Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports

Abstract Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, and whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.

[1]  S. Sookoian,et al.  Age but not sex may explain the negative effect of arterial hypertension and diabetes on COVID-19 prognosis , 2020, Journal of Infection.

[2]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[3]  G. Mancia,et al.  Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19 , 2020, The New England journal of medicine.

[4]  F. Strollo,et al.  COVID-19 infection in Italian people with diabetes: Lessons learned for our future (an experience to be used) , 2020, Diabetes Research and Clinical Practice.

[5]  M. Zheng,et al.  Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease , 2020, Metabolism.

[6]  D. Drucker Coronavirus infections and type 2 diabetes-shared pathways with therapeutic implications , 2020, Endocrine reviews.

[7]  Avik Ray,et al.  Metformin in COVID-19: A possible role beyond diabetes , 2020, Diabetes Research and Clinical Practice.

[8]  C. Mantzoros,et al.  Commentary: COVID-19 and diabetes mellitus: What we know, how our patients should be treated now, and what should happen next , 2020, Metabolism.

[9]  M. Zuin,et al.  Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome , 2020, Journal of Clinical Virology.

[10]  Erkan Cüre,et al.  Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis , 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews.

[11]  M. Bajaj,et al.  Diabetes and covid-19: a global health challenge , 2020, BMJ Open Diabetes Research & Care.

[12]  S. Bhadada,et al.  Should anti-diabetic medications be reconsidered amid COVID-19 pandemic? , 2020, Diabetes Research and Clinical Practice.

[13]  Huihui Ren,et al.  Clinical characteristics and outcomes of patients with severe covid-19 with diabetes , 2020, BMJ Open Diabetes Research & Care.

[14]  Hangyuan Guo,et al.  Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis , 2020, Journal of Infection.

[15]  Fang Lei,et al.  Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes , 2020, Cell Metabolism.

[16]  Norbert Stefan,et al.  Obesity and impaired metabolic health in patients with COVID-19 , 2020, Nature Reviews Endocrinology.

[17]  S. Alzghari,et al.  Supportive Treatment with Tocilizumab for COVID-19: A Systematic Review , 2020, Journal of Clinical Virology.

[18]  A J Scheen,et al.  Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections. , 1992, Diabete & metabolisme.

[19]  D. Spandidos,et al.  Obesity - a risk factor for increased COVID-19 prevalence, severity and lethality , 2020, Molecular medicine reports.

[20]  Marc A Pfeffer,et al.  Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19 , 2020, The New England journal of medicine.

[21]  K. Khunti,et al.  Therapeutic uncertainties in people with cardiometabolic diseases and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or COVID‐19) , 2020, Diabetes, obesity & metabolism.

[22]  Geltrude Mingrone,et al.  Practical recommendations for the management of diabetes in patients with COVID-19 , 2020, The Lancet Diabetes & Endocrinology.

[23]  R. José,et al.  Does Coronavirus Disease 2019 Disprove the Obesity Paradox in Acute Respiratory Distress Syndrome? , 2020, Obesity.

[24]  Ying Yao,et al.  Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia. , 2020, Journal of the American Society of Nephrology : JASN.

[25]  Ritesh Gupta,et al.  Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations , 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews.

[26]  R. Ruslami,et al.  Type 2 Diabetes and its Impact on the Immune System , 2020, Current diabetes reviews.

[27]  P. Ye,et al.  Longitudinal Association Between Markers of Liver Injury and Mortality in COVID‐19 in China , 2020, Hepatology.

[28]  H. Jneid,et al.  Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the JAHA Editors , 2020, Journal of the American Heart Association.

[29]  Wei Wang,et al.  Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis , 2020, European Respiratory Journal.

[30]  Anna Stachel,et al.  Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  Rui Ji,et al.  Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis , 2020, International Journal of Infectious Diseases.

[32]  S. Manfrini,et al.  Obesity and SARS‐CoV‐2: A population to safeguard , 2020, Diabetes/metabolism research and reviews.

[33]  D. Kass,et al.  Obesity could shift severe COVID-19 disease to younger ages , 2020, The Lancet.

[34]  D. Cook,et al.  Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: long-term follow-up of a subgroup of patients from the NICE-SUGAR study , 2015, Intensive Care Medicine.

