Influence of diabetes mellitus on the severity and fatality of SARS‐CoV‐2 (COVID‐19) infection

Wu, Jing; Zhang, Jingqi; Sun, Xin; Wang, Lijuan; Xu, Yunfang; Zhang, Yuanyuan; Liu, Xingxiang; Dong, Chen

doi:10.1111/dom.14105

Cited by 124 publications

(114 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Independent risk factors associated with severe COVID-19 include male sex, increased age, and presence of comorbidities [ 6 , [8] , [9] , [10] , [36] , [37] , [38] ]. To evaluate whether the spatial distribution and abundance of ACE2 protein in the lower respiratory tract differed by these risk factors, we scored tissues for ACE2 protein detection ( Supplemental Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…2) Control group was defined as lacking these chronic comorbidities and lacking clinical lung disease. The definition of chronic comorbidities was informed by reported independent risk factors for mortality in COVID-19 [8] , [9] , [10] . The cumulative cohort included 29 cases (15 chronic comorbidities and 14 controls) with a broad range of ages (0•5 – 71 years) and both sexes were represented (13 female and 16 male).…”

Section: Methodsmentioning

confidence: 99%

“…SARS-CoV-2 is the etiologic agent of coronavirus disease 2019 (COVID-19) which was first recognized in December 2019 and has now reached pandemic proportions [ 2 , 4 ]. SARS-CoV-2 infection can be fatal, with the risk for increased disease severity correlating with advanced age and underlying comorbidities, while children and younger individuals generally have milder disease [5] , [6] , [7] , [8] , [9] , [10] , [11] . These trends in disease severity could reflect differences in ACE2 distribution and expression in the respiratory tract.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Ortiz¹,

Thurman²,

Pezzulo³

et al. 2020

EBioMedicine

167

146

View full text Add to dashboard Cite

Background Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. Materials and methods We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. Findings Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. Interpretation These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Ortiz¹,

Thurman²,

Pezzulo³

et al. 2020

EBioMedicine

167

146

View full text Add to dashboard Cite

show abstract

“…Although several studies and meta-analyses have shown that patients with diabetes have a significantly higher risk of severe COVID-19 and increased mortality rates [14][15][16], A c c e p t e d M a n u s c r i p t the impact of hyperglycemia itself, rather than the presence of DM, has not been sufficiently described in non-critically patients hospitalized with COVID-19.…”

Section: Hyperglycemia Upregulates Ace2 Expression and Induces Glycosmentioning

confidence: 99%

Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19 regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry

et al. 2020

View full text Add to dashboard Cite

Background Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. Methods This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140–180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality. Results Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140–180 mg) and 41.1% (>180 mg/dL), p <.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p <.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31–1.73) (BG 140–180 mg/dL; HR 1.48; 95%CI: 1.29–1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. Conclusions Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.

show abstract

“…SARS-CoV-2 is the etiologic agent of coronavirus disease 2019 (COVID- 19) which was first recognized in December 2019 and has now reached pandemic proportions (2,4). SARS-CoV-2 infection can be fatal, with the risk for increased disease severity correlating with advanced age and underlying comorbidities, while children and younger individuals generally have milder disease (5)(6)(7)(8)(9)(10)(11). These trends in disease severity could reflect differences in ACE2 distribution and expression in the respiratory tract.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Bezara

Thurman

Pezzulo

et al. 2020

Preprint

View full text Add to dashboard Cite

15Running title: Expression of ACE2 in the human respiratory tract 16 17 Impact: The mapping of ACE2, the receptor for SARS-CoV-2, to specific anatomical regions 18 and to particular cell types in the human respiratory tract will help guide future studies and 19 provide molecular targets for antiviral therapies. We saw no increase of receptor expression in 20 the presence of known risk factors for severe coronavirus disease 2019. 21 22 Abstract: 35 Rationale: Zoonotically transmitted coronaviruses are responsible for three disease 36 outbreaks since 2002, including the current coronavirus disease 2019 pandemic, caused by 37 SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding 38 the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the cellular 39 receptor for SARS-CoV-2. Receptor expression on the cell surface facilitates viral binding and 40 entry. However, reports of the abundance and distribution of ACE2 expression in the respiratory 41 tract are limited and conflicting. Objectives: To determine ACE2 expression in the human 42 respiratory tract and its association with demographic and clinical characteristics. Methods: 43Here, we systematically examined human upper and lower respiratory tract cells using single-cell 44 RNA sequencing and immunohistochemistry to determine where the receptor is expressed. 45Measurements and main results: Our results reveal that ACE2 expression is highest within the 46 sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe 47 disease development, respectively. In the lung parenchyma where severe disease occurs, ACE2 48 was found on the apical surface of a small subset of alveolar type II cells. We saw no increase of 49 receptor expression in the presence of known risk factors for severe coronavirus disease 2019. 50Conclusions: The mapping of ACE2 to specific anatomical regions and to particular cell types in 51 the respiratory tract will help guide future studies and provide molecular targets for antiviral 52 therapies. 53 54 Word count: 223 55

show abstract

Influence of diabetes mellitus on the severity and fatality of SARS‐CoV‐2 (COVID‐19) infection

Cited by 124 publications

References 45 publications

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19 regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Contact Info

Product

Resources

About