Background and Objectives: Bulgaria had the highest mortality rate of COVID-19 in Europe and the second highest in the world based on statistical data. This study aimed to determine the mortality predictors in 306 adult patients with COVID-19 infection, treated at the COVID-19 Ward of St. George University Hospital in Plovdiv, Bulgaria in the period of August 2021-April 2022. Materials and Methods: All admitted and treated patients had a positive PCR test for SARS-CoV-2. They were assigned in three groups based on the severity rating scale published in NIH COVID-19 Treatment Guidelines by Stat Pearls Publishing, 2022. Demographic, clinical, and laboratory parameters and pre-existing comorbidities were investigated. Parametric and non-parametric methods were used for statistics. Logistic regression was applied for parameters significantly associated with mortality. Results: Data showed that demographic indicators were not significantly associated with poorer outcome. Among comorbidities, cardiovascular, chronic pulmonary and endocrine disorders were found to be related to poor survival rates (p = 0.003, p = 0.003 and p = 0.017 resp.) Clinical symptoms, such as sore throat, dry or productive cough and breathlessness, were determinants of poor outcome (p = 0.027, p = 0.029, p = 0.004 and p = 0.002 resp.). Laboratory parameters linked to mortality were elevated d-dimers (p = 0.015), ferritin (p = 0.009) and creatinine (p = 0.038). p02 < 50 and saturation < 90 also indicated a higher risk of death (p = 0.006 and p = 0021). Conclusions: Logistic regression showed that each stage of disease severity increased the risk of death 3.6 times, chronic pulmonary disorders increased it by 4.1, endocrine by 2.4 and dyspnea by 3.1 times.

Background Despite being typically a viral respiratory disease, COVID-19 has harmful effects that go beyond the respiratory system. The endocrine system is particularly susceptible to damage due to the high expression of angiotensin-converting enzyme-2 receptors. This study evaluates glycemic status in survivors of COVID-19. Methodology In this prospective, observational study, 96 individuals were enrolled from the COVID-19 unit of Bangabandhu Sheikh Mujib Medical University (BSMMU). Mild and moderate COVID-19 patients were classified as non-severe, whereas severe and critical cases were classified as severe, following the WHO disease severity classification. Follow-ups were conducted at the post-COVID-19 clinic at BSMMU one and six months after diagnosis. Blood samples for fasting blood sugar and glycated hemoglobin measurements were collected within 24 hours of initial diagnosis and during each follow-up at the first and sixth months. Results Of the 96 participants, the non-severe and severe groups consisted of 49 (51%) and 47 (49%) participants, respectively. Among the participants, 62 (63.9%) were men, the mean age was 54.2 (15.9) years, and hypertension was the most common comorbidity (37, 38.5%). After six months, 12 new cases of diabetes (15.4%) were observed, with a male predominance (10, 62%). After adjusting for potential confounders, we found that severe COVID-19 was substantially linked to a higher risk of diabetes at six months (odds ratio = 5.5, 95% confidence interval, 1.1-27.7, p = 0.03). Conclusions The study findings showed a significant association between a higher frequency of diabetes and severe COVID-19.

Background and Objectives: We conducted a retrospective observational study to evaluate the impact of elevated blood glucose levels in patients with SARS-CoV-2 infection and a prior diagnosis of diabetes mellitus (DM) or newly diagnosed hyperglycemia. Materials and Methods: This study analyzed 6065 patients admitted to the COVID-19 departments of the "Marius Nasta" National Institute of Pulmonology in Bucharest, Romania, between 26 October 2020 and 5 January 2023. Of these, 813 patients (13.40%) were selected for analysis due to either a pre-existing diagnosis of DM or hyperglycemia at the time of hospital admission. Results: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated in patients with blood glucose levels exceeding 300 mg/dL. These elevations correlated with the presence of respiratory failure and increased mortality rates. Additionally, oxygen requirements were significantly higher at elevated blood glucose levels (p < 0.001), with a direct relationship between glycemia and oxygen demand. This was accompanied by lower oxygen saturation levels (p < 0.001). Maximum blood glucose levels were associated with the severity of respiratory failure (AUC 0.6, 95% CI: 0.56-0.63, p < 0.001). We identified cut-off values for blood glucose at admission (217.5 mg/dL) and maximum blood glucose during hospitalization (257.5 mg/dL), both of which were associated with disease severity and identified as risk factors for increased mortality. Conclusions: High blood glucose levels, both at admission and during hospitalization, were identified as risk factors for poor prognosis and increased mortality in patients with SARS-CoV-2 infection, regardless of whether the hyperglycemia was due to a prior diagnosis of DM or was newly developed during the hospital stay. These findings underscore the importance of glycemic control in the management of hospitalized COVID-19 patients.

Although COVID-19 initially caused great concern about respiratory symptoms, mounting evidence shows that also the pancreas is productively infected by SARS-CoV-2. However, the severity of pancreatic SARS-CoV-2 infection and its pathophysiology is still under debate. Here, we investigate the consequences of SARS-CoV-2 pancreatic infection and the role of the host factor Placenta-associated protein (PLAC8).

We analyze plasma levels of pancreatic enzymes and inflammatory markers in a retrospective cohort study of 120 COVID-19 patients distributed in 3 severity-stratified groups. We study the expression of SARS-CoV-2 and PLAC8 in the pancreas of deceased COVID-19 patients as well as in non-infected donors. We perform pseudovirus infection experiments in PLAC8 knock-out PDAC and human beta cell-derived cell lines and validate results with SARS-CoV-2 virus.

We find that analysis of circulating pancreatic enzymes aid the stratification of patients according to COVID-19 severity and predicts outcomes. Interestingly, we find an association between PLAC8 expression and SARS-CoV-2 infection in postmortem analysis of COVID-19 patients both in the pancreas and in other bonafide SARS-CoV-2 target tissues. Functional experiments demonstrate the requirement of PLAC8 in SARS-CoV-2 pancreatic productive infection by pseudovirus and full SARS-CoV-2 infectious virus inoculum from Wuhan-1 and BA.1 strains. Finally, we observe an overlap between PLAC8 and SARS-CoV-2 immunoreactivities in the pancreas of deceased patients.

Our data indicate the human pancreas as a SARS-CoV-2 target with plausible signs of injury and demonstrate that the host factor PLAC8 is required for SARS-CoV-2 pancreatic infection, thus defining new target opportunities for COVID-19-associated pancreatic pathogenesis.

