SARS-CoV-2 Infection Related Hyperglycemia during hospitalization and three months post-discharge (preprint)

Hyperglycemia or diabetes mellitus during COVID-19 has always been a great concern and heralds severe forms of the disease, we also don’t know whether this condition will continue as diabetes mellitus even after convalescence. For this purpose we conducted a study to investigate this condition and factors related to it in hospitalized patients and even three months post-discharge we followed them up. We gathered data from 202 patients that fulfilled our inclusion criteria, among them 100 patients were hyperglycemic. Patients in hyperglycemic status experienced significantly longer duration of hospitalization than normoglycemic patients and significantly showed more severe forms of the disease. During their follow up three months post-discharge for the investigation of glycemic status, 46 out of 97 patients were diagnosed with diabetes mellitus and have been taking anti-diabetic drugs while 29 patients only had normal glycemic status.

Hyperglycemia-induced cathepsin L maturation: Implications for diabetic comorbidities and COVID-19 susceptibility (preprint)

Diabetes is the second most frequent chronic comorbidity for COVID-19 mortality, yet the underlying mechanism remains unclear. Previous studies suggest that Cathepsin L (CTSL) is implicated in diabetic complications such as nephropathy and retinopathy. Our previous research identified CTSL as a critical protease that promotes SARS-CoV-2 infection and a potential drug target. Here, we show that individuals with diabetes have elevated blood CTSL levels, which facilitates SARS-CoV-2 infection. Chronic hyperglycemia, as indicated by HbA1c levels, is positively correlated with CTSL concentration and activity in diabetic patients. Acute hyperglycemia induced by a hyperglycemic clamp in healthy individuals increases CTSL activity. In vitro, high glucose, but not high insulin, promotes SARS-CoV-2 infection in wild-type (WT) cells, while CTSL knockout (KO) cells show reduced susceptibility to high glucose-promoted effects. Using lung tissue samples from diabetic and non-diabetic patients, as well as db/db diabetic and control mice, our findings demonstrate that diabetic conditions increase CTSL activity in both humans and mice. Mechanistically, high glucose levels promote CTSL maturation and CTSL translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. This study emphasizes the significance of hyperglycemia-induced cathepsin L maturation in the development of diabetic comorbidities and complications.

Immune Correlates of Hyperglycemia and Vaccination in a Non-human Primate Model of Long-COVID (preprint)

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are major manifestations of the post-acute sequelae of SARS-CoV-2 (PASC). Our understanding of lasting glucometabolic disruptions after acute COVID-19 remains unclear due to the lack of animal models for metabolic PASC. Here, we report a non-human primate model of metabolic PASC using SARS-CoV-2 infected African green monkeys (AGMs). Using this model, we have identified a dysregulated chemokine signature and hypersensitive T cell population during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. This persistent hyperglycemia correlates with elevated hepatic glycogen, but there was no evidence of long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the AGM metabolic PASC model exhibits important similarities to human metabolic PASC and can be utilized to assess therapeutic candidates to combat this syndrome.

Type1 Diabetes and COVID-19: A Systematic Review and Possible Management (preprint)

Introduction SARS-CoV-2 infection normally damages respiratory system but may likewise impair endocrine organs’ function. Thyroid dysfunction and hyperglycemia are common endocrine complications of SARS-CoV-2 infection. Onset of T1D and associated complications including DKA, hospitalization and death, are thought to be increased during the COVID-19 pandemic. The aim of this study is to review the available data about the incidence rate of T1D and accompanying complications since the beginning of the COVID-19 pandemic. Methods: A systematic review was conducted using electronic databases PubMed and Google Scholar. The keywords “T1D, T1DM, Type 1 DM or Type 1 Diabetes”, “Coronavirus, SARS-CoV-2 or COVID-19” were used to search these databases. Titles and abstracts were screened for selection, and then relevant studies were reviewed in full text. Result: we selected 21 manuscripts out of 296 identified studies. Data about the incidence rate of T1D, hospitalization and death are not consistent across countries, but DKA incidence and severity seem to be higher during the COVID-19 pandemic. Conclusion: Our data collection demonstrated that COVID-19 may or may not increase the incidence of type 1 diabetes. Nevertheless, it is associated with higher incidence and severity of DKA in T1D patients. Antivirals are not fully protective against endocrine complications of SARS-CoV-2 infection. Combining medications that reduce SARS-CoV-2 entry into the cells and modulate the immune response to infection is an alternative practical approach to treating COVID-19.

