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.

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.

PurposeLittle is known on the mortality rate in COVID-19 related acute metabolic emergencies, namely diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS), combined DKA/HHS, and euglycaemic diabetic ketoacidosis (EDKA).MethodsA systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January 1, 2020 to January 9, 2021 to identify all case report series, cross-sectional studies, and meta-analyses of case reports describing mortality rate in DKA, HHS, and EDKA, in COVID-19 patients. The Joanna Briggs Institute critical appraisal checklist for case reports was used for quality assessment.ResultsFrom 313 identified publications, 4 fulfilled the inclusion criteria and analyzed qualitatively and quantitatively. A systematic review and meta-analysis with subgroup analyses examined mortality rate in a total of 152 COVID-19 patients who had developed DKA, HHS, combined DKA/HHS, or EDKA. Combined mortality rate and confidence intervals (CI) were estimated using random effects model. The study was registered to PROSPERO database (ID: 230737).ResultsCombined mortality rate was found to be 27.1% [95% CI: 11.2-46.9%]. Heterogeneity was considerable (I2=83%; 95% CI: 56-93%), corrected to 67% according to Von Hippel adjustment for small meta-analyses. Funnel plot presented no apparent asymmetry; Egger’s and Begg’s test yielded in P=0.44 and P=0.50, respectively. Sensitivity analysis failed to explain heterogeneity.ConclusionCOVID-19 related acute metabolic emergencies (DKA, HHS, and EDKA) are characterized by considerable mortality; thus, clinicians should be aware of timely detection and immediate treatment commencing.