The world is currently grappling with the potentially life-threatening coronavirus disease 2019 (COVID-19), marking it as the most severe health crisis in the modern era. COVID-19 has led to a pandemic, with the World Health Organization (WHO) predicting that individuals with diabetes are at a higher risk of contracting the virus compared to the general population. This review aims to provide a practical summary of the long-term impacts of COVID-19 on patients with diabetes. Specifically, it focuses on the effects of SARS-CoV-2 on different types of diabetic patients, the associated mortality rate, the underlying mechanisms, related complications, and the role of vitamin D and zinc in therapeutic and preventive approaches.

Relevant literature was identified through searches on PubMed, Web of Science, and Science Direct in English, up to April 2023.

COVID-19 can lead to distressing symptoms and pose a significant challenge for individuals living with diabetes. Older individuals and those with pre-existing conditions such as diabetes, coronary illness, and asthma are more susceptible to COVID-19 infection. Managing COVID-19 in individuals with diabetes presents challenges, as it not only complicates the fight against the infection but also potentially prolongs the recovery time. Moreover, the virus may thrive in individuals with high blood glucose levels. Various therapeutic approaches, including antidiabetic drugs, are available to help prevent COVID-19 in diabetic patients.

Diabetes increases the morbidity and mortality risk for patients with COVID-19. Efforts are globally underway to explore therapeutic interventions aimed at reducing the impact of diabetes on COVID-19.

Cardiovascular involvement in Multisystem Inflammatory Syndrome in Children (MIS-C), a potential consequence of coronavirus disease-2019 (COVID-19), is common. Conventional transthoracic echocardiography (TTE) provides primary data on the function of the left and right ventricles, while Speckle Tracking Echocardiography (STE) is more sensitive. This study aims to assess longitudinal cardiac function using STE in these patients. This longitudinal study was conducted from late 2021 to early 2022 at Imam Hossein Children's Hospital, Isfahan. Cardiac function was assessed by STE at the time of diagnosis and again two months later. Demographics, clinical characteristics, ECG interpretations, imaging studies, and serum cardiac marker levels were collected. Thirty-five pediatric patients with a mean age of 5.1 years (range: 4 months to 17 years) were included and prospectively followed. Twenty-nine of them, comprising 14 males (48.3%) and 15 females (51.7%), underwent STE and were compared with 29 healthy age- and sex-matched children. Factors related to adverse events included reduced myocardial function, enlarged left atrium or ventricle, and mitral regurgitation (MR). Patients with comorbidities affecting strain measurements were excluded from the strain analyses. A significant difference was observed between the groups in regional strains in the basal and apical septal and middle lateral regions. Global strain rate (GLS) and strain rates were not significantly different but were still lower than the control group. Twenty percent of patients had abnormal GLS but normal left ventricular ejection fraction (LVEF). All patients exhibited reduced segmental myocardial strain in at least one segment. Four out of 26 recovered patients without comorbidities had abnormal GLS at follow-up, despite normal LVEF. STE proves more useful than conventional echocardiography in patients with MIS-C, revealing subclinical cardiac injury in the acute and post-acute phases.

Diabetes mellitus (DM) is recognized and classified as a group of conditions marked by persistent high blood glucose levels. It is also an inflammatory condition that may influence concurrent disease states, including Coronavirus Disease 2019 (COVID-19). Currently, no effective drug has been found to treat COVID-19, especially in DM patients. Many herbal medicines, such as the well-known Andrographis paniculata, have been explored as drugs and complementary therapies due to their antidiabetic, antibacterial, antiviral, anti-inflammatory, and immunomodulatory effects. This study aimed to examine the potential of herbal medicines as complementary therapy in DM patients with COVID-19 complications, drawing from in-vitro and in-vivo investigations. This study analyzed articles published within the last 15 years using keywords including "herbal medicines", "COVID-19", "Diabetes Mellitus", "antidiabetics", "antiviral", and "anti-inflammatory". The results showed that several herbal medicines could serve as complementary therapy for DM patients with COVID-19 complications. These include Andrographis paniculata, Ageratum conyzoides, Artocarpus altilis, Centella asiatica, Momordica charantia, Persea gratissima, Phyllanthus urinaria, Physalis angulata, Tinospora cordifolia, and Zingiber zerumbet. Herbal medicines may serve as a complementary therapy for DM patients with COVID-19, but these claims need experimental validation in infection models and among affected patients.

Recent studies have found that a link between people with type 1 diabetes mellitus (T1DM) are at higher risk of morbidity as well as mortality from COVID-19 infection, indicating a need for vaccination. T1DM appears to impair innate and adaptive immunity. The overabundance of pro-inflammatory cytokines produced in COVID-19 illness that is severe and potentially fatal is known as a "cytokine storm." Numerous cohorts have revealed chronic inflammation as a key risk factor for unfavorable COVID-19 outcomes. TNF-α, interleukin (IL)-1a, IL-1, IL-2, IL-6, and other cytokines were found in higher concentrations in patients with T1DM. Even more importantly, oxidative stress contributes significantly to the severity and course of COVID- 19's significant role in the progression and severity of COVID-19 diseases. Severe glucose excursions, a defining characteristic of type 1 diabetes, are widely recognized for their potent role as mediating agents of oxidative stress via several routes, such as heightened production of advanced glycation end products (AGEs) and activation of protein kinase C (PKC). Furthermore, persistent endothelial dysfunction and hypercoagulation found in T1DM may impair microcirculation and endothelium, which could result in the development of various organ failure and acute breathing syndrome.

Type 1 diabetes mellitus (T1D) is a complicated illness marked by the death of insulin- producing pancreatic beta cells, which ultimately leads to insulin insufficiency and hyperglycemia. T lymphocytes are considered to destroy pancreatic beta cells in the etiology of T1D as a result of hereditary and environmental factors. Although the latter factors are very important causes of T1D development, this disease is very genetically predisposed, so there is a significant genetic component to T1D susceptibility. Among the T1D-associated gene mutations, those that affect genes that encode the traditional Human Leukocyte Antigens (HLA) entail the highest risk of T1D development. Accordingly, the results of decades of genetic linkage and association studies clearly demonstrate that mutations in the HLA genes are the most associated mutations with T1D. They can, therefore, be used as biomarkers for prediction strategies and may even prove to be of value for personalized treatments. Other immunity-associated genetic loci are also associated with higher T1D risk. Indeed, T1D is considered an autoimmune disease. Its prevalence is rising globally, especially among children and young people. Given the global rise of, and thus interest in, autoimmune diseases, here we present a short overview of the link between immunity, especially HLA, genes and T1D.