[35]  O. Pfister,et al.  SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19? , 2020, European heart journal.

[36]  A. Malhotra,et al.  Potential influences of obstructive sleep apnea and obesity on COVID-19 severity. , 2020, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[37]  Xuexian Fang,et al.  Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis , 2020, Research.

[38]  S. Legrand-Poels,et al.  Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue , 2013, Diabetologia.

[39]  G. Iacobellis COVID-19 and diabetes: Can DPP4 inhibition play a role? , 2020, Diabetes Research and Clinical Practice.

[40]  A. Avogaro,et al.  Prevalence and impact of diabetes among people infected with SARS-CoV-2 , 2020, Journal of Endocrinological Investigation.

[41]  R. Pranata,et al.  Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression , 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews.

[42]  Akhtar Hussain,et al.  COVID-19 and diabetes: Knowledge in progress , 2020, Diabetes Research and Clinical Practice.

[43]  Qingbo Xu,et al.  Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19 , 2020, Circulation research.

[44]  A. Malavazos,et al.  Targeting the Adipose Tissue in COVID‐19 , 2020, Obesity.

[45]  B. Jiang,et al.  Comorbidities and multi-organ injuries in the treatment of COVID-19 , 2020, The Lancet.

[46]  G. Umpierrez,et al.  Individualizing Inpatient Diabetes Management During the Coronavirus Disease 2019 Pandemic , 2020, Journal of diabetes science and technology.

[47]  A. Abdelhafiz,et al.  Age, frailty and diabetes – triple jeopardy for vulnerability to COVID-19 infection , 2020, EClinicalMedicine.

[48]  Leora I. Horwitz,et al.  Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study , 2020, BMJ.

[49]  Eun Ji Kim,et al.  Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. , 2020, JAMA.

[50]  B. Kavanagh,et al.  Clinical practice. Glycemic control in the ICU. , 2010, The New England journal of medicine.

[51]  D. Mathieu,et al.  High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) Requiring Invasive Mechanical Ventilation , 2020, Obesity.

[52]  David C. Klonoff,et al.  Letter to the Editor: COVID-19 in patients with diabetes: Risk factors that increase morbidity , 2020, Metabolism.

[53]  N. Caplice,et al.  Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation, and Cytokine Amplification in Coronavirus Disease 2019? , 2020, Obesity.

[54]  G. Paolisso,et al.  Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients , 2020, Diabetes & Metabolism.

[55]  R. Muniyappa,et al.  COVID-19 pandemic, coronaviruses, and diabetes mellitus , 2020, American journal of physiology. Endocrinology and metabolism.

[56]  R. José,et al.  Does Coronavirus Disease 2019 Disprove the Obesity Paradox in Acute Respiratory Distress Syndrome? , 2020, Obesity (Silver Spring, Md.).

[57]  Jian Chen,et al.  COVID‐19 infection may cause ketosis and ketoacidosis , 2020, Diabetes, obesity & metabolism.

[58]  Y. Leo,et al.  Association of higher body mass index (BMI) with severe coronavirus disease 2019 (COVID-19) in younger patients , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[59]  A. Troxel,et al.  Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19 , 2020, The New England journal of medicine.

[60]  J. Saavedra Angiotensin receptor blockers and COVID-19 , 2020, Pharmacological Research.

[61]  Jin-Kui Yang,et al.  Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes , 2009, Acta Diabetologica.

[62]  M. Rizzo,et al.  COVID-19 and diabetes management: What should be considered? , 2020, Diabetes Research and Clinical Practice.

[63]  A. Ceriello Hyperglycemia and the worse prognosis of COVID-19. Why a fast blood glucose control should be mandatory , 2020, Diabetes Research and Clinical Practice.

[64]  S. Flint,et al.  COVID-19 and obesity—lack of clarity, guidance, and implications for care , 2020, The Lancet Diabetes & Endocrinology.

[65]  Stephane Heritier,et al.  Intensive versus conventional glucose control in critically ill patients. , 2009, The New England journal of medicine.

[66]  W. Hong,et al.  Hypertransaminasemia in the course of infection with SARS-CoV-2: Incidence and pathogenetic hypothesis , 2020, World journal of clinical cases.

[67]  Bo Li,et al.  Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China , 2020, Clinical Research in Cardiology.