Risks of Severe COVID-19 Outcomes Among Patients With Diabetic Polyneuropathy in the United States.

CONTEXT: Diabetic neuropathy (DN) affects more than 50% of diabetic patients who are also likely to have compromised immune system and respiratory function, both of which can make them susceptible to the SARS-CoV-2 virus. OBJECTIVE: To assess the risk of severe COVID-19 illness among adults with DN, compared with those with no DN and those with no diabetes. SETTING: The analysis utilized electronic health records from 55 US health care organizations in the TriNetX research database. DESIGN: A retrospective cohort study. PARTICIPANTS: The analysis included 882 650 adults diagnosed with COVID-19 in January 2020 to June 2021, including 16 641 with DN, 81 329 with diabetes with no neuropathy, and 784 680 with no diabetes. OUTCOME MEASURES: The presence of health care utilization (admissions to emergency department, hospital, intensive care unit), 30-day mortality, clinical presentation (cough, fever, hypoxemia, dyspnea, or acute respiratory distress syndrome), and diagnostic test results after being infected affected by COVID-19. RESULTS: The DN cohort was 1.19 to 2.47 times more likely than the non-DN cohorts to utilize care resources, receive critical care, and have higher 30-day mortality rates. Patients with DN also showed increased risk (1.13-2.18 times) of severe symptoms, such as hypoxemia, dyspnea, and acute respiratory distress syndrome. CONCLUSIONS: Patients with DN had a significantly greater risk of developing severe COVID-19-related complications than those with no DN. It is critical for the public health community to continue preventive measures, such as social distancing, wearing masks, and vaccination, to reduce infection rates, particularly in higher risk groups, such as those with DN.

Duodenal Mucosal Expression of COVID-19-Related Genes in Health, Diabetic Gastroenteropathy, and Functional Dyspepsia.

CONTEXT: SARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19 are more likely to have severe disease is unknown. OBJECTIVE: We aimed to compare the duodenal mucosal expression of SARS-CoV-2 and inflammation-related genes in diabetes gastroenteropathy (DGE), functional dyspepsia (FD), and healthy controls. METHODS: Gastrointestinal transit, and duodenal mucosal mRNA expression of selected genes were compared in 21 controls, 39 DGE patients, and 37 FD patients from a tertiary referral center. Pathway analyses were performed. RESULTS: Patients had normal, delayed (5 FD [13%] and 13 DGE patients [33%]; P = 0.03 vs controls), or rapid (5 FD [12%] and 5 DGE [12%]) gastric emptying (GE). Compared with control participants, 100 SARS-CoV-2-related genes were increased in DGE (FDR < 0.05) vs 13 genes in FD; 71 of these 100 genes were differentially expressed in DGE vs FD but only 3 between DGE patients with normal vs delayed GE. Upregulated genes in DGE include the SARS-CoV2 viral entry genes CTSL (|Fold change [FC]|=1.16; FDR < 0.05) and CTSB (|FC|=1.24; FDR < 0.05) and selected genes involved in viral replication (eg, EIF2 pathways) and inflammation (CCR2, CXCL2, and LCN2, but not other inflammation-related pathways eg, IL-2 and IL-6 signaling). CONCLUSION: Several SARS-CoV-2-related genes were differentially expressed between DGE vs healthy controls and vs FD but not between DGE patients with normal vs delayed GE, suggesting that the differential expression is related to diabetes per se. The upregulation of CTSL and CTSB and replication genes may predispose to SARS-CoV2 infection of the gastrointestinal tract in diabetes.

What is the impact of microvascular complications of diabetes on severe COVID-19?

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.