Background: Diabetes and hypertension are major global health challenges aggravated by COVID-19's impact on healthcare and lifestyle factors. This study aims to compare the prevalence and associated socio-demographic factors of these conditions before and after the pandemic (2019 vs. 2022). Materials and Methods: We used data from Italy's "Aspects of Daily Life" survey; 74,294 adults were included. Results: Results show a rise in diabetes prevalence from 7.76% in 2019 to 8.49% in 2022 (p < 0.05), while hypertension did not show this. Logistic regression analysis for the years 2019 and 2022 revealed a statistically significant association between the year 2022 and increased odds of diabetes (OR = 1.08, p = 0.008). BMI's role as a risk factor intensified, with higher odds ratios (ORs) for both conditions in overweight and obese individuals in 2022. For example, obesity-related ORs for diabetes increased from 2.45 (95%CI 1.73-3.47) in 2019 to 3.02 (95%CI 2.09-4.35) in 2022, and for hypertension from 2.86 (95%CI 2.28-3.58) to 3.64 (95%CI 2.87-4.61). Lower education levels also showed a greater association with hypertension risk in 2022; subjects with only middle or high school diplomas had significantly higher ORs than individuals with higher education; there was a non-significant trend in 2019. However, diabetes risk associated with lower education remained stable and significant in both years. Conclusions: These findings suggest that the pandemic may have increased risk factors for diabetes and hypertension, particularly BMI and educational level, compared with the literature on the increased burden of chronic diseases during COVID-19.

This review aims to present current data on the course of COVID-19 in patients with Cushing syndrome (CS) and discuss treatment for CS during to the pandemic.

Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Cushing syndrome", "Hypercortisolism" and "Glucocorticoid".

Chronic hypercortisolism has been reported to increase infectious risk and worsens prognostic of patients with COVID-19 potentially due to its direct impact on the immune system: lymphopenia, impairment of monocytes and neutrophils activity, diminution of complement activation. Main metabolic complications of CS - i.e. diabetes, hypertension and obesity - have been recognized as COVID-19 complications risk factors. Patients with CS treated with steroidogenesis inhibitors might experience adrenal insufficiency during COVID-19. Special attention should be paid to patients with CS and COVID-19. The pandemic has impacted - and delayed - care of chronic illnesses including CS. Specific recommendations had been provided during the pandemic: favor telemedicine consultations, limit in-hospital explorations and postpone surgery when feasible.

There are enough evidence for an increased prevalence and severity of COVID-19 to recommend a specific attention and caution in patients with CS.

The novel coronavirus strain SARS-CoV-2 triggered the COVID-19 pandemic with severe economic and social ramifications. As the pathophysiology of SARS-CoV-2 infection in the respiratory system becomes more understood, growing evidence suggests that the virus also impacts the homeostasis-regulating neuroendocrine system, potentially affecting other organ systems.

This review explores the interactions between SARS-CoV-2 and the neuroendocrine system, highlighting the effect of this virus on various endocrine glands, including the brain, hypothalamus, pituitary, pineal, thyroid, parathyroid, adrenal glands, pancreatic islets, gonads, and adipose tissue. The viral invasion disrupts normal hormonal pathways, leading to a range of endocrine disorders, immune dysregulation, and metabolic disturbances.

There is potential for SARS-CoV-2 to induce autoimmune responses, exacerbate existing endocrine conditions, and trigger new-onset disorders. Understanding these interactions is crucial for developing treatment strategies that address not only the respiratory symptoms of COVID-19 but also its endocrine complications. The review emphasizes the need for further research to elucidate the long-term effects of SARS-CoV-2 on endocrine health.

Objective  To study the etiological and anatomical factors in pathophysiology of invasive fungal rhinosinusitis affecting the skull base. Design  Retrospective clinical study over 5 years. Setting  Single-center tertiary referral hospital. Materials and Methods  All cases of invasive fungal rhinosinusitis with clinicoradiological and/or operative evidence of anterior and central skull base, orbit, and orbital apex involvement with or without intracranial disease were included in the study. Patients with a sinonasal-palatal disease without the involvement of the skull base or orbit were excluded from the study. In addition, we assessed the risk factors such as coronavirus disease 2019 (COVID-19) infection, diabetes mellitus (DM), and other immunocompromised conditions. Results  There were 79 patients, of which 65.8% had skull base rhino-oribitocerebral mucormycosis (ROCM), and 34.2% had Aspergillus infection. The mean duration from onset of the symptom to presentation of ROCM was 36.75 ± 20.97 days, while for the Aspergillus group was 21 weeks. The majority of patients (66%) with ROCM presented after 30 days of symptom onset. Among ROCM patients, 88.7% had a history of COVID-19 infection, and 96% had DM. In 40.8% of patients with Aspergillus infection, the tissue diagnosis was unavailable, and galactomannan assay and clinicoradiological assessment were used for diagnosis. The most common area of the skull base involved was the pterygopalatine fossa (88.5%), followed by the infratemporal fossa (73.1%). The most common neurovascular structure (75%) involved was the pterygopalatine ganglion and the infraorbital nerve. Conclusion  With the increasing incidence of invasive fungal infections worldwide, particularly after the COVID-19 pandemic, it is crucial to understand the evolving nature of this disease. ROCM, documented in the literature to cause fulminant disease, became a chronic illness, possibly due to the improvement of the patient's immunity during the disease course.

The aim of the study was to determine the association between coronavirus disease 2019 (COVID-19) infection and diabetes management indices in patients with type 2 diabetes mellitus.

A single-center, retrospective, observational study of patients with type 2 diabetes mellitus at Kenwakai Hospital (Nagano, Japan) was conducted. Data of 95 patients (mean age, 72 ± 12 years; men, 67.4%) who visited between March 1, 2019 and February 28, 2022 were obtained from the hospital's electronic information system. COVID-19 was diagnosed by a chemiluminescent enzyme immunoassay (CLEIA).

There was no association between COVID-19 infection and age, sex, hemodialysis treatment status, or the Charlson Comorbidity Index. After adjustment for possible confounding factors, the incidence of COVID-19 infection was significantly correlated with HbA1c ≥7.0% (odds ratio [OR], 5.51; 95% confidence interval [CI], 1.30-23.26).

