 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, HbA _1c, 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.

Electronic supplementary material

The online version of this article (10.1007/s00125-020-05180-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Most cited references 16

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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Author and article information

Contributors

Bertrand Cariou:

ORCID: https://orcid.org/0000-0002-1580-8040

bertrand.cariou@univ-nantes.fr

Samy Hadjadj:

ORCID: https://orcid.org/0000-0001-7110-6994

samy.hadjadj@univ-nantes.fr

Journal

Journal ID (nlm-ta): Diabetologia

Journal ID (iso-abbrev): Diabetologia

Title: Diabetologia

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0012-186X

ISSN (Electronic): 1432-0428

Publication date (Electronic): 29 May 2020

Publication date PMC-release: 29 May 2020

Pages: 1-16

Affiliations

[1 ]Département d’Endocrinologie, Diabétologie et Nutrition, l’institut du thorax, Inserm, CNRS, UNIV Nantes, CHU Nantes, Hôpital Guillaume et René Laennec, 44093 Nantes Cedex 01, France

[2 ]GRID grid.277151.7, ISNI 0000 0004 0472 0371, CIC-EC 1413, Clinique des Données, CHU Nantes, ; Nantes, France

[3 ]GRID grid.11162.35, ISNI 0000 0001 0789 1385, Département d’Endocrinologie, Diabétologie et Nutrition, CHU Amiens, PeriToxUMR_I 01, , Université de Picardie, ; Amiens, France

[4 ]GRID grid.411147.6, ISNI 0000 0004 0472 0283, Département d’Endocrinologie, Diabétologie, Nutrition, , CHU de Angers, ; Angers, France

[5 ]GRID grid.477082.e, Département de Diabétologie, , Centre Hospitalier Sud Francilien, ; Corbeil Essonne, France

[6 ]GRID grid.440367.2, ISNI 0000 0004 0638 5597, Département d’Endocrinologie, Diabétologie et Maladies Métaboliques, , Centre Hospitalier Bretagne Atlantique, ; Vannes, France

[7 ]GRID grid.413875.c, ISNI 0000 0004 0639 4004, Clinique d’Endocrinologique Marc-Linquette, , Hôpital Claude-Huriez, CHRU de Lille, ; Lille, France

[8 ]GRID grid.414007.6, ISNI 0000 0004 1798 6865, Département de Diabétologie, , H.I.A. Begin, ; Saint Mandé, France

[9 ]Fondation Francophone pour la Recherche sur le Diabète (FFRD), Paris, France

[10 ]GRID grid.411158.8, ISNI 0000 0004 0638 9213, Département d’Endocrinologie, Diabétologie et Nutrition, , CHU de Besançon, ; Besançon, France

[11 ]GRID grid.413738.a, ISNI 0000 0000 9454 4367, Département d’Endocrinologie, Diabétologie et Nutrition, Assistance Publique Hôpitaux de Paris, , Université Paris Saclay, Hôpital Antoine Béclère, Clamart, Hôpital Bicêtre, ; Le Kremlin Bicêtre, France

[12 ]GRID grid.477396.8, Sorbonne Université, Assistance Publique Hôpitaux de Paris, Département de Diabétologie, CHU La Pitié Salpêtrière-Charles Foix, Inserm, UMR_S 1138, Centre de Recherche des Cordeliers, Paris 06, , Institute of Cardiometabolism and Nutrition ICAN, ; Paris, France

[13 ]GRID grid.277151.7, ISNI 0000 0004 0472 0371, Département des Maladies Infectieuses et Tropicales, , CHU Nantes, ; Nantes, France

[14 ]GRID grid.411162.1, ISNI 0000 0000 9336 4276, Département des Maladies Infectieuses et Tropicales, , CHU de Poitiers, INSERM U1070, ; Poitiers, France

[15 ]Société de Pathologie Infectieuse de langue Française (SPILF), Paris, France

