PurposeLittle is known on the mortality rate in COVID-19 MESHD related acute metabolic emergencies, namely diabetic ketoacidosis MESHD ( DKA MESHD), hyperglycaemic hyperosmolar MESHD state (HHS), combined DKA MESHD/HHS, and euglycaemic diabetic ketoacidosis MESHD ( EDKA MESHD). 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 MESHD, HHS, and EDKA MESHD, in COVID-19 MESHD 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 MESHD patients who had developed DKA MESHD, HHS, combined DKA MESHD/HHS, or EDKA MESHD. 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 MESHD adjustment for small meta-analyses. Funnel plot presented no apparent asymmetry; Eggers and Beggs test yielded in P=0.44 and P=0.50, respectively. Sensitivity analysis failed to explain heterogeneity. Conclusion COVID-19 MESHD related acute metabolic emergencies ( DKA MESHD, HHS, and EDKA MESHD) are characterized by considerable mortality; thus, clinicians should be aware of timely detection and immediate treatment commencing.

Introduction COVID-19 MESHD is associated with DKA MESHD ( Diabetic Ketoacidosis MESHD), HHS ( Hyperglycaemic Hyperosmolar MESHD State) and EDKA (Euglycaemic DKA MESHD). High mortality has been observed in COVID-19 MESHD-related diabetic ketoacidosis MESHD; however, evidence is scarce. Patients and 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 MESHD, HHS, and EDKA, in COVID-19 MESHD 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 MESHD/HHS, age, BMI, HbA1c, administered antidiabetics, comorbidities, symptoms onset, disease status, CRP HGNC, ferritin, d-dimers, glucose, osmolarity, pH, bicarbonates, ketones, lactates, {beta}-hydroxybutyric acid, anion gap, and acute kidney injury MESHD ( AKI MESHD) with outcome. ResultsFrom 312 identified publications, 41 including 71 cases analyzed qualitatively and quantitatively. Multivariate analysis demonstrated that COVID-19 MESHD disease status 4 (P<0.001), AKI MESHD (P<0.001), pH [≤]7.12 (P=0.032), and osmolarity [≥]324 (P=0.034), are all independently correlated with death MESHD. COVID-19 MESHD Disease Status 4 (P=3*10-8), combined DKA MESHD/HHS (P=0.021), and AKI MESHD (P=0.037) are independently correlated with death MESHD. Conclusion COVID-19 MESHD intertwines with acute metabolic emergencies MESHD in diabetes MESHD leading to increased mortality; key determinants are critical COVID-19 MESHD illness, co-presence of ketoacidosis and hyperosmosis MESHD and AKI MESHD.

New-onset DM MESHD or unmasking existing one, with or without metabolic complications, has been reported in SARS CoV-2 infection MESHD. New-onset DM MESHD in association with HHS alone or combination with DKA is uncommon but a possible manifestation of SARS CoV-2 infection MESHD that poses management challenges where the outcome may be worst.

Tocilizumab is used for treating moderate-severe Covid-19 MESHD pneumonia MESHD by targeting IL-6 receptors ( IL-6R HGNC) and reducing cytokine release, but the pooled rate ratio among diabetic MESHD patients with adverse vs those with the more favorable course was 2.26. To date, the hyperglycemia MESHD has been shown to increase IL-6 HGNC and IL-6R HGNC, which has been suggested as a severity predictor in lung diseases of Covid-19 MESHD patients. However, there are no data about the effects of tocilizumab therapy on outcomes of hyperglycemic Covid-19 MESHD patients with pneumonia MESHD. To investigate this unsolved need, 475 Covid-19 MESHD positive patients were retrospectively studied since March 1st, 2020. Among them, 78 patients with pneumonia disease MESHD and treated with tocilizumab were further evaluated for a severe outcome (encompassing both the use of mechanical ventilation and/or death MESHD). Thirty-one (39.7%) hyperglycemic and 47 (60.3%) normoglycemic Covid-19 MESHD positive patients (blood glucose levels >140 mg/dl, at admission and/or during hospital stay) were evaluated. Noteworthy, 20 (64%) of hyperglycemic MESHD and 11 (23.4%) of normoglycemic patients were also diabetics (P<0.01). At admission, more elevated IL-6 HGNC levels in hyperglycemic MESHD patients were found and persists even after Tocilizumab administration. In a risk adjusted Cox-regression analysis, Tocilizumab in hyperglycemic did not attenuate the risks of severe outcome as did in normoglycemic patients (p<0.009). Therefore, we could conclude that reduced effects of Tocilizumab in hyperglycemic MESHD patients may due to the higher plasma IL-6 HGNC levels. Interestingly, when we added IL-6 HGNC levels in a Cox regression model the significance for the tocilizumab effect was lost (p<0.07). In this context, our observations evidence that optimal Covid-19 MESHD infection management with tocilizumab is not achieved during hyperglycemia MESHD both in diabetic and non-diabetic MESHD patients.