Incidence, Risk Factors, and Outcomes of COVID-19 Infection in a Large Cohort of Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr. METHODS: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr. Comparisons in COVID-19 mortality, hospitalization, and incidence were made between SOTr and non-SOTr, and between different SOTr organs. Multivariate analysis was performed to identify risk factors for COVID-19 mortality and hospitalization. RESULTS: There were 600 SOTr (kidney, liver, heart, and lung) with COVID-19. Per person-year incidence of COVID-19 among SOTr was 10.0% versus 7.6% among non-SOTr (P < 0.0001). Compared with uninfected SOTr, infected SOTr were older (57.1 ± 14.0 versus 45.7 ± 17.9 y, P < 0.001), predominantly Hispanic/Latino (58.8% versus 38.6%, P < 0.0001), hypertensive (77.0% versus 23.8%; P < 0.0001), and diabetic (49.6% versus 13.0%; P = 0.0009). Compared with non-SOTr, infected SOTr had higher hospitalization (39.5% versus 6.0%; P < 0.0001), intensive care unit admission (29.1% versus 15.5%; P < 0.0001), and mortality (14.7% versus 1.8%; P < 0.0001) from COVID-19. Older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10), male gender (HR, 1.79; 95% CI, 1.11-2.86), and higher body mass index (HR, 1.04; 95% CI, 1.00-1.09; P = 0.047) were associated with increased mortality from COVID-19, whereas race, diabetes, and number/type of immunosuppressive medications were not. Among the different SOTr, COVID-19 mortality risk was lowest in liver recipients (HR, 0.34; 95% CI, 0.16-0.73) and highest in lung recipients (HR, 1.74; 95% CI, 0.68-4.42). CONCLUSIONS: SOTr have higher rates of hospitalization and mortality from COVID-19 compared with the general population. Among the SOTr, the incidence and outcomes were distinct among different transplantation types.

New-Onset Diabetes Mellitus, Hypertension, Dyslipidaemia as Sequelae of COVID-19 Infection-Systematic Review.

As the population recovers from the coronavirus disease 2019 (COVID-19) pandemic, a subset of individuals is emerging as post-coronavirus disease (post-COVID) patients who experience multifactorial long-term symptoms several weeks after the initial recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this systematic review is to present the latest scientific reports that evaluate changes in glucose levels, blood pressure readings and lipid profiles after recovery from COVID-19 to verify the hypothesis that new-onset diabetes mellitus, arterial hypertension and dyslipidaemia are a possible sequela of a COVID-19 infection. The open access databases PubMed and Google Scholar were searched. Articles investigating patients with residual clinical signs and biochemical alteration indicating diabetes, hypertension and dyslipidaemia at least a month after recovering from COVID-19 were included. It has been shown that a select number of patients were diagnosed with new-onset diabetes, arterial hypertension and dyslipidaemia after COVID-19 infection. Alterations in glucose levels, blood pressure and lipid profiles months after initial infection shows the importance of considering diabetes mellitus, arterial hypertension and dyslipidaemia as part of the multifactorial diagnostic criteria post-COVID to better provide evidence-based clinical care.

Incidence of COVID-19 and Identification of Possible Risk Factors Associated with COVID-19 in Acute Renal Transplant Recipients in Pakistan.

BACKGROUND Renal transplant recipients are susceptible to increased mortality with COVID-19 infection. There is insufficient data regarding risk factors for COVID-19 disease acquisition. We aimed to identify them here. MATERIAL AND METHODS We enrolled Pakistani renal transplant recipients from February 10, 2020, to March 18, 2021, and actively tracked their baseline health status, transplant characteristics, comorbidities, immunosuppressive therapies, and post-transplant follow-ups until September 2021. Furthermore, we formulated 2 questionnaires for their compliance assessment with COVID-19-preventive measures. We also identified COVID-19 disease acquisition, symptomatology, and management. RESULTS Among the 50 enrolled patients, 14 (28%) patients developed COVID-19, which is higher than the incidence observed in general Pakistani population (0.55%). Their mean age was 35.38 years ±11.69 SD years, and 82% of patients were males. The following factors were independently associated with COVID-19 disease: female gender (P value: 0.042), diabetes mellitus (P value: 0.002), anti-thymocyte globulin (ATG) induction (P value: 0.006), in-person follow-ups (P value: 0.000), prolonged immediate and late post-transplant hospital stays (P value: 0.019 and 0.000, respectively), raised post-transplant serum creatinine (P value: 0.019), and COVID-19 protective measures non-compliance (P value: 0.000). Out of 14 infected recipients, 92.85% required symptomatic management and overall mortality was 0%. CONCLUSIONS Female gender, diabetes mellitus, ATG induction, in-person follow-ups, prolonged hospital stays, raised post-transplant serum creatinine, and COVID-19-protective measures non-compliance were associated with the higher acquisition of SARS-CoV-2 infection. By taking concrete measures against these risk factors, we can continue renal transplants, as overall mortality was lower than in the general Pakistani population (2%).

