COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

Vitamin D Levels Are Associated With Blood Glucose and BMI in COVID-19 Patients, Predicting Disease Severity.

CONTEXT: A high prevalence of vitamin D (VD) deficiency in COVID-19 patients has been reported and hypothesized to increase COVID-19 severity likely because of its negative impact on immune and inflammatory responses. Furthermore, clear associations between hypovitaminosis D and fat body mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized. OBJECTIVE: The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, body mass index (BMI), blood glucose (GLU), and disease severity. METHODS: Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD metabolism. 25-Hydroxyvitamin D levels, plasma GLU levels, BMI, and inflammatory parameters were evaluated at admission. RESULTS: A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD deficiency was found in 68.2% of patients. VD deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma GLU, BMI, neutrophil/lymphocyte ratio, C-reactive protein, and interleukin 6. Patients with both hypovitaminosis D and diabetes mellitus, as well those with hypovitaminosis D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions. CONCLUSION: We showed, for the first-time, a strict association of VD levels with blood GLU and BMI in COVID-19 patients. VD deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.

Differentiating transient from persistent diabetic range hyperglycemia in a cohort of people completing tuberculosis treatment in Dhaka, Bangladesh.

BACKGROUND: In recent non-pandemic periods, tuberculosis (TB) has been the leading killer worldwide from a single infectious disease. Patients with DM are three times more likely to develop active TB and poor treatment outcomes. Single glycemic measurements at TB diagnosis may inaccurately diagnose or mischaracterize DM severity. Data are limited regarding glycemic dynamics from TB diagnosis through treatment. METHODS: Prospective study of glycemia dynamics in response to TB treatment measured glycosylated haemoglobin (HbA1c) in patients presenting to TB screening centres in Bangladesh to determine the prevalence and risk factors of hyperglycemia before and at TB treatment completion. RESULTS: 429 adults with active TB disease were enrolled and divided into groups based on history of DM and initial HbA1c range: normoglycemia, prediabetes, and DM. DM was diagnosed in 37%. At treatment completion,14(6%) patients from the normoglycemia and prediabetes groups had HbA1c>6.5%, thus increasing the prevalence of DM to 39%. The number needed to screen to diagnose one new case of DM at TB diagnosis was 5.7 and 16 at treatment completion in the groups without DM. Weight gain>5% at treatment completion significantly increased the risk of hyperglycemia in the groups without DM at TB diagnosis (95% CI 1.23-26.04, p<0.05). CONCLUSION: HbA1c testing prior to and at TB treatment completion found a high prevalence of prediabetes and DM, including a proportion found at treatment completion and commonly in people with a higher percentage of weight gain. Further longitudinal research is needed to understand the effects of TB disease and treatment on insulin resistance and DM complications.

Blood Hemoglobin Substantially Modulates the Impact of Gender, Morbid Obesity, and Hyperglycemia on COVID-19 Death Risk: A Multicenter Study in Italy and Spain.

Background: Hyperglycemia and obesity are associated with a worse prognosis in subjects with COVID-19 independently. Their interaction as well as the potential modulating effects of additional confounding factors is poorly known. Therefore, we aimed to identify and evaluate confounding factors affecting the prognostic value of obesity and hyperglycemia in relation to mortality and admission to the intensive care unit (ICU) due to COVID-19. Methods: Consecutive patients admitted in two Hospitals from Italy (Bologna and Rome) and three from Spain (Barcelona and Girona) as well as subjects from Primary Health Care centers. Mortality from COVID-19 and risk for ICU admission were evaluated using logistic regression analyses and machine learning (ML) algorithms. Results: As expected, among 3,065 consecutive patients, both obesity and hyperglycemia were independent predictors of ICU admission. A ML variable selection strategy confirmed these results and identified hyperglycemia, blood hemoglobin and serum bilirubin associated with increased mortality risk. In subjects with blood hemoglobin levels above the median, hyperglycemic and morbidly obese subjects had increased mortality risk than normoglycemic individuals or non-obese subjects. However, no differences were observed among individuals with hemoglobin levels below the median. This was particularly evident in men: those with severe hyperglycemia and hemoglobin concentrations above the median had 30 times increased mortality risk compared with men without hyperglycemia. Importantly, the protective effect of female sex was lost in subjects with increased hemoglobin levels. Conclusions: Blood hemoglobin substantially modulates the influence of hyperglycemia on increased mortality risk in patients with COVID-19. Monitoring hemoglobin concentrations seem of utmost importance in the clinical settings to help clinicians in the identification of patients at increased death risk.

Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition.