Mild Hyperglycaemia in Hospitalised Children with Moderate COVID-19 Infection.

Background and Objectives: COVID-19 infection may influence many physiological processes, including glucose metabolism. Acute hyperglycaemia has been related to a worse prognosis in patients with severe COVID-19 infection. The aim of our study was to find out if moderate COVID-19 infection is associated with hyperglycaemia. Materials and Methods: A total of 235 children were enrolled in the study between October 2021 and October 2022, 112 with confirmed COVID-19 infection and 123 with other RNA viral infection. In all patients, types of symptoms, glycaemia at the time of admission, and basic anthropometric and biochemical parameters were recorded. Results: Average glycaemia was significantly higher in COVID-19 patients compared to other viral infections (5.7 ± 1.12 vs. 5.31 ± 1.4 mmol/L, p = 0.011). This difference was more obvious in subgroups with gastrointestinal manifestations (5.6 ± 1.11 vs. 4.81 ± 1.38 mmol/L, p = 0.0006) and with fever (5.76±1.22 vs. 5.11±1.37 mmol/L, p = 0.002), while no significant difference was found in subgroups with mainly respiratory symptoms. The risk of hyperglycaemia (>5.6 mmol/L) was higher in COVID-19 patients compared to other viral infections (OR = 1.86, 95%CI = 1.10-3.14, p = 0.02). The risk of hyperglycaemia was significantly higher in COVID-19 compared to other viral infections in the subgroups of patients with fever (OR = 3.59, 95% CI 1.755-7.345, p = 0.0005) and with gastrointestinal manifestations (OR = 2.48, 95% CI 1.058-5.791, p = 0.036). Conclusion: According to our results, mild hyperglycaemia was significantly more common in children with moderate COVID-19 infection compared to other RNA virus respiratory and gastrointestinal infections, especially when accompanied by fever or gastrointestinal symptoms.

Increased risk of new-onset diabetes in patients with COVID-19: a systematic review and meta-analysis.

Background: There is growing evidence that patients with COVID-19 are at increased risk of new-onset diabetes. The limited preliminary studies do not provide strong evidence. To assess the association of the SARS-CoV-2 virus with new-onset diabetes and to characterize the population. Methods: Search PubMed, Embase, Cochrane Library, and Web of Science electronic databases for a limited period from December 2019 to July 2022. Two independent reviewers conducted a thorough review of eligible articles and extracted relevant information. Pooled proportions, risk ratios (RR), and 95% confidence intervals (95% CI) indicated the incidence and risk ratios of events. Results: The incidence of new-onset diabetes and hyperglycemia in patients with COVID-19 was 5% (P < 0.001) (3 and 30% for new-onset diabetes and hyperglycemia, respectively), with age, ethnicity, time of diagnosis, and study type all having an impact on the incidence (P < 0.05). New-onset diabetes and hyperglycemia were 1.75 times higher in COVID-19 patients than in non-COVID-19 patients. In new-onset diabetes and hyperglycemia population, the percentage of men is 60% (40% for women), with a mortality rate of 17%. The proportion of new-onset diabetes and hyperglycemia after infection with COVID-19 was 25% in men and 14% in women. Conclusions: The incidence and relative risk of new-onset diabetes and hyperglycemia are elevated after COVID-19 infection, especially in the early COVID-19 and male populations. Systemic review registration: PROSPERO registration no.: CRD42022382989 https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=382989.

Ramadan fasting in people with diabetes and chronic kidney disease (CKD) during the COVID-19 pandemic: The DaR global survey.

