Incidence, characteristics, risk factors and outcomes of diabetic ketoacidosis in COVID-19 patients: Comparison with influenza and pre-pandemic data.

AIMS: This study characterized incidence, patient profiles, risk factors and outcomes of in-hospital diabetic ketoacidosis (DKA) in patients with COVID-19 compared with influenza and pre-pandemic data. METHODS: This study consisted of 13 383 hospitalized patients with COVID-19 (March 2020-July 2022), 19 165 hospitalized patients with influenza (January 2018-July 2022) and 35 000 randomly sampled hospitalized pre-pandemic patients (January 2017-December 2019) in Montefiore Health System, Bronx, NY, USA. Primary outcomes were incidence of in-hospital DKA, in-hospital mortality, and insulin use at 3 and 6 months post-infection. Risk factors for developing DKA were identified. RESULTS: The overall incidence of DKA in patients with COVID-19 and influenza, and pre-pandemic were 2.1%, 1.4% and 0.5%, respectively (p < .05 pairwise). Patients with COVID-19 with DKA had worse acute outcomes (p < .05) and higher incidence of new insulin treatment 3 and 6 months post-infection compared with patients with influenza with DKA (p < .05). The incidence of DKA in patients with COVID-19 was highest among patients with type 1 diabetes (12.8%), followed by patients with insulin-dependent type 2 diabetes (T2D; 5.2%), non-insulin dependent T2D (2.3%) and, lastly, patients without T2D (1.3%). Patients with COVID-19 with DKA had worse disease severity and higher mortality [odds ratio = 6.178 (4.428-8.590), p < .0001] compared with those without DKA. Type 1 diabetes, steroid therapy for COVID-19, COVID-19 status, black race and male gender were associated with increased risk of DKA. CONCLUSIONS: The incidence of DKA was higher in COVID-19 cohort compared to the influenza and pre-pandemic cohort. Patients with COVID-19 with DKA had worse outcomes compared with those without. Many COVID-19 survivors who developed DKA during hospitalization became insulin dependent. Identification of risk factors for DKA and new insulin-dependency could enable careful monitoring and timely intervention.

Incidence of new-onset in-hospital and persistent diabetes in COVID-19 patients: comparison with influenza.

BACKGROUND: This study investigated the incidences and risk factors associated with new-onset persistent type-2 diabetes during COVID-19 hospitalization and at 3-months follow-up compared to influenza. METHODS: This retrospective study consisted of 8216 hospitalized, 2998 non-hospitalized COVID-19 patients, and 2988 hospitalized influenza patients without history of pre-diabetes or diabetes in the Montefiore Health System in Bronx, New York. The primary outcomes were incidences of new-onset in-hospital type-2 diabetes mellitus (I-DM) and persistent diabetes mellitus (P-DM) at 3 months (average) follow-up. Predictive models used 80%/20% of data for training/testing with five-fold cross-validation. FINDINGS: I-DM was diagnosed in 22.6% of patients with COVID-19 compared to only 3.3% of patients with influenza (95% CI of difference [0.18, 0.20]). COVID-19 patients with I-DM compared to those without I-DM were older, more likely male, more likely to be treated with steroids and had more comorbidities. P-DM was diagnosed in 16.7% of hospitalized COVID-19 patients versus 12% of hospitalized influenza patients (95% CI of difference [0.03,0.065]) but only 7.3% of non-hospitalized COVID-19 patients (95% CI of difference [0.078,0.11]). The rates of P-DM significantly decreased from 23.9% to 4.0% over the studied period. Logistic regression identified similar risk factors predictive of P-DM for COVID-19 and influenza. The adjusted odds ratio (0.90 [95% CI 0.64,1.28]) for developing P-DM was not significantly different between the two viruses. INTERPRETATION: The incidence of new-onset type-2 diabetes was higher in patients with COVID-19 than influenza. Increased risk of diabetes associated with COVID-19 is mediated through disease severity, which plays a dominant role in the development of this post-acute infection sequela. FUNDING: None.

COVID-19 and children.

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.

Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets.

Recent studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may induce metabolic distress, leading to hyperglycemia in patients affected by coronavirus disease 19 (COVID-19). We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. Although there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which could be abrogated by the use of anti-interleukin-1ß (IL-1ß), anti-IL-6, and anti-tumor necrosis factor α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19 revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2-specific viral RNA, along with the presence of several immature insulin granules or proinsulin, was detected in postmortem pancreatic tissues, suggestive of ß-cell-altered proinsulin processing, as well as ß-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islet function and survival by creating inflammatory conditions, possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19.

A Single Virtual Consult Reduces Severe Hyperglycemia in Patients Admitted with COVID19 Infection

Diabetes and hyperglycemia are risk factors for morbidity and mortality in hospitalized patients with COVID19. Subspecialty consultative resources to help front-line clinicians treat these conditions is often limited. We implemented a “Virtual Hyperglycemia Surveillance Service (VHSS)” to guide glucose management in COVID19 patients admitted to our 1541-bed academic medical center.

Natural mucosal barriers and COVID-19 in children.

BACKGROUNDCoronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease.METHODSClinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti-SARS-CoV-2 IgG and IgA were quantified in nasal fluid.RESULTSSARS-CoV-2 copies, angiotensin-converting enzyme 2, and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1ß protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died.CONCLUSIONThese findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.FUNDINGNIH grants R01 AI134367, UL1 TR002556, T32 AI007501, T32GM007288, P30 AI124414; an Albert Einstein College of Medicine Dean's COVID-19 Pilot Research Award; and the Eric J. Heyer, MD, PhD Translational Research Pilot Project Award.