We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer (p = 0.004), and needed more frequently insulin infusion therapy (p = 0.022) to control stress hyperglycemia. The need for insulin infusion therapy was associated with higher energy (p = 0.001) and glucose delivered through artificial nutrition (p = 0.040). Those patients with stress hyperglycemia showed higher ICU stays (23 ± 17 vs. 11 ± 13 days, p = 0.007). Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU (r = -0.476, p = 0.001) and at days 2 (r = -0.409, p = 0.007) and 3 (r = -0.351, p = 0.049). In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.

A practical guidance on the use of intravenous insulin infusion for management of inpatient hyperglycemia: Intravenous Insulin Infusion for Management of Inpatient Hyperglycemia.

BACKGROUND: We aim to provide a practical guidance on the use of intravenous insulin infusion for managing inpatient hyperglycemia. METHODS AND RESULTS: This document was formulated based on the review of available literature and personal experience of authors. We have used various case scenarios to illustrate variables which should be taken into account when deciding adjustments in infusion rate, including but not restricted to ambient blood glucose level and magnitude of blood glucose change in the previous hour. CONCLUSION: The guidance can be generalized to any situation where dedicated protocols are lacking, trained manpower is not available and resource constraints are present.

A Retrospective Study of 268 Patients with SARS-CoV-2 Infection to Evaluate the Association Between Blood Glucose and Severity of COVID-19 Pneumonia and Patient Mortality.

BACKGROUND Diabetes is one of the most commonly reported comorbidities among patients infected with SARS-CoV-2. This retrospective study of patients with SARS-CoV-2 infection was conducted to evaluate the association between blood glucose levels and the severity of COVID-19 pneumonia and patient mortality. MATERIAL AND METHODS A total of 268 patients with confirmed SARS-CoV-2 infection were included in this retrospective study. We obtained demographic characteristics, clinical symptoms, laboratory data, and survival information from patients' electronic medical records. Blood glucose was measured on admission to the hospital. Comorbidities, including hypertension, diabetes, chronic kidney disease, chronic liver disease, chronic obstructive pulmonary disease, and cardiovascular disease, were collected by self-reported medical history. RESULTS Significantly higher risks of severe COVID-19 were found in patients with blood glucose levels ranging from 5.53 to 7.27 mmol/L (odds ratio [OR], 3.98; 95% confidence interval [CI], 1.81-8.75) and in patients with blood glucose ≥7.27 mmol/L (OR, 12.10; 95% CI, 5.53-26.48) than in those with blood glucose <5.53 mmol/L. There was a trend toward better survival in patients with blood glucose <5.53 mmol/L than in patients with blood glucose from 5.53 to 7.27 mmol/L (hazard ratio [HR], 6.34; 95% CI, 1.45-27.71) and ≥7.27 mmol/L (HR, 19.37; 95% CI, 4.68-80.17). Estimated 10-day overall survival rates were 96.8%, 90.6%, and 69.3% in patients with blood glucose <5.53 mmol/L, 5.53 to 7.27 mmol/L, and ³7.27 mmol/L, respectively. CONCLUSIONS Hyperglycemia was association with severity of COVID-19 pneumonia and with increased patient mortality. These findings support the need for blood glucose monitoring and control of hyperglycemia in patients with COVID-19 pneumonia.

Hyperglycaemia increases mortality risk in non-diabetic patients with COVID-19 even more than in diabetic patients.

AIM: Diabetes has been identified as a risk factor for poor outcomes in patients with COVID-19. We examined the association of hyperglycaemia, both in the presence and absence of pre-existing diabetes, with severity and outcomes in COVID-19 patients. METHODS: Data from 74,148 COVID-19-positive inpatients with at least one recorded glucose measurement during their inpatient episode were analysed for presence of pre-existing diabetes diagnosis and any glucose values in the hyperglycaemic range (>180 mg/dl). RESULTS: Among patients with and without a pre-existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70-180 mg/dl) in both groups (non-diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). When adjusting for patient age, BMI, severity on admission and oxygen saturation on admission, this increased risk of mortality persisted and varied by diabetes diagnosis. Among patients with a pre-existing diabetes diagnosis, any hyperglycaemic value during the episode was associated with a substantial increase in the odds of mortality (OR: 1.77, 95% CI: 1.52-2.07); among patients without a pre-existing diabetes diagnosis, this risk nearly doubled (OR: 3.07, 95% CI: 2.79-3.37). CONCLUSION: This retrospective analysis identified hyperglycaemia in COVID-19 patients as an independent risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. This indicates that the extent of glucose control could serve as a mechanism for modifying the risk of COVID-19 morality in the inpatient environment.