COVID-19 in Kidney Transplant Recipients With Diabetes Mellitus: A Propensity Score Matching Analysis.

Kidney transplant recipients present higher rates of pre-existing comorbidities, in particular diabetes mellitus (DM), hypertension, and cardiac disease. We aimed to verify the main risk factors related to DM that contribute to COVID-19 progression and mortality in a kidney transplant setting. From March to August 2020, we evaluated 300 kidney transplant recipients affected by COVID-19. We used propensity score matching (PSM) to estimate the impact of DM on COVID-19. After matching, all baseline characteristics were well balanced between those with and without DM (n = 100 in each group). Case fatality rate, the requirement of invasive mechanical ventilation (IMV), and acute kidney injury (AKI) were associated with previous fasting blood glucose, and C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels on admission. These findings were similar in kidney transplant patients with and without DM. Glycemia on admission and estimated glomerular filtration rate (eGFR) either on admission or basal correlated to the need of IMV and development of AKI, respectively. Poor glycaemic control, eGFR, markers of inflammation (CRP) and tissue damage (LDH) were indicative of COVID-19 burden in kidney transplant recipients and may be useful tools for risk-stratifying this population, independently of the DM status, during the pandemic.

Associations of Habitual Mineral Intake with New-Onset Prediabetes/Diabetes after Acute Pancreatitis.

Associations between habitual dietary intake of minerals and glucose metabolism have been extensively studied in relation to metabolic disorders. However, similar research has yet to be conducted in individuals after acute pancreatitis (AP). The main aim was to investigate the associations between habitual intake of 13 minerals and glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Associations between the dietary intake of minerals and markers of glucose metabolism (glycated haemoglobin and fasting plasma glucose) were also studied. The EPIC-Norfolk food frequency questionnaire was used in a cross-sectional fashion to determine the habitual intake of 13 dietary minerals. ANCOVA as well as multiple linear regression analyses were conducted and five statistical models were built to adjust for covariates. The study included 106 individuals after AP. In the NODAP group, intake of 4 minerals was significantly less when compared with the NAP group: iron (B = -0.076, p = 0.013), nitrogen (B = -0.066, p = 0.003), phosphorous (B = -0.046, p = 0.006), and zinc (B = -0.078, p = 0.001). Glycated haemoglobin was significantly associated with iodine intake (B = 17.763, p = 0.032) and manganese intake (B = -17.147, p = 0.003) in the NODAP group. Fasting plasma glucose was significantly associated with manganese intake (B = -2.436, p = 0.027) in the NODAP group. Habitual intake of minerals differs between individuals with NODAP, T2DM, and NAP. Prospective longitudinal studies and randomised controlled trials are now warranted to further investigate the associations between mineral intake and NODAP.

Diabetes and COVID-19; A Bidirectional Interplay.

There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.

Rare and Unusual Follow-up Sequelae of Coronavirus Disease 2019: Splenic Mucormycosis in a Renal Transplant Recipient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with adverse outcomes in transplantation communities. Mucormycosis, although a rare infection, has been classically linked to organ transplantation and is associated with exceptionally high morbidity and mortality rates. In this pandemic era, the double infection of mucormycosis and COVID-19 is a lethal combination but is rarely described in the literature on organ transplantation. CASE PRESENTATION: This article presents the case of a young kidney transplant recipient with diabetes who acquired severe COVID-19, followed by disseminated mucormycosis. The patient was a health care worker who developed severe COVID-19, for which he received remdesivir, anticoagulation, and dexamethasone. No immunomodulatory therapy was used. His maximum oxygen support was bilevel positive airway pressure ventilation. His sugar levels were frequently deranged during the stay. He developed secondary sepsis with Klebsiella, followed by nonhealing lung consolidation. He later developed pleural effusion and splenic abscess, which was detected incidentally. He underwent an emergency splenectomy, the culture of which yielded mucormycosis. Liposomal amphotericin B 5 mg/kg was administered. The patient deteriorated, and a repeat laparotomy yielded gastric perforation, with pus culture showing mucormycosis. The patient died after a long hospital stay. CONCLUSIONS: The diagnosis and management of this dual infection during the pandemic is extremely challenging. In this case, the unusual location of mucormycosis complicating COVID-19 calls for a meticulous approach to opportunistic fungal infections in organ transplant recipients who are positive for COVID-19, especially in those patients with diabetes.