[16 ]Fédération Française des Diabétiques (FFD), Paris, France

[17 ]GRID grid.413780.9, ISNI 0000 0000 8715 2621, Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, Université Paris 13, Sorbonne Paris Cité, Département d’Endocrinologie, Diabétologie et Nutrition, CRNH-IdF, CINFO, ; Bobigny, France

[18 ]GRID grid.11318.3a, ISNI 0000000121496883, Université Paris 13, Sorbonne Paris Cité, UMR U557 Inserm / U11125 INRAE / CNAM / Université Paris13, Unité de Recherche Epidémiologique Nutritionnelle, ; Bobigny, France

[19 ]GRID grid.411535.7, ISNI 0000 0004 0638 9491, Département d’Endocrinologie et de Diabétologie, , Hôpital de la Conception, Assistance Publique Hôpitaux de Marseille, ; Marseille, France

[20 ]GRID grid.7849.2, ISNI 0000 0001 2150 7757, Département d’Endocrinologie, Diabétologie et Nutrition, Hospices Civils de Lyon, CarMeN Laboratory, Inserm 1060, Lyon, France, , Université Claude Bernard Lyon 1, ; Lyon, France

[21 ]GRID grid.477015.0, ISNI 0000 0004 1772 6836, Département d’Endocrinologie et de Diabétologie, Centre Hospitalier Départemental de Vendée, ; La Roche sur Yon, France

[22 ]GRID grid.414244.3, ISNI 0000 0004 1773 6284, Département d’Endocrinologie et de Diabétologie, , Hôpital Nord, Assistance Publique Hôpitaux de Marseille, ; Marseille, France

[23 ]GRID grid.411149.8, ISNI 0000 0004 0472 0160, Département de Diabétologie, , CHU de Caen, ; Caen, France

[24 ]GRID grid.411766.3, ISNI 0000 0004 0472 3249, Département d’Endocrinologie, , CHU de Brest, ; EA 3878 GETBO, Brest, France

[25 ]Université de Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d’Investigation Clinique de Rennes), Rennes, France

[26 ]Département d’Endocrinologie et de Diabétologie, Centre Hospitalier St. Joseph - St. Luc, Lyon, France

[27 ]GRID grid.412220.7, ISNI 0000 0001 2177 138X, Département d’Endocrinologie, Diabétologie et Nutrition, , Hôpitaux Universitaires de Strasbourg, ; Strasbourg, France

[28 ]GRID grid.5842.b, ISNI 0000 0001 2171 2558, Département d’Endocrinologie, Diabétologie et Nutrition, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Centre de Recherche des Cordeliers, Inserm, U-1138, , Université de Paris, ; Paris, France

[29 ]GRID grid.10400.35, ISNI 0000 0001 2108 3034, Département d’Endocrinologie, Diabétologie et Maladies Métaboliques, CHU de Rouen, , Université de Rouen, ; Rouen, France

[30 ]GRID grid.411296.9, ISNI 0000 0000 9725 279X, Département Diabète et Endocrinologie, , Hôpital Lariboisière, Assistance Publique Hôpitaux de Paris, ; Paris, France

[31 ]Paris Diderot–Paris VII Université, Paris, France

[32 ]GRID grid.7452.4, ISNI 0000 0001 2217 0017, Inserm UMRS 1138, Université Paris Diderot–Paris VII, Sorbonne Paris Cité, ; Paris, France

[33 ]GRID grid.11166.31, ISNI 0000 0001 2160 6368, Université de Poitiers, CIC Inserm 1402, Poitiers, Médecine Intensive Réanimation, ; Poitiers, France

[34 ]Centre d’Investigation Clinique CIC 1402, Université de Poitiers, Inserm, CHU de Poitiers, Poitiers, France

[35 ]GRID grid.157868.5, ISNI 0000 0000 9961 060X, Département d’Endocrinologie, Diabète, Nutrition et CIC Inserm 1411, , CHU de Montpellier, ; Montpellier, France