Association between Hb A1c and Severity of COVID-19 Patients.

This study aimed to examine the relationship between Hb A1c levels and the clinical course of coronavirus-19 (COVID-19) patients. Sixty-six COVID-19(+) patients with high Hb A1c and 46 with average Hb A1c and 30 COVID-19(-) patients with average Hb A1c were included. Hb A1c levels and parameters examined in COVID-19(+) patients were compared between groups, and correlation analysis was performed between these parameters and Hb A1c levels. The effect of Hb A1c levels on intensive care unit (ICU) admission and mortality rate in COVID-19 patients was analyzed with the χ2 test. It was observed that hemoglobin (Hb) and arterial oxygen saturation (SaO2) levels of the COVID-19 (+) groups was lower than the COVID-19 (-) group, while ferritin, D-dimer, procalcitonin (PCT), and C-reactive protein (CRP) levels were higher. The COVID-19 (+) group with high Hb A1c had higher lactate dehydrogenase (LDH), PCT and D-dimer levels than the other two groups, while Hb, partial arterial oxygen pressure (PaO2) levels were lower. The Hb A1c levels of the COVID-19 (+) groups were positively correlated with absolute neutrophil count (ANC), LDH, PCT and (K+) levels, while negatively correlated with Hb and PaO2 levels. Hb A1c was found to be associated with the inflammation process, coagulation disorders and low PaO2 in COVID-19 patients. The COVID-19 patients with high Hb A1c levels had a higher mortality rate than other COVID-19 patients. Using Hb A1c measurements with other prognostic markers would contribute to the patient's risk of death assessment.

Clinical Trials of COVID-19 Therapies Should Account for Diabetes and Hyperglycemia.

Complications of Coronavirus Disease 2019 (COVID-19) occur with increased frequency in people admitted to the hospital with diabetes or hyperglycemia. The increased risk for COVID-19 infections in the presence of these metabolic conditions is in part due to overlapping pathophysiologic features of COVID-19, diabetes, and glucose control. Various antiviral treatments are being tested in COVID-19 patients. We believe that in these trials, it will be useful to evaluate treatment effect differences in patients stratified according to whether they have diabetes or hyperglycemia. In this way, it will be possible to better facilitate development of antiviral treatments that are most specifically beneficial for the large subset of COVID-19 patients who have diabetes or hyperglycemia.

COVID-19 in a country with a very high prevalence of diabetes: The impact of admission hyperglycaemia on mortality.

Aims: To evaluate the frequency of diabetes and admission hyperglycaemia in Mexican COVID-19 patients, to describe the clinical and biochemical characteristics of patients with admission hyperglycaemia and to determinate the impact of diabetes and admission hyperglycaemia on COVID-19 severity and mortality. Methods: A multicentric study was performed in 480 hospitalized patients with COVID-19. Clinical and biochemical characteristics were evaluated in patients with admission hyperglycaemia and compared with non-hyperglycaemic patients. The effect of diabetes and admission hyperglycaemia on severity and risk of death were evaluated. Results: Age was 50.7 ± 13.6 years; 68.3% were male. Some 48.5% (n = 233) had admission hyperglycaemia; 29% (n = 139) of these patients had pre-existing diabetes. Patients with admission hyperglycaemia had more requirement of invasive mechanical ventilation (IMV), higher levels of urea, D-dimer and neutrophil-lymphocyte ratio (NLR), as well as lower lymphocyte count. An association between admission hyperglycaemia with IMV and D-dimer with glucose was found. Age ≥50 years (OR 2.09; 95%CI 1.37-3.17), pre-existing diabetes (OR 2.38; 95%CI 1.59-5.04) and admission hyperglycaemia (OR 8.24; 95%CI 4.74-14.32) were risk factors for mortality. Conclusions: Admission hyperglycaemia is presented in 48.5% of COVID-19 patients. Diabetes and admission hyperglycaemia are associated with the severity of disease and mortality. This study shows the devastating conjunction of hyperglycaemia and COVID-19. Clinical trial registration: Clinical characteristics of patients with COVID-19, DI/20/204/04/41 (Hospital General de Mexico) and NR-13-2020 (Hospital Regional de Alta Especialidad Ixtapaluca).

Association Between Longitudinal Change in Abnormal Fasting Blood Glucose Levels and Outcome of COVID-19 Patients Without Previous Diagnosis of Diabetes.