BACKGROUND AND AIMS: The DaR Global survey was conducted to observe the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in people with diabetes and chronic kidney disease (CKD). METHODS: Muslim people with diabetes and CKD were surveyed in 13 countries shortly after the end of Ramadan 2020, using a simple Survey Monkey questionnaire. RESULTS: This survey recruited 6736 people with diabetes, of which 707 (10.49%) had CKD. There were 118 (16.69%) people with type1 diabetes (T1D), and 589 (83.31%) were with type2 diabetes (T2D). 62 (65.24%) people with T1D and 448 (76.06%) people with T2D had fasted with CKD. Episodes of hypoglycaemia and hyperglycaemia were more frequent among people with T1D compared to T2D, 64.52% and 43.54% vs 25.22% and 22.32% respectively. Visits to the emergency department and hospitalization were more frequent among people with CKD, however no significant difference was found between people with T1D and T2D. CONCLUSION: The COVID-19 pandemic had only a minor effect on the intention to fast during Ramadan in people with diabetes and CKD. However, hypoglycaemia and hyperglycaemia were found to be more frequent, as well as emergency visits and hospital admissions among people with diabetic kidney disease. Prospective studies are needed in future to evaluate the risk indicators of hypoglycaemia and hyperglycaemia among fasting people with CKD, especially in the context of different stages of kidney disease.

[The impact of carbohydrate metabolism disorders on the early and long-term clinical outcomes of patients with COVID-19 according to the AKTIV and AKTIV 2 registries].

BACKGROUND: Numerous studies indicate a high incidence of various disorders of carbohydrate metabolism against the new coronavirus infection. These disorders aggravate the course of infection and increase mortality. Thereby, analysis of risk factors for unfavorable outcomes and assessment of the long-term consequences of COVID-19 in patients with impaired carbohydrate metabolism is of great importance. AIM: To investigate the association between carbohydrate metabolism disorders in COVID-19 patients and mortality, course of infection, long-term consequences, as well as to identify risk factors for an unfavorable disease course. MATERIALS AND METHODS: A retrospective analysis of data from the combined multicenter non-interventional real-world AKTIV and AKTIV 2 registries was performed. The sample included 9290 patients who had COVID-19 with varying severity from June 29, 2020, to November 29, 2020 (AKTIV) and from October 01, 2020, to March 30, 2021 (AKTIV 2). The patients were divided into 3 groups: Group 1 - patients with intact carbohydrate metabolism, n=6606; Group 2 - patients with newly diagnosed hyperglycemia (NDH), n=1073; Group 3 - patients with a history of type 2 diabetes mellitus (DM2), n=1611. The groups were assessed for clinical and laboratory parameters, comorbidities, mortality, carbohydrate metabolic status, and well-being during the infection and at 12 months. RESULTS: The prevalence of carbohydrate metabolism disorders (CMD) was 28,9%, with DM2 patients accounting for 17,3% and patients with newly diagnosed hyperglycemia (NDH) for 11,6%. The mortality rate of patients with hyperglycemia of any origin was 10.6%, which was significantly higher compared to patients without hyperglycemia (3,9%). The probability of lethal outcome increased 2,48-fold in the group of patients with DM2 and 2,04-fold in the group of patients with NDH. At the same time, the probability of a lethal outcome decreased 2,94-fold in patients without CMD. At 12 months, patients with CMD showed a significantly higher frequency and longer persistence of complaints. This trend was more pronounced in patients with DM2 than in those with NDH. Only 1,7% of patients from the NDH group had type 2 diabetes and were receiving oral hypoglycemic medications one year after the infection. A prognostic model was developed to determine the risk of lethal outcome. The model included such known predictors as concomitant ischemic heart disease, history of myocardial infarction or stroke, blood glucose level, and age. CONCLUSION: Carbohydrate metabolism disorders aggravate the course of COVID-19 and increase mortality. One year after infection, patients with DM2 and NDH were more likely to have symptoms typical for post-COVID syndrome, and NDH resolved in most cases after the infection.

Dysglycemias in patients admitted to ICUs with severe acute respiratory syndrome due to COVID-19 versus other causes - a cohort study.