[36 ]GRID grid.7849.2, ISNI 0000 0001 2150 7757, Centre du Diabète DIAB-eCARE, Hospices Civils de Lyon et Laboratoire CarMeN, Inserm, INRA, INSA, , Université Claude Bernard Lyon 1, ; Lyon, France

[37 ]GRID grid.484642.8, ISNI 0000 0001 0807 394X, Société Francophone du Diabète (SFD), ; Paris, France

[38 ]GRID grid.11417.32, ISNI 0000 0001 2353 1689, Département d’Endocrinologie, Diabétologie et Nutrition, CHU Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, UMR1048 Inserm/UPS, , Université de Toulouse, ; Toulouse, France

[39 ]GRID grid.412370.3, ISNI 0000 0004 1937 1100, Assistance Publique Hôpitaux de Paris, Saint-Antoine Hospital, Reference Center of Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Department of Endocrinology, ; Paris, France

[40 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Sorbonne University, Inserm UMRS 938, Saint-Antoine Research Center, ; Paris, France

Author information

Bertrand Cariou https://orcid.org/0000-0002-1580-8040

Samy Hadjadj https://orcid.org/0000-0001-7110-6994

Matthieu Wargny https://orcid.org/0000-0001-6027-9486

Matthieu Pichelin https://orcid.org/0000-0002-6822-6132

Abdallah Al-Salameh https://orcid.org/0000-0002-7951-9926

Coralie Amadou https://orcid.org/0000-0002-0581-7592

Sophie Borot https://orcid.org/0000-0001-6240-8253

Olivier Bourron https://orcid.org/0000-0001-7348-7161

David Boutoille https://orcid.org/0000-0001-9722-2029

France Cazenave-Roblot https://orcid.org/0000-0003-4325-023X

Emmanuel Cosson https://orcid.org/0000-0002-8785-3385

Patrice Darmon https://orcid.org/0000-0003-1726-2296

Emmanuel Disse https://orcid.org/0000-0002-4045-0503

Bénédicte Gaborit https://orcid.org/0000-0002-4180-158X

Michael Joubert https://orcid.org/0000-0002-8731-7355

Bruno Laviolle https://orcid.org/0000-0002-9541-6708

Lucien Marchand https://orcid.org/0000-0001-9101-5002

Laurent Meyer https://orcid.org/0000-0003-3687-5522

Louis Potier https://orcid.org/0000-0001-6268-7360

Jean-Pierre Riveline https://orcid.org/0000-0001-7991-0741

René Robert https://orcid.org/0000-0001-5989-5409

Pierre-Jean Saulnier https://orcid.org/0000-0003-1862-4252

Ariane Sultan https://orcid.org/0000-0002-9540-8222

Jean-François Thébaut https://orcid.org/0000-0003-4926-9943

Charles Thivolet https://orcid.org/0000-0002-0696-974X

Camille Vatier https://orcid.org/0000-0001-8342-1596

Ronan Roussel https://orcid.org/0000-0003-2292-8363

Jean-François Gautier https://orcid.org/0000-0001-6458-2001

Pierre Gourdy https://orcid.org/0000-0002-5362-3813

Article

Publisher ID: 5180

DOI: 10.1007/s00125-020-05180-x

PMC ID: 7256180

PubMed ID: 32472191

SO-VID: b20f354a-c6a9-47cc-b823-7e4dc3e79185

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 23 April 2020

Date accepted : 7 May 2020

Funding

Funded by: Fondation Francophone pour la Recherche sur le Diabète

Award ID: CORONADO Initiative Emergency Grant

Funded by: FundRef http://dx.doi.org/10.13039/100007542, Air Liquide;

Award ID: CORONADO Initiative Emergency grant

Funded by: Sociéte Francophone du Diabète

Award ID: CORONADO Initiative Emergency Grant

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Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

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Abstract

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Trial registration

Electronic supplementary material

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 16

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical Characteristics of Coronavirus Disease 2019 in China

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

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Cited by 411

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