The results suggest an association between high HbA1c levels and COVID-19 infection in patients with type 2 diabetes mellitus. Appropriate management of diabetes mellitus, focusing on HbA1c levels, may help prevent COVID-19 infection and severe disease after infection.

As the world population recovers from the COVID-19 infection, a series of acute sequelae emerge including new incident diabetes. However, the association between COVID-19 infection and new incident diabetes is not fully understood. We purpose to determine the risk of new incident diabetes after COVID-19 infection.

PubMed, Embase, and Cochrane Library were used as databases to search for cohort studies published from database inception to February 4, 2024. Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the hazard ratio (HR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted to explore the potential influencing factors.

A total of 20 cohort studies with over 60 million individuals were included. The pooling analysis illustrates the association between COVID-19 infection and an increased risk of new incident diabetes (HR = 1.46; 95% CI: 1.38-1.55). In subgroup analysis, the risk of type 1 diabetes was HR=1.44 (95% CI: 1.13-1.82), and type 2 diabetes was HR=1.47 (95% CI: 1.36-1.59). A slightly higher risk of diabetes was found in males (HR=1.37; 95% CI: 1.30-1.45) than in females (HR=1.29; 95% CI: 1.22-1.365). The risk of incident diabetes is associated with hospitalization: non-hospitalized patients have an HR of 1.16 (95% CI: 1.07-1.26), normal hospitalized patients have an HR of 2.15 (95% CI: 1.33-3.49), and patients receiving intensive care have the highest HR of 2.88 (95% CI: 1.73-4.79).

COVID-19 infection is associated with an elevated risk of new incident diabetes. Patients ever infected with COVID-19 should be recognized as a high-risk population with diabetes.

https://www.crd.york.ac.uk/prospero, identifier CRD42024522050.

Obesity and COVID-19 are at the top of nowadays health concerns with significant crosstalk between each other. The COVID-19 pandemic negatively affected healthy lifestyles and increased obesity prevalence. Thus, there was a surge in anti-obesity products (AOPs) intake. Herein, we evaluated how the pandemic has affected slimming products' efficacy and safety in patients seeking weight reduction at an urban, weight management centre in Alexandria, Egypt. In addition, the effect of AOPs on COVID-19 infection severity was also appraised to detect whether AOPs can alter COVID-19 host cell entry and infective mechanisms, and thus, affect infection severity.

Patients were invited to complete an anonymous survey. The survey assessed self-reported changes in weight, the use of AOPs during the COVID-19 pandemic, COVID-19 infection severity, AOPs efficacy, and incidence of side effects. Inclusion criteria were obese patients above 18 years old who got infected by COVID-19 while receiving a single-ingredient AOP.

A total of 462 participants completed our anonymous validated questionnaire. Most of the participants were females (450; 98.4%) with BMI ranging from 24.98-58.46. Eligible participants were only 234 and the top-administered products were orlistat, liraglutide, metformin, green tea, cinnamon, Garcinia cambogia, and Gymnema Sylvestre. In most cases, AOPs intake was beneficial for COVID-19 infection, and most patients experienced mild-to-moderate COVID-19 symptoms. On the other hand, SARS-CoV-2 significantly interferes with AOPs' mechanisms of action which positively or negatively influences their efficacy and side effects incidence due to predictable pharmacological link.

Concurrent AOPs intake with COVID-19 infection is a two-sided weapon; AOPs attenuate COVID-19 infection, while SARS-CoV-2 interferes with efficacy and side effects incidence of AOPs.

Our study aimed to describe the group of severe COVID-19 patients at an institutional level, and determine factors associated with different outcomes.

A retrospective chart review of patients admitted with severe acute hypoxic respiratory failure due to COVID-19 infection. Based on outcomes, we categorized 3 groups of severe COVID-19: (1) Favorable outcome: progressive care unit admission and discharge (2) Intermediate outcome: ICU care (3) Poor outcome: in-hospital mortality.

Eighty-nine patients met our inclusion criteria; 42.7% were female. The average age was 59.7 (standard deviation (SD):13.7). Most of the population were Caucasian (95.5%) and non-Hispanic (91.0%). Age, sex, race, and ethnicity were similar between outcome groups. Medicare and Medicaid patients accounted for 62.9%. The average BMI was 33.5 (SD:8.2). Moderate comorbidity was observed, with an average Charlson Comorbidity index (CCI) of 3.8 (SD:2.6). There were no differences in the average CCI between groups(p = 0.291). Many patients (67.4%) had hypertension, diabetes (42.7%) and chronic lung disease (32.6%). A statistical difference was found when chronic lung disease was evaluated; p = 0.002. The prevalence of chronic lung disease was 19.6%, 27.8%, and 40% in the favorable, intermediate, and poor outcome groups, respectively. Smoking history was associated with poor outcomes (p = 0.04). Only 7.9% were fully vaccinated. Almost half (46.1%) were intubated and mechanically ventilated. Patients spent an average of 12.1 days ventilated (SD:8.5), with an average of 6.0 days from admission to ventilation (SD:5.1). The intermediate group had a shorter average interval from admission to ventilator (77.2 hours, SD:67.6), than the poor group (212.8 hours, SD:126.8); (p = 0.001). The presence of bacterial pneumonia was greatest in the intermediate group (72.2%), compared to the favorable group (17.4%), and the poor group (56%); this was significant (p<0.0001). In-hospital mortality was seen in 28.1%.

Most patients were male, obese, had moderate-level comorbidity, a history of tobacco abuse, and government-funded insurance. Nearly 50% required mechanical ventilation, and about 28% died during hospitalization. Bacterial pneumonia was most prevalent in intubated groups. Patients who were intubated with a good outcome were intubated earlier during their hospital course, with an average difference of 135.6 hours. A history of cigarette smoking and chronic lung disease were associated with poor outcomes.

COVID-19 is still a major public health concern, mainly due to the persistence of symptoms or the appearance of new symptoms. To date, more than 200 symptoms of long COVID (LC) have been described. The present review describes and maps its relevant clinical characteristics, pathophysiology, epidemiology, and genetic and nongenetic risk factors. Given the currently available evidence on LC, we demonstrate that there are still gaps and controversies in the diagnosis, pathophysiology, epidemiology, and detection of prognostic and predictive factors, as well as the role of the viral strain and vaccination.