COVID-19-Induced New-Onset Diabetes: Trends and Technologies.

The coronavirus disease 2019 (COVID-19) global pandemic continues to spread worldwide with approximately 216 million confirmed cases and 4.49 million deaths to date. Intensive efforts are ongoing to combat this disease by suppressing viral transmission, understanding its pathogenesis, developing vaccination strategies, and identifying effective therapeutic targets. Individuals with preexisting diabetes also show higher incidence of COVID-19 illness and poorer prognosis upon infection. Likewise, an increased frequency of diabetes onset and diabetes complications has been reported in patients following COVID-19 diagnosis. COVID-19 may elevate the risk of hyperglycemia and other complications in patients with and without prior diabetes history. It is unclear whether the virus induces type 1 or type 2 diabetes or instead causes a novel atypical form of diabetes. Moreover, it remains unknown if recovering COVID-19 patients exhibit a higher risk of developing new-onset diabetes or its complications going forward. The aim of this review is to summarize what is currently known about the epidemiology and mechanisms of this bidirectional relationship between COVID-19 and diabetes. We highlight major challenges that hinder the study of COVID-19-induced new-onset of diabetes and propose a potential framework for overcoming these obstacles. We also review state-of-the-art wearables and microsampling technologies that can further study diabetes management and progression in new-onset diabetes cases. We conclude by outlining current research initiatives investigating the bidirectional relationship between COVID-19 and diabetes, some with emphasis on wearable technology.

SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes.

Evidence suggests an association between severe acute respiratory syndrome-cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immunolocalization in pancreatic cells of SARS-CoV-2-infected NHPs and patients who had died from coronavirus disease 2019 (COVID-19). We report expression of ACE2 in pancreatic islet, ductal, and endothelial cells in NHPs and humans. In pancreata from SARS-CoV-2-infected NHPs and COVID-19 patients, SARS-CoV-2 infected ductal, endothelial, and islet cells. These pancreata also exhibited generalized fibrosis associated with multiple vascular thrombi. Two out of 8 NHPs developed new-onset diabetes following SARS-CoV-2 infection. Two out of 5 COVID-19 patients exhibited new-onset diabetes at admission. These results suggest that SARS-CoV-2 infection of the pancreas may promote acute and especially chronic pancreatic dysfunction that could potentially lead to new-onset diabetes.

Ocular Surface Impairment After Coronavirus Disease 2019: A Cohort Study.

PURPOSE: This is a cohort study to evaluate the presence of objective signs and subjective symptoms of dry eye disease in postcoronavirus disease 2019 (COVID-19) patients compared with the control. METHODS: Prospective, observational, single-ctenter, cohort study. Sixty-four post-COVID-19 patients and 50 control were recruited. All participants underwent a complete ophthalmological examination including Ocular Surface Disease Index Questionnaire (OSDI), best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, Schirmer test type 1, tear break-up time test (tBUT), evaluation of conjunctival hyperemia, corneal staining, and tear film osmolarity test. RESULTS: The OSDI score was higher in the post-COVID-19 group in the quantitative and qualitative analysis (P < 0.001 and P =0.012, respectively). The mean tBUT in post-COVID-19 patients was 6.95 ± 4.07 seconds compared with a mean tBUT of 10.12 ± 3.90 seconds in the control group. The post-COVID-19 group showed a higher number of patients with a simultaneous impairment of the OSDI score and tBUT (P = 0.019). The Schirmer test results were strikingly significant both in the quantitative analysis and qualitative analysis (P <0.001 and P = 0.0014, respectively). Both quantitative analysis and qualitative analysis revealed a significant difference in tear osmolarity in the 2 groups. CONCLUSIONS: Comparing the ocular surface assessment of post-COVID-19 patients with heathy control, a statistically significant increase of dry eye disease has emerged both in subjective and objective evaluations. Our clinical results support the findings that suggested a susceptibility of the ocular surface to the virus, and it underlines the importance of the ocular surface assessment in post-COVID-19 patients for a correct diagnosis and therapy.