BACKGROUND: Dysglycemias have been associated with worse prognosis in critically ill patients with COVID-19, but data on the association of dysglycemia with COVID-19 in comparison with other forms of severe acute respiratory syndrome are lacking. This study aimed to compare the occurrence of different glycemic abnormalities in patients with severe acute respiratory syndrome and COVID-19 admitted to intensive care units versus glycemic abnormalities in patients with severe acute respiratory syndrome from other causes, to evaluate the adjusted attributable risk associated with COVID-19 and dysglycemia and to assess the influence of these dysglycemias on mortality. METHODS: We conducted a retrospective cohort of consecutive patients with severe acute respiratory syndrome and suspected COVID-19 hospitalized in intensive care units between March 11 and September 13, 2020, across eight hospitals in Curitiba-Brazil. The primary outcome was the influence of COVID-19 on the variation of the following parameters of dysglycemia: highest glucose level at admission, mean and highest glucose levels during ICU stay, mean glucose variability, percentage of days with hyperglycemia, and hypoglycemia during ICU stay. The secondary outcome was the influence of COVID-19 and each of the six parameters of dysglycemia on hospital mortality within 30 days from ICU admission. RESULTS: The sample consisted of 841 patients, of whom 703 with and 138 without COVID-19. Comparing patients with and without COVID-19, those with COVID-19 had significantly higher glucose peaks at admission (165 mg/dL vs. 146 mg/dL; p = 0.002) and during ICU stay (242 mg/dL vs. 187md/dL; p < 0.001); higher mean daily glucose (149.7 mg/dL vs. 132.6 mg/dL; p < 0.001); higher percentage of days with hyperglycemia during ICU stay (42.9% vs. 11.1%; p < 0.001); and greater mean glucose variability (28.1 mg/dL vs. 25.0 mg/dL; p = 0.013). However, these associations were no longer statistically significant after adjustment for Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, and C-reactive protein level, corticosteroid use and nosocomial infection. Dysglycemia and COVID-19 were each independent risk factors for mortality. The occurrence of hypoglycemia (< 70 mg/dL) during ICU stay was not associated with COVID-19. CONCLUSION: Patients with severe acute respiratory syndrome due to COVID-19 had higher mortality and more frequent dysglycemia than patients with severe acute respiratory syndrome due to other causes. However, this association did not seem to be directly related to the SARS-CoV-2 infection.

Diabetes, COVID-19, and questions unsolved.

Recent evidence suggests a role for Diabetes Mellitus in adverse outcomes from COVID-19 infection; yet the underlying mechanisms are not clear. Moreover, attention has turned to prophylactic vaccination to protect the population from COVID-19-related illness and mortality. We performed a comprehensive peer-reviewed literature search on an array of key terms concerning diabetes and COVID-19 seeking to address the following questions: 1. What role does diabetes play as an accelerator for adverse outcomes in COVID-19?; 2. What mechanisms underlie the differences in outcomes seen in people with diabetes?; 3. Are vaccines against COVID-19 efficacious in people with diabetes? The current literature demonstrates that diabetes is associated with an increased risk of adverse outcomes from COVID-19 infection, and post-COVID sequelae. Potential mechanisms include dysregulation of Angiotensin Converting Enzyme 2, Furin, CD147, and impaired immune cell responses. Hyperglycaemia is a key exacerbator of these mechanisms. Limited studies are available on COVID-19 vaccination in people with diabetes; however, the current literature suggests that vaccination is protective against adverse outcomes for this population. In summary, people with diabetes are a high-risk group that should be prioritised in vaccination efforts. Glycaemic optimisation is paramount to protecting this group from COVID-19-associated risk. Unsolved questions remain as to the molecular mechanisms underlying the adverse outcomes seen in people with diabetes; the functional impact of post-COVID symptoms on people with diabetes, their persistence, and management; how long-term vaccine efficacy is affected by diabetes, and the antibody levels that confer protection from adverse outcomes in COVID-19.

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Maternal glucose levels and future risk of developing cardiovascular disease: a systematic review and meta-analysis protocol.

