Evidence suggests that immunogenicity to mRNA-based SARS-CoV-2 vaccination in immunosuppressed patients may be reduced. This study assessed the response to 2 doses of mRNA-based SARS-CoV-2 vaccine among 133 participants with underlying chronic inflammatory disease, many of whom were receiving glucocorticoids, B-cell depletion therapy, or other immunosuppressant therapy.

Hypo and Hyper have qualitatively different effects on cognitive function in T1DM that depend in part on the timing of exposure during development, independent of onset age. This information extends the known benefits of avoiding both Hypo and chronic Hyper during childhood to include preservation of specific cognitive skills.

Background: Individuals with Chronic Inflammatory Diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the potency of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. Methods: We conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+ binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. Results: Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization. Conclusions: CID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.

OBJECTIVE -Despite interest in the effects of type 1 diabetes on the developing brain, structural brain volumes in youth with this disease have not previously been examined. This study is the first to quantify regional brain volume differences in a large sample of youth with diabetes. RESEARCH DESIGN AND METHODS -Magnetic resonance images (MRIs)were acquired from youth with diabetes (n ϭ 108) and healthy sibling control subjects (n ϭ 51) aged 7-17 years. History of severe hypoglycemia was assessed by parent interview and included seizure, loss of consciousness, or requiring assistance to treat. A1C values since diagnosis were obtained from medical records; median A1C was weighted by duration of disease. Voxel-based morphometry was used to determine the relationships of prior hypo-and hyperglycemia to regional grey and white matter volumes across the whole brain.RESULTS -No significant differences were found between diabetic and healthy control groups in grey or white matter. However, within the diabetic group, a history of severe hypoglycemia was associated with smaller grey matter volume in the left superior temporal region. Greater exposure to hyperglycemia was associated with smaller grey matter volume in the right cuneus and precuneus, smaller white matter volume in a right posterior parietal region, and larger grey matter volume in a right prefrontal region.CONCLUSIONS -Qualitatively different relationships were found between hypo-and hyperglycemia and regional brain volumes in youth with type 1 diabetes. Future studies should investigate whether these differences relate to cognitive function and how these regions are affected by further exposure. Diabetes Care 30:2331-2337, 2007T ype 1 diabetes is known to have cumulative deleterious effects on the body, most notably on the retina, kidney, nerves, and blood vessels (1,2).The effects of diabetes on central nervous system structure and function are less well understood. A number of studies associate exposure to hypo-and hyperglycemia during childhood with deficits in specific cognitive domains (3,4). These findings suggest that during development, exposure to glycemic extremes may alter the structure or function of specific pathways or regions in the brain. Recent brain imaging studies in diabetic adults have reported differences in grey or white matter integrity associated with prior hypo-or hyperglycemia (5,6). However, the effects of diabetes on the developing brain have not been assessed in any largescale study to date (7). Assessing brain integrity earlier in the course of brain development and diabetes, followed by prospective monitoring, would be essential to determine when differences may emerge. Such knowledge could shed light on the neural basis of observed cognitive effects in children and adults with diabetes and determine whether there are developmental time periods during which the brain may be particularly vulnerable to the negative effects of hypoglycemia or hyperglycemia.The present study is the first to examine the structural integrity of t...

OBJECTIVE -Repeated severe hypoglycemia has been reported to reduce long-term spatial memory in children with type 1 diabetes. Early exposure to hypoglycemia may be more damaging to cognitive function than later exposure. Our goal was to determine whether the age at which severe hypoglycemia occurs modulates the impact of severe hypoglycemia frequency on long-term spatial memory.RESEARCH DESIGN AND METHODS -We combined data from three independent studies to obtain a sample of children aged 6 -18 years with type 1 diabetes (n ϭ 103) and nondiabetic control subjects (n ϭ 60). Each study evaluated previous severe hypoglycemia and tested short (5 s)-and long (60 s)-delay spatial memory with the spatial delayed response task. Type 1 diabetic participants were categorized as having zero, one to two, or three or more severe hypoglycemic episodes and as having their first severe hypoglycemic episode before or after 5 years of age. Information on chronic hyperglycemia (HbA 1c values) was also collected.RESULTS -We found that repeated severe hypoglycemia (more than three episodes) reduced long-delay spatial delayed response performance, particularly when severe hypoglycemic episodes began before the age of 5 years. Age of type 1 diabetes onset and estimates of chronic hyperglycemia did not influence performance.CONCLUSIONS -High frequency of and early exposure to severe hypoglycemia during development negatively affects spatial long-term memory performance. Diabetes Care 28:2372-2377, 2005S evere hypoglycemia is a significant and relatively common complication of insulin treatment in children with type 1 diabetes (1). The long-term cognitive effects of such episodes have been debated. One hypothesis is that severe hypoglycemia occurring early in development is more harmful to cognitive function than severe hypoglycemia later in development, but few data address this issue directly. If this hypothesis was correct, it could explain the consistent finding that early onset of type 1 diabetes predicts poorer cognitive function (2-5). Since only individuals with early onset of diabetes would be expected to experience early severe hypoglycemia, age of onset can be confounded with the age of first severe hypoglycemia. Although previous studies (6,7) have examined the impact of age of onset and of severe hypoglycemia history on cognitive function in children, none have established whether the age at which severe hypoglycemia occurs is important in determining cognitive outcome. It is possible that severe hypoglycemia frequency and timing are both important contributors to cognitive dysfunction in children with type 1 diabetes.We combined data from three studies, all of which found that severe hypoglycemia preferentially decreased spatial long-term memory in children with type 1 diabetes (8,9). We used these data to determine how the effects of severe hypoglycemia on spatial memory were modulated by the age at which severe hypoglycemia occurred. Further, we wanted to determine whether exposure to chronic hyperglycemia contributed t...