This retrospective study examined changes in fasting blood glucose (FBG) levels during hospitalization and their effect on risk of death for Coronavirus disease 2019 (COVID-19) patients without previously diagnosed diabetes. A model with low- and high-stable pattern trajectories was established based on a longitudinal change in FBG levels. We analyzed FBG trajectory-associated clinical features and risk factors for death due to COVID-19. Of the 230 enrolled patients, 44 died and 87.83% had a low-stable pattern (average FBG range: 6.63-7.54 mmol/L), and 12.17% had a high-stable pattern (average FBG range: 12.59-14.02 mmol/L). There were statistical differences in laboratory findings and case fatality between the two FBG patterns. Multivariable logistic regression analysis showed that increased neutrophil count (odds ratio [OR], 25.43; 95% confidence interval [CI]: 2.07, 313.03), elevated direct bilirubin (OR, 5.80; 95%CI: 1.72, 19.58), elevated creatinine (OR, 26.69; 95% CI: 5.82, 122.29), lymphopenia (OR, 8.07; 95% CI: 2.70, 24.14), and high-stable FBG pattern (OR, 8.79; 95% CI: 2.39, 32.29) were independent risk factors for higher case fatality in patients with COVID-19 and hyperglycemia but no history of diabetes. FBG trajectories were significantly associated with death risk in patients with COVID-19 and no diabetes.

The prognostic role of hyperglycemia and glucose variability in covid-related acute respiratory distress Syndrome.

AIMS: Due to heterogeneity on the prognostic role of glucose values and glucose variability in Novel Coronavirus (COVID) disease, we aimed at assessing the prognostic role for Intensive Care Unit (ICU) death of admission hyperglycaemia, peak glycemia and glucose variability in critically ill COVID patients: METHODS: 83 patients consecutively admitted for COVID-related Acute Respiratory Distress Syndrome (ARDS) from from 1st March to 1st October 2020. RESULTS: Non survivors were older, with more comorbidities and a more severe disease. Corticosteroids were used in the majority of patients (54/83, 65%) with no difference between survivors and non survivors. Mean blood glucose values, (during the first 24 and 48 h, respectively), were comparable between the two subgroups, as well as SD 24 and CV 24. During the first 48 h, survivors showed significantly lower values of SD 48 (p < 0.001) and CV 48, respectively (p < 0.001) than non survivors. CONCLUSIONS: in consecutive COVID-related ARDS patients admitted to ICU hyperglycemia (>180 mg/dl) is more common in non survivors who also showed a significantly higher glucose variability in the first 48 h since ICU admission. Our findings point to the clinical significance of in-ICU glucose control in severe COVID patients.

Association of hyperglycaemia with hospital mortality in nondiabetic COVID-19 patients: A cohort study.

OBJECTIVE: Diabetes is a known risk factor for mortality in Coronavirus disease 2019 (COVID-19) patients. Our objective was to identify prevalence of hyperglycaemia in COVID-19 patients with and without prior diabetes and quantify its association with COVID-19 disease course. RESEARCH DESIGN AND METHODS: This observational cohort study included all consecutive COVID-19 patients admitted to John H Stroger Jr. Hospital, Chicago, IL from March 15, 2020 to May 3, 2020 and followed till May 15, 2020. The primary outcome was hospital mortality, and the studied predictor was hyperglycaemia [any blood glucose ≥7.78 mmol/L (140 mg/dL) during hospitalization]. RESULTS: Of the 403 COVID-19 patients studied, 51 (12.7%) died; 335 (83.1%) were discharged while 17 (4%) were still in hospital. Hyperglycaemia occurred in 228 (56.6%) patients; 83 of these hyperglycaemic patients (36.4%) had no prior history of diabetes. Compared to the reference group no-diabetes/no-hyperglycaemia patients the no-diabetes/hyperglycaemia patients showed higher mortality [1.8% versus 20.5%, adjusted odds ratio 21.94 (95% confidence interval 4.04-119.0), P < 0.001]; improved prediction of death (P = 0.01) and faster progression to death (P < 0.01). Hyperglycaemia within the first 24 and 48 h was also significantly associated with mortality (odds ratio 2.15 and 3.31, respectively). CONCLUSIONS: Hyperglycaemia without prior diabetes was common (20.6% of hospitalized COVID-19 patients) and was associated with an increased risk of and faster progression to death. Development of hyperglycaemia in COVID-19 patients who do not have diabetes is an early indicator of progressive disease.

Immunological Characteristics in Type 2 Diabetes Mellitus Among COVID-19 Patients.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634. Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear. Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients. Design and Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups. Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors. Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.

Hyperglycemia and Correlated High Levels of Inflammation Have a Positive Relationship with the Severity of Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. METHODS: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). RESULTS: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes (n = 366), patients with diabetes (n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. CONCLUSION: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.

Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies.

Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)-OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.