Implications of an HbA1c-based Diabetes Screening on Prevalence and Effect of Dysglycemia in Patients With COVID-19.

CONTEXT: In patients with severe acute respiratory syndrome coronavirus type 2 infection, diabetes is associated with poor COVID-19 prognosis. However, case detection strategy is divergent and reported prevalence varies from 5% to 35%. OBJECTIVE: We examined how far the choice of screening tools affects the detection rate of dysglycemia and in consequence the estimation of diagnosis-associated risk for moderate (mo) or severe (s) COVID-19. METHODS: Non-intensive care unit inpatients with COVID-19 were screened systematically at admission for diabetes (D) and prediabetes (PreD) by glycated hemoglobin A1c (HbA1c) (A), random blood glucose (B), and known history (C) from November 1, 2020 to March 8, 2021. Dysglycemia rate and effect on COVID-19 outcome were analyzed in 2 screening strategies (ABC vs BC). RESULTS: A total of 578 of 601 (96.2%) of admitted patients were screened and analyzed. In ABC, prevalence of D and PreD was 38.2% and 37.5%, respectively. D was significantly associated with an increased risk for more severe COVID-19 (adjusted odds ratio [aOR] [moCOVID-19]: 2.27, 95% CI, 1.16-4.46 and aOR [sCOVID-19]: 3.26, 95% CI, 1.56-6.38). Patients with PreD also presented more often with more severe COVID-19 than those with normoglycemia (aOR [moCOVID-19]: 1.76, 95% CI, 1.04-2.97 and aOR [sCOVID-19]: 2.41, 95% CI, 1.37-4.23). Screening with BC failed to identify only 96% of PreD (206/217) and 26.2% of D diagnosis (58/221) and missed associations of dysglycemia and COVID-19 severity. CONCLUSION: Pandemic conditions may hamper dysglycemia detection rate and in consequence the awareness of individual patient risk for COVID-19 severity. A systematic diabetes screening including HbA1c reduces underdiagnosis of previously unknown or new-onset dysglycemia, and enhances the quality of risk estimation and access of patients at risk to a diabetes-specific intervention.

The Fungal Gut Microbiome Exhibits Reduced Diversity and Increased Relative Abundance of Ascomycota in Severe COVID-19 Illness and Distinct Interconnected Communities in SARS-CoV-2 Positive Patients.

Clinical and experimental studies indicate that the bacterial and fungal gut microbiota modulates immune responses in distant organs including the lungs. Immune dysregulation is associated with severe SARS-CoV-2 infection, and several groups have observed gut bacterial dysbiosis in SARS-CoV-2 infected patients, while the fungal gut microbiota remains poorly defined in these patients. We analyzed the fungal gut microbiome from rectal swabs taken prior to anti-infective treatment in 30 SARS-CoV-2 positive (21 non-severe COVID-19 and 9 developing severe/critical COVID-19 patients) and 23 SARS-CoV-2 negative patients by ITS2-sequencing. Pronounced but distinct interconnected fungal communities distinguished SARS-CoV-2 positive and negative patients. Fungal gut microbiota in severe/critical COVID-19 illness was characterized by a reduced diversity, richness and evenness and by an increase of the relative abundance of the Ascomycota phylum compared with non-severe COVID-19 illness. A dominance of a single fungal species with a relative abundance of >75% was a frequent feature in severe/critical COVID-19. The dominating fungal species were highly variable between patients even within the groups. Several fungal taxa were depleted in patients with severe/critical COVID-19.The distinct compositional changes of the fungal gut microbiome in SARS-CoV-2 infection, especially in severe COVID-19 illness, illuminate the necessity of a broader approach to investigate whether the differences in the fungal gut microbiome are consequences of SARS-CoV-2 infection or a predisposing factor for critical illness.

[Systemic inflammation, "sickness behavior" and expectations : What role do expectations play in inflammation-associated symptoms?] / Systemische Entzündung, "Sickness Behavior" und Erwartungsprozesse : Welche Rolle spielen Erwartungen bei entzündungsassoziierten Symptomen?

