Heightened ACE Activity and Unfavorable Consequences in COVID-19 Diabetic Subjects

Sandooja, Rashi; Vura, Naga Venkata Rama Krishna; Morocco, Michael

doi:10.1155/2020/7847526

Cited by 17 publications

(15 citation statements)

References 21 publications

(30 reference statements)

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“…Our analysis demonstrated that asymptomatic children with diabetes and/or recent contact with a COVID-19 case, as well as those tested for surveillance purposes (rather than for pre-procedure or pre-admission purposes), had significantly higher estimated risk of being in the quartile with the highest viral burden. Despite small numbers of diabetic patients in our study, the finding that diabetic children were more at risk of having high viral loads requires further dedicated investigation, as it is consistent with studies in adults that have demonstrated more severe disease and poorer prognosis in patients with diabetes (14,15). The asymptomatic population with known/recent COVID-19 contact overlapped with the population tested for surveillance purposes, though not perfectly (as some pre-procedure or pre-admission patients had contacts).…”

Section: Resultssupporting

confidence: 87%

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs

et al. 2020

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The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with SARS-CoV-2 is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay, and converted to estimated VL (copies/mL) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 vs. 197 ages 0-4; 79 vs 97 ages 5-9; 69 vs 75 ages 10-13; 73 vs 109 ages 14-17) were compared. The median adjusted Ct value in asymptomatic children was 10.3 cycles higher than for symptomatic children (p< 0.0001), and VL 3-4 logs lower (p<0.0001); differences were consistent (p<0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (OR 6.5, p = 0.01), recent contact (OR 2.3, p = 0.02), and testing for surveillance (OR 2.7, p = 0.005) had higher estimated risk of having a Ct value in the lowest quartile than children without, while immunocompromise had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in the nasopharynx/oropharynx than symptomatic children, but timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

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Section: Resultssupporting

confidence: 87%

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs

et al. 2020

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“…The association between COVID-19 and hyperglycemia in elderly patients with T2D might reflect metabolic inflammation and exaggerated cytokine release. SARS-CoV2 infection can deteriorate glycemic control by enhancing insulin resistance and impaired insulin secretion, thus leading to DKA [11,55]. The unique interactions between SARS-CoV-2 and the RAAS might provide yet another mechanism in the pathophysiology of DKA first by direct entry of SARS-CoV-2 into pancreatic islet cells worsening b-cell injury, and second by downregulation of ACE2 after viral entry that can lead to unopposed angiotensin II and subsequent insulin secretion impedance [56,57].…”

Section: Discussionmentioning

confidence: 99%

Diabetes-related acute metabolic emergencies in COVID-19 patients: a systematic review and meta-analysis

Papadopoulos

Koutroulos²,

Zikoudi³

et al. 2021

Diabetol Int

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Aims COVID-19 is associated with diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and euglycaemic DKA (EDKA); however, evidence regarding parameters affecting outcome and mortality rates is scarce. Methods A systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January 2020 to 7 January 2021 to identify all studies describing clinical profile, outcome and mortality rates regarding DKA, HHS, DKA/HHS and EDKA cases in COVID-19 patients. The appropriate Joanna Briggs Institute tools were used for quality assessment; quality of evidence was approached using GRADE. Univariate and multivariate analyses were used to assess correlations between clinical characteristics and outcome based on case reports. Combined mortality rates (CMR) were estimated from data reported in case report series, cross-sectional studies, and meta-analyses. The protocol was submitted to PROSPERO (ID: 229356/230737). Results From 312 identified publications, 44 were qualitatively and quantitatively analyzed. Critical COVID-19 necessitating ICU (P = 3 × 10-8), DKA/HHS presence (P = 0.021), and AKI (P = 0.037) were independently correlated with death. Increased COVID-19 severity (P = 0.003), elevated lactates (P < 0.001), augmented anion gap (P < 0.001), and AKI (P = 0.002) were associated with DKA/HHS. SGLT-2i were linked with EDKA (P = 0.004) and negatively associated with AKI (P = 0.023). CMR was 27.1% (95% CI 11.2-46.9%) with considerable heterogeneity (I 2 = 67%). Conclusion Acute diabetes-related metabolic emergencies in COVID-19 patients lead to increased mortality; key determinants are critical COVID-19 illness, coexistence of DKA/HHS and AKI. Previous SGLT-2i treatment, though associated with EDKA, might preserve renal function in COVID-19 patients.