Diabetic-range hyperglycemia has been reported for the first time in many patients during their hospitalization with coronavirus disease 2019 (COVID-19). This study was undertaken to determine the proportion of such patients who actually have new-onset diabetes mellitus rather than transient hyperglycemia during acute illness.

This descriptive study included patients with diabetic-range hyperglycemia first detected at or during admission for COVID-19 but no prior history of diabetes. The study protocol involved patient identification, data recording from the case-notes, and telephonic follow-ups. Blood sugar levels done at least two weeks after discharge or the last dose of steroids, whichever was later, were recorded, and patients were categorized as diabetic, pre-diabetic, or non-diabetic accordingly.

Out of 86 patients, ten (11.6%) were found to have developed diabetes, and 13 (15.1%) had pre-diabetes on follow-up. About 63 (73.3%) patients had become normoglycemic. Eight (80%) out of the ten patients with new-onset diabetes were on treatment, with five (50%) achieving the target glycemic levels. The associations of new-onset diabetes with age, gender, comorbidities, intensive care stay, and steroid administration were not found to be statistically significant (p-values 0.809, 0.435, 0.324, 0.402, and 0.289, respectively).

While a majority of post-COVID patients with diabetic-range hyperglycemia returned to a normoglycemic state after the acute illness had settled down, one in ten developed new-onset diabetes, and an additional one in seven had impaired glucose tolerance. Thus, regular glucose screening is crucial for such patients and lifestyle modifications should be encouraged to reduce the risk of diabetes. Loss to follow-up and reliance on a single set of blood sugar readings for classification were some of the limitations of this study.

The coronavirus disease 2019 (COVID-19) pandemic has led to an association between COVID-19 and pediatric diabetes. Studies have indicated the increased likelihood of children with COVID-19 infection developing diabetes. Our objective was to assess not only the increase in pediatric diabetes at our hospital and identify possible risk factors, but also to correlate the psychosocial changes resulting from the pandemic with new-onset diabetes.

We analyzed data from 58 children aged 1 to 18 years admitted to our hospital with new-onset diabetes between March 2020 and December 2021. The data included inflammatory biomarkers and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies (Abs), as well as the results of a lifestyle questionnaire.

The average number of hospital admissions per month for new-onset diabetes increased from 10 to 18 with the start of the pandemic. Of the 58 children in our analysis, 33% had positive SARS-CoV-2 IgG Ab, 31% had type 1 diabetes mellitus, and 62% had type 2 diabetes mellitus (T2DM). More than half (54%) were experiencing diabetic ketoacidosis. Those with T2DM were older, majority African American, had higher median body mass index (BMI) percentiles, and lower vitamin D levels. There were no significant correlations between any psychosocial risk factors and either diabetes type or SARS-CoV2 Ab status.

Despite the increased incidence of new-onset diabetes among children in Mississippi during the pandemic, this study was unable to demonstrate a significant correlation between COVID-19 infection and new-onset diabetes. The findings of this study highlighted the correlation between increased BMI and type 2 diabetes, underscoring the significant problems of obesity and diabetes in our study region. Further research is warranted.

Diabetes mellitus (DM) is a common comorbidity in COVID-19 subjects. Hyperglycemia at hospital admission identified as a major risk factor and is responsible for poor prognosis. Hematological and inflammatory parameters have been recognized as predictive markers of severity in COVID-19. In this clinical study, we aimed to assess the impact of hyperglycemia at hospital admission on hematological and several inflammatory parameters in COVID-19 patients. A total of 550 COVID-19 subjects were primarily categorized into two major groups (normoglycemic and hyperglycemic) based on random blood sugar levels. On the first day of hospitalization, subjects' oxygen saturation, random blood sugar, hematological variables, and inflammatory parameters were recorded. The hyperglycemic group exhibited higher levels of serum ferritin, total leukocyte count (TLC), lactate dehydrogenase (LDH), neutrophil count, and neutrophil-to-lymphocyte ratio (NLR). In contrast, oxygen saturation and lymphocyte count were lower compared to the normoglycemic group. Significantly elevated levels of hematological variables (TLC, neutrophil count, NLR) and inflammatory parameters (serum ferritin) were observed in the hyperglycemic group. Among inflammatory parameters, only serum ferritin levels showed statistical significance. This study supports the clinical association between hyperglycemia and an increased severity of COVID-19. Consequently, the identification of these parameters is a crucial and valuable prognostic indicator for assessing disease severity in hyperglycemic subjects.

Past literature on the development of type 1 diabetes (T1D) and type 2 diabetes (T2D) has emphasized the influence of exogenous factors, including viral infections, in the development of these conditions. The coronavirus disease 2019 (COVID-19) pandemic again highlighted the complicated connection between viral infection and the development of diabetes. The complex interplay of proinflammatory, genetic, and socioeconomic factors can help explain the increased incidence of T1D and T2D during the pandemic. Proposed pathophysiological mechanisms connecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to T1D include the expression of angiotensin enzyme 2 receptors on pancreatic islet cells, resultant proinflammatory states, and potential transient damage caused by viral entry. The intricate web of genetic factors, social determinants of health (including the rise of obesity), and the impact of proinflammatory states during SARS-CoV-2 infection on insulin resistance suggests mechanisms linking SARS-CoV-2 infection to the development of diabetes. [Pediatr Ann. 2024;53(7):e258-e263.].

Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing β-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic β-cells to meet the demand for insulin due to a relative β-cell deficit in the setting of peripheral insulin resistance. Both types of DM involve derangement of glucose metabolism and are metabolic diseases generally considered to be initiated by a combination of genetic and environmental factors. Viruses have been reported to play a role as infectious etiological factors in the initiation of both types of DM in predisposed individuals. Among the reported viral infections causing DM in humans, the most studied include coxsackie B virus, cytomegalovirus and hepatitis C virus. The recent COVID-19 pandemic has highlighted the diabetogenic potential of SARS-CoV-2, rekindling interest in the field of virus-induced diabetes (VID). This review discusses the reported mechanisms of viral-induced DM, addressing emerging concepts in VID, as well as highlighting areas where knowledge is lacking, and further investigation is warranted.

Mucormycosis is an opportunistic fungal disease that affects immunocompromised patients. With the advent of SARS-CoV-2, this opportunistic disease has increased.

A case series of 47 patients with COVID-19 associated mucormycosis have been analyzed. Demographic information, signs, symptoms, laboratory investigations, imaging studies, and their association with ICU admission and 30-day mortality were assessed.