BACKGROUND: Systemic inflammation is accompanied by unspecific physical and psychological symptoms of sickness, including pain and affective symptoms. These symptoms (commonly called "sickness behavior") are mediated by the central nervous effects of immune messengers such as pro-inflammatory cytokines. While adaptive during acute inflammation, sickness symptoms can have detrimental effects on quality of life during chronic inflammation and may contribute to comorbidity in chronic pain conditions. Despite the high clinical relevance of sickness behavior, psychological interventions aiming to modulate sickness symptoms have hardly been investigated. One approach could be the use of expectation effects, since positive and negative expectations (placebo or nocebo effects) have been shown to have an influence on pain and affect-related symptoms. OBJECTIVES: Herein, we summarize immunological and psychobiological factors that contribute to pain in the context of sickness behavior, with a major focus on findings from experimental endotoxemia. Against this background, we discuss how expectations could help to improve immune-mediated sickness symptoms and outline potential psychological and psychobiological mechanisms underlying this putative effect.

A Pro-Inflammatory Gut Microbiome Characterizes SARS-CoV-2 Infected Patients and a Reduction in the Connectivity of an Anti-Inflammatory Bacterial Network Associates With Severe COVID-19.

The gut microbiota contributes to maintaining human health and regulating immune responses. Severe COVID-19 illness is associated with a dysregulated pro-inflammatory immune response. The effect of SARS-CoV-2 on altering the gut microbiome and the relevance of the gut microbiome on COVID-19 severity needs to be clarified. In this prospective study, we analyzed the gut microbiome of 212 patients of a tertiary care hospital (117 patients infected with SARS-CoV-2 and 95 SARS-CoV-2 negative patients) using 16S rRNA gene sequencing of the V3-V4 region. Inflammatory markers and immune cells were quantified from blood. The gut microbiome in SARS-CoV-2 infected patients was characterized by a lower bacterial richness and distinct differences in the gut microbiome composition, including an enrichment of the phyla Proteobacteria and Bacteroidetes and a decrease of Actinobacteria compared to SARS-CoV-2 negative patients. The relative abundance of several genera including Bifidobacterium, Streptococcus and Collinsella was lower in SARS-CoV-2 positive patients while the abundance of Bacteroides and Enterobacteriaceae was increased. Higher pro-inflammatory blood markers and a lower CD8+ T cell number characterized patients with severe COVID-19 illness. The gut microbiome of patients with severe/critical COVID-19 exhibited a lower abundance of butyrate-producing genera Faecalibacterium and Roseburia and a reduction in the connectivity of a distinct network of anti-inflammatory genera that was observed in patients with mild COVID-19 illness and in SARS-CoV-2 negative patients. Dysbiosis of the gut microbiome associated with a pro-inflammatory signature may contribute to the hyperinflammatory immune response characterizing severe COVID-19 illness.

Structural correlates of motor adaptation deficits in patients with acute focal lesions of the cerebellum.

Studies of cerebellar patients employing modern lesion-symptom mapping techniques have provided valuable insights into the contribution of the cerebellum to motor adaptation. In patients with chronic focal lesions of the cerebellum, the process of adapting reaching movements to force field (FF) and visuomotor rotation (VM) perturbations relies on different anatomical structures located primarily within the territory of the superior hand area. By contrast, results within the territory of the inferior hand area are less consistent. Compensatory mechanisms may have masked the contribution of the inferior hand area. To test this hypothesis, reaching adaptation to FF and VM perturbations was investigated in 24 patients with acute and subacute lesions of the cerebellum. High-resolution magnetic resonance images were acquired to perform voxel-based lesion-symptom mapping (VLSM). VLSM confirmed that distinct and only partially overlapping areas located primarily within the territory of the superior hand area were crucial for adaptation to FF and VM. More specifically, current results add to previous findings that lobule V is of particular importance in FF adaptation, whereas lobule VI plays a more important role in VM adaptation. No clear evidence for a contribution of the inferior hand area to either task was found. Reach adaptation appears to depend primarily on the superior hand area within the cerebellum.