Pathophysiological Implication of Vitamin D in Diabetic Kidney Disease.

BACKGROUND: Vitamin D is a hormone regulating not only calcium and phosphate homeostasis but also, at the same time, exerting many other extraskeletal functions via genomic effects (gene transcription) and probably by non-genomic effects as well. Availability is ensured by dietary intake of its precursors and by de novo production via sunlight. Yet, vitamin D deficiency and insufficiency are very common across the globe and are connected to many pathophysiological states, for example, diabetes mellitus, allergies, autoimmune diseases, pregnancy complications, and recently have also been associated with worse COVID-19 clinical outcomes. SUMMARY: In this review, we summarize current knowledge about vitamin D metabolism in general, its role in diabetes mellitus (mainly type 2) and diabetic complications (mainly diabetic kidney disease), and potential therapeutic perspectives including vitamin D signalling as a druggable target. Key Messages: Vitamin D is not only a vitamin but also a hormone involved in many physiological processes. Its insufficiency or deficiency can lead to many pathological states.

The Independent Risk of Obesity and Diabetes and Their Interaction in COVID-19: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to assess whether diabetes mellitus (DM) or obesity is an independent risk factor for severe coronavirus disease 2019 (COVID-19) outcomes and to explore whether the risk conferred by one condition is modified by the other. METHODS: This retrospective cohort study of inpatient adults with COVID-19 used multivariable Cox regression to determine the independent effects of DM and obesity on the composite outcome of intubation, intensive care unit admission, or in-hospital mortality. Effect modification between DM and obesity was assessed with a statistical interaction term and an exploration of stratum-specific effects. RESULTS: Out of 3,533 patients, a total of 1,134 (32%) had DM, 1,256 (36%) had obesity, and 430 (12%) had both. DM and obesity were independently associated with the composite outcome (hazard ratio [HR] 1.14 [95% CI: 1.01-1.30] and HR 1.22 [95% CI: 1.05-1.43], respectively). A statistical trend for potential interaction between DM and obesity was observed (P = 0.20). Stratified analyses showed potential increased risk with obesity compared with normal weight among patients with DM (HR 1.34 [95% CI: 1.04-1.74]) and patients without DM (HR 1.18 [95% CI: 0.96-1.43]). CONCLUSIONS: DM and obesity are independent risk factors associated with COVID-19 severity. Stratified analyses suggest that obesity may confer greater risk to patients with DM compared with patients without DM, and this relationship requires further exploration.

Impact of COVID-19 Pandemic on the Outcomes in Patients With Critical Limb Threatening Ischaemia and Diabetic Foot Infection.

OBJECTIVE: Examine the impact of COVID-19 pandemic on the outcomes in patients with CLTI or DFI. BACKGROUND: Patients with CLTI and/or DFI are at risk of amputations if not treated in a timely manner. METHODS: We compared the outcomes in patients with CLTI or DFI during 2 periods; Period 1[P1] (15/03/2019-31/05/2019) and period 2[P2] (15/03/ 2020-31/05/2020- corresponding to COVID-19 pandemic). RESULTS: One hundred thirty-nine patients were treated in P1 [mean age 70 years (±11), Male:Female = 102:37] whereas 95 patients were treated in P2 [mean age 67 (±12), Male:Female = 64:31]. The 2 cohorts were matched regarding Rutherford category (P = 0.25) and GLASS classification (P = 0.38). Notably, the time from onset of symptom to clinical presentation was significantly longer [31 (1-105) days vs 27 (0-78) days, (P = 0.017)], whereas the time from presentation to first intervention was significantly shorter [3 (0-61) days vs 5 (0-65) days, (P = 0.013)] in P2 compared to P1. There was a significantly higher white cell count (P = 0.014) and CRP (P = 0.004) on admission in P2. Having treatment for CLTI or DFI in P2 was an independent predictor of worse primary patency rate and freedom from major adverse limb events. At 90 days, amputation-free survival and limb salvage were noticeably worse in P2 compared to P1 (amputation-free survival was 80% and 87% whereas limb salvage was 64% and 72% in P2 and P1, respectively). CONCLUSIONS: Patients with CLTI and DFI experienced a significantly delayed presentation with features of sepsis on admission in P2. Treatment in P2 was a predictor of worse primary patency and freedom from major adverse limb events and therefore close and long follow-up is advisable.

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.