Total number of 47 consecutive rhino-orbital cerebral mucormycosis (ROCM) cases were analyzed. Periorbital swelling was the most common sign among patients. Majority of cases had diabetes. All patients received liposomal Amphotericin B. Debridement was performed for all cases.

SARS-CoV-2 increases the susceptibility to mucormycosis infection in various ways. Uncontrolled level of HbA1c in all patients, even non-diabetic individuals, indicates hyperglycemia over the past three months. Diabetes, orbital exenteration, ptosis, periorbital swelling, DKA, LOC, brain involvement, and mechanical ventilation all correlated with a higher rate of ICU admission and 30-day mortality. In addition, a higher white blood cell count is related to the higher probability of ICU admission. While considering all of the inflammatory laboratory data and HbA1c could help predict 30-day mortality.

Emerging publications indicate that diabetes predisposes patients with COVID-19 to more severe complications, which is partly attributed to inflammatory condition. In the current review, we reviewed recent published literature to provide evidence on the role of insulin resistance (IR) in diabetes, the association between diabetes and COVID-19 severity and mortality, the impact of COVID-19 infection on incident new-onset diabetes, mechanisms responsible for IR in COVID-19 patients, and the predictive value of different surrogates of IR in COVID-19.

The literature search performs to find out studies that have assessed the association between IR surrogates and morbidity and mortality in patients with COVID-19.

We showed that there is a bulk of evidence in support of the fact that diabetes is a potent risk factor for enhanced morbidity and mortality in COVID-19 patients. COVID-19 patients with diabetes are more prone to remarkable dysglycemia compared to those without diabetes, which is associated with an unfavourable prognosis. Furthermore, SARS-COV2 can make patients predispose to IR and diabetes via activating ISR, affecting RAAS signaling pathway, provoking inflammation, and changing the expression of PPARɣ and SREBP-1. Additionally, higher IR is associated with increased morbidity and mortality in COVID-19 patients and different surrogates of IR can be utilized as a prognostic biomarker for COVID-19 patients.

Different surrogates of IR can be utilized as predictors of COVID-19 complications and death.

The pathogenesis of diabetes and its microvascular complications are intimately associated with renin angiotensin system dysregulation. Evidence suggests the angiotensin converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis regulates metabolic imbalances, inflammatory responses, reduces oxidative stress, and sustains microvascular integrity, thereby strengthening defences against diabetic conditions. This study aims to conduct a comprehensive analysis of the ACE2/Ang 1-7/MasR axis in diabetes and its microvascular complications over the past two decades, focusing on key contributors, research hotspots, and thematic trends.

This cross-sectional bibliometric analysis of 349 English-language publications was performed using HistCite, VOSviewer, CiteSpace, and Bibliometrix R for visualization and metric analysis. Primary analytical metrics included publication count and keyword trend dynamics.

The United States, contributing 105 articles, emerged as the most productive country, with the University of Florida leading institutions with 18 publications. Benter IF was the most prolific author with 14 publications, and Clinical Science was the leading journal with 13 articles. A total of 151 of the 527 author's keywords with two or more occurrences clustered into four major clusters: diabetic microvascular pathogenesis, metabolic systems, type 2 diabetes, and coronavirus infections. Keywords such as "SARS", "ACE2", "coronavirus", "receptor" and "infection" displayed the strongest citation bursts. The thematic evolution in this field expanded from focusing on the renin angiotensin system (2002-2009) to incorporating ACE2 and diabetes metabolism (2010-2016). The latter period (2017-2023) witnessed a significant surge in diabetes research, reflecting the impact of COVID-19 and associated conditions such as diabetic retinopathy and cardiomyopathy.

This scientometric study offers a detailed analysis of the ACE2/Ang 1-7/MasR axis in diabetes and its microvascular complications, providing valuable insights for future research directions.

In the general population, maternal COVID-19 is associated with worse maternal and fetal outcomes. Two previous studies have assessed COVID-19 clinical outcomes in pregnant women with multiple sclerosis (MS), but there are no data about maternal and fetal outcomes.

In this multicenter study, we aimed to assess maternal and fetal outcomes in pregnant women with MS and COVID-19 infection.

We recruited pregnant patients with MS who contracted COVID-19 and were followed up in Italian and Turkish Centers, during 2020-2022. A control group was extracted from a previous Italian cohort. Associations between group (COVID-19 or healthy patients) and clinical outcomes (maternal complications, fetal malformations, and spontaneous abortion) were investigated with a weighted logistic regression where propensity score-based inverse probability of treatment weighting (IPTW) approach was applied for adjusting for difference in baseline confounders.

In the multivariable analysis, COVID-19 during pregnancy was associated with a higher risk of maternal complications (odd ratio (OR) = 2.12; 95% confidence interval (CI) = 1.32-3.48; p = 0.002), while it was not associated with higher risk of spontaneous abortion and fetal malformations.

Our data indicate that COVID-19 during pregnancy increases the risk of maternal complications, while it seems to have no significant impact on fetal outcomes.

The COVID-19 pandemic with the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been one of the largest topics of discussion in the medical world over the last few years. Most of the research has focused on the risks and correlation of chronic diseases and immunosuppression with the severity and mortality of the viral infection. Less research has occurred in the setting of post-infectious sequelae and the long-term effects of COVID-19 with the development of chronic conditions and diseases, such as new-onset type 1 diabetes mellitus. The incidence of diabetic ketoacidosis (DKA) has increased during the COVID-19 pandemic, but the relationship between the two conditions remains to be fully understood. We report the case of a 24-year-old male who presents with malaise, polyuria, polydipsia, headache, and fatigue and was eventually found to be in diabetic ketoacidosis (DKA). He had a history of COVID-19 infection 12 weeks prior to this presentation. He also had a family history of DKA and type 1 diabetes mellitus. This case highlights the need to perform an in-depth workup for each patient with DKA and new-onset diabetes mellitus in order to find a potential cause of the autoimmune condition.

To find clinical and immunological signatures of the SARS-CoV-2 and the COVID-19 pandemic on children newly diagnosed with type 1 diabetes (T1D).

A single-centre, retrospective, observational study comparing the clinical and immunological characteristics of children diagnosed with T1D the year before and during the first 2 years of the COVID-19 pandemic. Data extracted from the medical records included clinical and demographic parameters, COVID-19 PCR results and the presence of anti-islet, thyroid and celiac-related antibodies. Also obtained from the medical records was a family history of T1D, celiac disease and autoimmune thyroid disease in a first-degree family member.