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“…The association between Covid-19 and hyperglycemia in elderly patients with T2D might reflect metabolic inflammation and exaggerated cytokine release. SARS-CoV2 infection can deteriorate glycemic control, involving both profound insulin resistance and impaired insulin secretion, together leading to DKA and increasing hospital admissions and mortality [10,92].…”

Section: Discussionmentioning

confidence: 99%

Acute Metabolic Emergencies in Diabetes and COVID-19: a systematic review and meta-analysis of case reports

Papadopoulos¹,

Koutroulos²,

Zikoudi³

et al. 2021

Preprint

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BackgroundCOVID-19 is associated with DKA (Diabetic Ketoacidosis), HHS (Hyperglycaemic Hyperosmolar State) and EDKA (Euglycaemic DKA). High mortality has been observed in COVID-19-related diabetic ketoacidosis; however, evidence is scarce.MethodsA systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January to December 2020 to identify all case reports describing DKA, HHS, and EDKA, in COVID-19 patients. The Joanna Briggs Institute critical appraisal checklist for case reports was used for quality assessment. Univariate and multivariate analysis assessed correlations of study origin, combined DKA/HHS, age, BMI, HbA1c, administered antidiabetics, comorbidities, symptoms onset, disease status (DS), CRP, ferritin, d-dimers, glucose, osmolarity, pH, bicarbonates, ketones, lactates, β-hydroxybutyric acid, anion gap, and acute kidney injury (AKI) with outcome. The relevant protocol was submitted to PROSPERO database (ID: 229356).ResultsFrom 312 identified publications, 41 including 71 cases analyzed qualitatively and quantitatively. The types of acute metabolic emergencies observed were DKA (45/71, 63.4%), EDKA (6/71, 8.5%), combined DKA/HHS (19/71, 26.8%), and HHS (1/71, 1.4%). Overall mortality was 32.4% (22/68 patients; 3 missing). Multivariate analysis by classical regression demonstrated that COVID-19 DS4 (P=3•10−8), presence of DKA/HHS (P=0.021), and development of AKI (P=0.037) were all independently correlated with death. Increased DS (P=0.003), elevated lactates (P<0.001), augmented anion gap (P<0.001), and presence of AKI (P=0.002) were associated with DKA/HHS. SGLT-2i administration was linked with EDKA (P=0.004); however, a negative association with AKI was noted (P=0.023).ConclusionCOVID-19 intertwines with acute metabolic emergencies in diabetes leading to increased mortality. Key determinants are critical COVID-19 illness, coexistence of DKA/HHS and AKI. Awareness of clinicians to timely assess them might enable early detection and immediate treatment commencing. As previous treatment with was negatively associated with AKI, thus implying a prophylactic effect on renal function, the issue of discontinuation of SGLT-2i in COVID-19 patients remains to be further evaluated.Key messagesWhat is already known on this subject▸Diabetes mellitus (DM) is a risk factor for poor outcomes in COVID-19 patients.▸Diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) are not rare in COVID-19 diabetic and non-diabetic patients; key determinants of outcome remain unknown.What this study adds▸COVID-19 intertwines with acute metabolic emergencies in diabetes leading to increased mortality; key determinants are critical COVID-19 illness, coexistence of DKA and HHS as well as development of acute kidney injury.▸SGLT2-i administration is linked with euglycaemic DKA in patients with COVID-19, though preserving renal function.

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Heightened ACE Activity and Unfavorable Consequences in COVID-19 Diabetic Subjects

Cited by 17 publications

References 21 publications

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs

Diabetes-related acute metabolic emergencies in COVID-19 patients: a systematic review and meta-analysis

Acute Metabolic Emergencies in Diabetes and COVID-19: a systematic review and meta-analysis of case reports

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