INTRODUCTION: Hyperglycaemia during pregnancy has been considered as one of the risk factors for cardiovascular diseases (CVDs) among women. Although the evidence regarding the association between gestational diabetes mellitus (GDM) and subsequent CVD has been synthesised, there are no systematic reviews covering the evidence of the association among the non-GDM population. This systematic review and meta-analysis, therefore, aim to fill the gap by summarising existing evidence on the association between maternal glucose levels and the risk of future CVD in pregnant women with or without a diagnosis of GDM. METHODS AND ANALYSIS: This systematic review protocol was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. Comprehensive literature searches were performed in the following electronic databases: MEDLINE, EMBASE and CINAHL to identify relevant papers from inception to 31 December 2022. All observational studies (case-control studies, cohort studies and cross-sectional studies) will be included. Two reviewers will perform the abstract and full-text screening based on the eligibility criteria through Covidence. The Newcastle-Ottawa Scale will be used to assess the methodological quality of included studies. Statistical heterogeneity will be assessed by using the I2 test and Cochrane's Q test. If the included studies are found to be homogeneous, pooled estimates will be calculated and meta-analysis will be performed using Review Manager 5 (RevMan) software. Random effects will be used to determine weights for meta-analysis, if needed. Pre-specified subgroup analysis and sensitivity analysis will be performed, if needed. The study results will be presented in the sequence of main outcomes, secondary outcomes and important subgroup analysis for each type of glucose level separately. ETHICS AND DISSEMINATION: Given no original data will be collected, ethics approval is not applicable for this review. The results of this review will be disseminated by publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42022363037.

Dichotomising the risk of hyperglycaemia into diabetes and prediabetes may render a disservice to patient care.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for one-third of global mortality. Prediabetes increases the risk of CVDs as well as several other conditions, yet people with prediabetes may not seek intervention, thinking that they do not have diabetes, as the risk of progression may have not been emphasised by the healthcare professional. Accumulating evidence indicates that hyperglycaemia represents a continuum of CVD risk and dichotomising the risk into type 2 diabetes and prediabetes may deter early clinical intervention. It is proffered that the term 'prediabetes' is a misnomer that may disguise a serious condition, fostering complacency and undermining its prognostic significance.

A Clinical Update on Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) traditionally refers to abnormal glucose tolerance with onset or first recognition during pregnancy. GDM has long been associated with obstetric and neonatal complications primarily relating to higher infant birthweight and is increasingly recognized as a risk factor for future maternal and offspring cardiometabolic disease. The prevalence of GDM continues to rise internationally due to epidemiological factors including the increase in background rates of obesity in women of reproductive age and rising maternal age and the implementation of the revised International Association of the Diabetes and Pregnancy Study Groups' criteria and diagnostic procedures for GDM. The current lack of international consensus for the diagnosis of GDM reflects its complex historical evolution and pragmatic antenatal resource considerations given GDM is now 1 of the most common complications of pregnancy. Regardless, the contemporary clinical approach to GDM should be informed not only by its short-term complications but also by its longer term prognosis. Recent data demonstrate the effect of early in utero exposure to maternal hyperglycemia, with evidence for fetal overgrowth present prior to the traditional diagnosis of GDM from 24 weeks' gestation, as well as the durable adverse impact of maternal hyperglycemia on child and adolescent metabolism. The major contribution of GDM to the global epidemic of intergenerational cardiometabolic disease highlights the importance of identifying GDM as an early risk factor for type 2 diabetes and cardiovascular disease, broadening the prevailing clinical approach to address longer term maternal and offspring complications following a diagnosis of GDM.

COVID-19 and Diabetes.

The prevalence of diabetes in people with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has varied worldwide. Most of the available evidence suggests a significant increase in severity and mortality of COVID-19 in people with either type 1 (T1DM) or type 2 diabetes mellitus (T2DM), especially in association with poor glycemic control. While new-onset hyperglycemia and new-onset diabetes (both T1DM and T2DM) have been increasingly recognized in the context of COVID-19 and have been associated with worse outcome, no conclusive evidence yet suggests direct tropism of SARS-CoV-2 on the ß cells of pancreatic islets. While all approved oral antidiabetic agents appear to be safe in people with T2DM having COVID-19, no conclusive data are yet available to indicate a mortality benefit with any class of these drugs, in the absence of large randomized controlled trials.

Continuous Glucose Monitoring in the Intensive Care Unit.

Traditionally, the care of critically ill patients with diabetes or stress hyperglycemia in the intensive care unit (ICU) demands the use of continuous intravenous insulin (CII) therapy to achieve narrow glycemic targets. To reduce the risk of iatrogenic hypoglycemia and to achieve glycemic targets during CII, healthcare providers (HCP) rely on hourly point-of-care (POC) arterial or capillary glucose tests obtained with glucose monitors. The burden of this approach, however, was evident during the beginning of the pandemic when the immediate reduction in close contact interactions between HCP and patients with COVID-19 was necessary to avoid potentially life-threatening exposures. Taking advantage of the advancements in current diabetes technologies, including continuous glucose monitoring (CGM) devices integrated with digital health tools for remote monitoring, HCP implemented novel protocols in the ICU to care for patients with COVID-19 and hyperglycemia. We provide an overview of research conducted in the ICU setting with the use of initial CGM technology to current devices and summarize our recent experience in the ICU.