A total of 376 children were diagnosed with T1D during the study period. A total of 132 in the pre-COVID era and 246 in the first 2 years of the pandemic. At diagnosis, the pH in children with DKA was lower, and HbA1c tended to be higher in the COVID-19 group compared to the pre-COVID-19 group (7.30 [7.18, 7.35] vs 7.33 [7.19, 7.36], p = 0.046) and (110.9 [86.9, 129.5] vs 100 [80.3, 129.5], p = 0.067]) respectively. Multiple islet antibodies (IA) were significantly more common among patients in the pre-COVID-19 group compared to the COVID-19 group (72% vs 61%, p = 0.032). Tissue transglutaminase antibodies were more common among children diagnosed in the COVID-19 compared to the pre-COVID group (16.6% vs 7.9%, p = 0.022).

Our findings suggest that SARS-CoV-2 and the environmental alterations caused by the pandemic affected the clinical characteristics and the immunological profile of children diagnosed with T1D. It is, therefore, plausible that the virus plays a role in the autoimmune process causing T1D.

Our aim was to highlight the clinical characteristics and determine the risk factors associated with severe and non-severe COVID-19 infection.

A retrospective review was conducted on clinical data obtained from patients with COVID-19 infection, admitted to the emergency department between November 2022 and January 2023. Total of 1684 participants were categorized into severe (312 cases,18.53%) and non-severe (1,372 cases,81.47%) cohorts. Logistic regression was utilized for multivariate analysis, with a P-value less than 0.05 signifying a significant difference between the groups.

The study consisted of 952 males (56.53%) and 732 females (43.47%) participants. The age distribution ranged from 18 to 93 years in both cohorts. There were statistically significant differences between the clinical symptoms of the severe and non-severe cohorts (P < 0.05). According to the multivariate statistical analysis, patients with more pronounced clinical manifestations had significantly elevated values related to age(P < 0.05), diabetes(P < 0.01), hypertension(P < 0.01), C-reactive protein (CRP) (P < 0.05), and lactate dehydrogenase (LDH) (P < 0.01) as compared to those presenting with milder symptoms.

The primary clinical presentations in both the cohorts were mostly similar. Predominant factors contributing to the severity of COVID-19 infection were age, diabetes, hypertension, elevated CRP levels, and increased LDH.

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

Despite evidence demonstrating the risks of developing diabetes mellitus because of SARS-CoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to the systemic inflammatory response. Since COVID-19 is known to induce these conditions, further investigation is necessary to fully understand its long-term effects on human health. Consequently, it is essential to consider the effect of the COVID-19 pandemic when predicting the prevalence of diabetes mellitus in the future, especially since the incidence of diabetes mellitus was already on the rise before the pandemic. Additional research is required to fully comprehend the impact of SARS-CoV-2 infection on glucose tolerance and insulin sensitivity. Therefore, this article delves deeper into the current literature and links the perceived relationship between SARS-CoV-2 and diabetes. In addition, the article highlights the necessity for further research to fully grasp the mechanisms that SARS-CoV-2 utilises to induce new-onset diabetes. Where understanding and consensus are reached, therapeutic interventions to prevent the onset of diabetes could be proposed. Lastly, we propose advocating for the regular screening of diabetes and pre-diabetes, particularly for the high-risk population with a history of COVID-19 infection.

A sudden surge of Mucormycosis cases during the second wave of Covid 19 was observed in certain parts of India. The reasons for this upsurge remain unknown. However its impact on the overall healthcare system was quite overwhelming. In this context this study was decided to estimate and assess the spectrum of orbital involvement in patients with Mucormycosis, to find its association with coexisting disease entities if any, and at the same time evaluate the therapeutic response to established treatment regimens.

This descriptive longitudinal study was conducted over a period of six months. Patients presenting with symptoms of Mucormycosis were jointly evaluated by a multi speciality team. After confirmation of diagnosis, patients were treated with intravenous Amphotericin B, surgical debridement of affected sinuses and orbital exenteration when indicated. They were followed up for three months after discharge.

Forty-three patients were enrolled in this study. Thirty-seven (86.04%) were COVID positive. All of them had history of steroid exposure during COVID treatment. Ninety five percent of study participants had diabetes mellitus. Twenty-seven (62.79%) patients had orbital involvement. Most common clinical presentation was peri-orbital or facial pain and edema. Besides medical treatment, thirty-nine patients (90.69%) required sinus debridement and nine patients (20.9%) required orbital exenteration. Thirteen patients (30.23%) expired during the follow up period. With treatment disease regressed in twenty patients (46.51%).

Diabetes and use of steroids to prevent anticipated cytokine storm may be the inciting factors for Orbital Mucormycosis in COVID patients. Early diagnosis, treatment and control of risk factors are keys for recovery and survival..

Coronavirus disease 2019 (COVID-19)-induced new-onset diabetes has raised widespread concerns. Increased glucose concentration and insulin resistance levels were observed in the COVID-19 patients. COVID-19 patients with newly diagnosed diabetes may have worse clinical outcomes and can have serious consequences. The types and exact mechanisms of COVID-19-caused diabetes are not well understood. Understanding the direct effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic beta cells and insulin target metabolism organs, such as the liver, muscle, and adipose tissues, will provide new ideas for preventing and treating the new-onset diabetes induced by COVID-19.

Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women, especially those with gestational diabetes mellitus (GDM), has yet to be fully understood. This review aims to examine the interaction between GDM and COVID-19 and to elucidate the pathophysiological mechanisms underlying the comorbidity of these two conditions.

We performed a systematic literature search using the databases of PubMed, Embase, and Web of Science with appropriate keywords and MeSH terms. Our analysis included studies published up to January 26, 2023.

Despite distinct clinical manifestations, GDM and COVID-19 share common pathophysiological characteristics, which involve complex interactions across multiple organs and systems. On the one hand, infection with severe acute respiratory syndrome coronavirus 2 may target the pancreas and placenta, resulting in β-cell dysfunction and insulin resistance in pregnant women. On the other hand, the hormonal and inflammatory changes that occur during pregnancy could also increase the risk of severe COVID-19 in mothers with GDM. Personalized management and close monitoring are crucial for treating pregnant women with both GDM and COVID-19.

A comprehensive understanding of the interactive mechanisms of GDM and COVID-19 would facilitate the initiation of more targeted preventive and therapeutic strategies. There is an urgent need to develop novel biomarkers and functional indicators for early identification and intervention of these conditions.

To investigate hormonal status in patients with long-COVID and explore the interrelationship between hormone levels and long-COVID symptoms.

Prospective observational study.

Patients who visited our long-COVID outpatients' clinic due to long-COVID symptoms from February 2021 to December 2022.

Total triiodothyronine, free thyroxine, thyrotropin, thyroglobulin, anti-thyroperoxidase, and antithyroglobulin autoantibodies were measured for thyroid assessment. Other hormones measured were growth hormone, insulin-like growth factor 1 (IGF-1), adrenocorticotropic hormone (ACTH), serum cortisol, dehydroepiandrosterone sulfate (DHEA-S), total testosterone, plasma insulin, and C-peptide. Blood glucose and glycosylated hemoglobin were also measured. To assess adrenal reserve, an ACTH stimulation test was performed. The fatigue assessment scale (FAS) was used to evaluate fatigue severity.

Eighty-four adult patients were included. Overall, 40.5% of the patients had at least one endocrine disorder. These included prediabetes (21.4%), low DHEA-S (21.4%), subclinical hypothyroidism (3.6%), non-specific thyroid function abnormality (7.1%), thyroid autoimmunity (7.1%), low testosterone in males (6.6%), and low IGF-1 (3.6%). All patients had normal adrenal reserve. Long-COVID-19 symptoms were present in all patients and the most commonly reported symptom was fatigue (89.3%). The FAS score was higher than normal (≥ 22) in 42.8% of patients. There were no associations between patients' symptoms and hormone levels. Diabetic patients reported confusion (p = 0.020) and hair loss (p = 0.040) more often than non-diabetics.

The evaluation of endocrine function 3 months after a positive SARS-CoV2 test revealed only subclinical syndromes. The vast majority of patients reported mainly fatigue, among other symptoms, which were unrelated, however, to endocrine function.

First described in December 2019 in Wuhan (China), COVID-19 disease rapidly spread worldwide, constituting the biggest pandemic in the last 100 years. Even if SARS-CoV-2, the agent responsible for COVID-19, is mainly associated with pulmonary injury, evidence is growing that this virus can affect many organs, including the heart and vascular endothelial cells, and cause haemostasis, CNS, and kidney and gastrointestinal tract abnormalities that can impact in the disease course and prognosis. In fact, COVID-19 may affect almost all the organs. Hence, SARS-CoV-2 is essentially a systemic infection that can present a large number of clinical manifestations, and it is variable in distribution and severity, which means it is potentially life-threatening. The goal of this comprehensive review paper in the series is to give an overview of non-pulmonary involvement in COVID-19, with a special focus on underlying pathophysiological mechanisms and clinical presentation.

Inflammation is a predictor of severe complications in patients with COVID-19 infection under a variety of clinical settings. A few studies suggested that COVID-19 infection was a trigger of hyperglycemic crises including diabetic ketoacidosis (DKA) and/or hyperglycemic hyperosmolar state (HHS). However, the association between inflammation and hyperglycemic crises in diabetic patients with COVID-19 infection is unclear.

One hundred and twenty-four patients with type 2 diabetes mellitus (T2DM) and COVID-19 infection from January 2023 to March 2023 were retrospectively analyzed. Demographic, clinical, and laboratory data, especially inflammatory markers including white blood cell (WBC), neutrophils, neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP) and procalcitonin (PCT) were collected and compared between patients with or without DKA and/or HHS. Multivariable logistic regression analysis was conducted to explore the association between inflammatory biomarkers and the prevalence of hyperglycemic crises. Patients were followed up 6 months for outcomes.

Among 124 diabetic patients with COVID-19, 9 were diagnosed with DKA or HHS. Comparing COVID-19 without acute diabetic complications (ADC), patients with DKA or HHS showed elevated levels of c-reactive protein (CRP, P=0.0312) and procalcitonin (PCT, P=0.0270). The power of CRP and PCT to discriminate DKA or HHS with the area under the receiver operating characteristics curve (AUROC) were 0.723 and 0.794, respectively. Multivariate logistic regression indicated 1.95-fold and 1.97-fold increased risk of DKA or HHS with 1-unit increment of CRP and PCT, respectively. However, neither CRP nor PCT could predict poor outcomes in diabetic patients with COVID-19.

In this small sample size study, we firstly found that elevated serum CRP and PCT levels increased the risk of hyperglycemic crises in T2DM patients with COVID-19 infection. More study is needed to confirm our findings.

We present a case of anion gap euglycemic diabetic ketoacidosis (EuDKA) in a patient with COVID-19 infection. Patients with diabetes mellitus are at increased risk of severe illness, and hyperglycaemia is associated with higher morbidity and mortality in patients infected with COVID-19.

A 76-year-old male with diabetes mellitus treated with SGLT2 inhibitor tested positive for COVID-19 infection on day 3 after his admission. In the emergency room he had a high anion gap metabolic acidosis and a blood glucose of 248 mg/dl. His urine tested strongly positive for ketones. A diagnosis of euglycemic diabetic ketoacidosis was made and he was treated with intravenous insulin and normal saline; his antidiabetic medications were stopped. His metabolic acidosis gradually resolved, and he was discharged.

Euglycemic diabetic ketoacidosis is a rare complication of COVID-19 infection. It is defined by the American Diabetes Association as the triad of anion gap metabolic acidosis with arterial pH <7.3, serum bicarbonate <18 mmol/l and ketonuria or ketonemia. It is a life-threatening complication which usually occurs in type 1 diabetes mellitus patients but may also occur in type 2 diabetes mellitus patients. As described earlier, it is associated with hyperglycaemia but if blood glucose is low or near normal but <250 mg/dl it is then named euglycemic diabetic ketoacidosis. Patients treated with SGLT2 inhibitors are at increased risk of euglycemic diabetic ketoacidosis.

COVID-19 infection precipitated euglycemic diabetic ketoacidosis in our patient. SGLT2 inhibitors must be stopped when this adverse reaction occurs. As their use increases, the risk of this adverse reaction is higher as well. Their prescription should be restricted to trained physicians who are able to educate their patients and treat them appropriately in situations that may arise.

COVID-19 infected patients are at increased risk of developing diabetic ketoacidosis or euglycemic ketoacidosis when treated with SGLT-2 inhibitors.It is practical to discontinue the drug at the onset of any symptoms consistent with acute infection to prevent the development of euglycemic diabetic ketoacidosis.