Case report: Fulminant type 1 diabetes following paucisymptomatic SARS-CoV-2 infection during late pregnancy.

Background: Dysregulation of glucose metabolism has been linked to SARS-CoV-2 infection. In addition, the occurrence of new onset diabetes mellitus, including fulminant type 1 diabetes, has been reported after SARS-CoV-2 infection or vaccination. Methods and results: A young Chinese woman in her last trimester of pregnancy presented with an abrupt progression of hyperglycemia and ketoacidosis, but with a near-normal glycohemoglobin level following paucisymptomatic SARS-CoV-2 infection. The low C peptide levels, both fasting and postprandial, reflected profound insulin deficiency in the setting of negative islet autoantibody testing, consistent with a diagnosis of fulminant type 1 diabetes. Ketoacidosis and hyperglycemia quickly improved following the introduction of insulin therapy, but not the ß cell function. The patient received treatment with insulin pump therapy after being discharged, and the first follow-up revealed a well-controlled glucose profile. Conclusions: New-onset FT1D can occur after SARS-CoV-2 infection. Our report raises awareness of this rare but serious situation, promoting early recognition and management of FT1D during the COVID-19 pandemic.

SARS-CoV-2 Infection Causes Hyperglycemia in Cats.

Isolated reports of new-onset diabetes in patients with coronavirus disease 2019 (COVID-19) have led researchers to hypothesize that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human exocrine and endocrine pancreatic cells ex vivo and in vivo. However, existing research lacks experimental evidence indicating that SARS-CoV-2 can infect pancreatic tissue. Here, we found that cats infected with a high dose of SARS-CoV-2 exhibited hyperglycemia. We also detected SARS-CoV-2 RNA in pancreatic tissues of these cats, and immunohistochemical staining revealed the presence of SARS-CoV-2 nucleocapsid protein (NP) in islet cells. SARS-CoV-2 NP and spike proteins were primarily detected in glucagon-positive cells, and most glucagon-positive cells expressed ACE2. Additionally, immune protection experiments conducted on cats showed that blood glucose levels of immunized cats did not increase postchallenge. Our data indicate cat pancreas as a SARS-CoV-2 target and suggest that the infection of glucagon-positive cells could contribute to the metabolic dysregulation observed in SARS-CoV-2-infected cats.

Glucose variability is a marker for COVID-19 severity and mortality.

Objective: We aimed to investigate the association between glucose coefficient of variation (CV) and mortality and disease severity in hospitalized patients with coronavirus disease-19 (COVID-19). Subjects and Methods: Retrospective cohort study in a tertiary center of patients with COVID-19 admitted to designated departments between March 11th, 2020, and November 2nd, 2020. We divided patients based on quartiles of glucose CV after stratification to those with and without diabetes mellitus (DM). Main outcomes were length of stay and in-hospital mortality. Results: The cohort included 565 patients with a mean age of 67.71 ± 15.45 years, and 62.3% were male. Of the entire cohort, 44.4% had DM. The median glucose CV was 32.8% and 20.5% in patients with and without DM, respectively. In patients with DM, higher glucose CV was associated with a longer hospitalization in the unadjusted model (OR = 2.7, 95% CI [1.3,5.6] for Q4), and when adjusted for age, sex, comorbidities, and laboratory markers, this association was no longer statistically significant (OR = 1.3, 95% CI [0.4,4.5] for Q4). In patients with and without DM, higher glucose CV was associated with higher rates of in-hospital mortality in the unadjusted model, but adjustment for comorbidities and laboratory markers eliminated the association (OR = 0.5, 95% CI [0.1,3.4] for Q4 in patients with DM). Conclusion: Higher glucose CV was associated with increased in-hospital mortality and length of stay, but this association disappeared when the adjustment included laboratory result data. Glucose CV can serve as a simple and cheap marker for mortality and severity of disease in patients with COVID-19.