Long-Term Comparison of 7 SARS-CoV-2 Antibody Assays in the North Zealand Covid-19 Cohort.

BACKGROUND: Throughout the coronavirus disease 2019 (Covid-19) pandemic numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays have been approved through Emergency Use Authorization and require further evaluation of sensitivity and specificity in clinical laboratory settings prior to implementation. METHODS: We included 1733 samples from 375 PCR-confirmed SARS-CoV-2-positive individuals of the North Zealand Covid-19 Cohort in an 8-month period. We investigated diagnostic sensitivity and specificity against consensus and PCR and interassay agreement over time for 5 SARS-CoV-2 immunoassays [Roche-nucleocapsid (NC)-total, Roche-receptor binding domain (RBD)-total, Siemens-RBD-IgG, Siemens-RBD-total, Thermo Fisher Scientific (TFS)-RBD-IgG] commercially available on automated platforms and 2 ELISA assays (TFS-RBD-total, Wantai-RBD-total). RESULTS: Early interassay discrepancy in up to 49% of samples decreased steadily during the first 18 days. By day 18, all assays had reached a plateau between 82.3% and 90.5% seropositivity compared to PCR. Assays ranked by closest agreement with the consensus model beyond day 18 (sensitivity/specificity against consensus) were as follows: Roche-RBD-total, 99.8%/100.0%; Wantai-RBD-total, 99.8%/99.7%; Roche-NC-total, 97.8%/100.0%; Siemens-RBD-total, 98.0%/98.7%; TFS-RBD-total, 96.9%/99.7%; TFS-RBD-IgG, 91.5%/100.0%; and Siemens-RBD-IgG, 94.6%/89.9%. We found that 7.8% of PCR-positive patients remained seronegative in all assays throughout the study. CONCLUSIONS: All included assays had sensitivities against consensus >90% past day 18. For the current recommended use of antibody assays to detect former, undocumented Covid-19, our data suggest the use of total antibody assays rather than IgG-specific assays due to higher long-term sensitivity. Finally, a nonresponding subpopulation of 7.8% in our cohort with persistent seronegative results raises concern of a possible substantial number of people with continued low protection following natural SARS-CoV-2 infection.

Fractionated free fatty acids and their relation to diabetes status after Roux-en-Y gastric bypass: A cohort study.

Bariatric surgery is associated with near-immediate remission of type 2 diabetes and recently suggested as a treatment for type 2 diabetes. Specifically, Roux-en-Y gastric bypass has been a focus of much research, but still, the mechanisms of action are only partly elucidated. We aim to investigate whether some mechanisms might be mediated by free fatty acids (FFAs). We measured eight fractionated FFAs before and up to 2 years after Roux-en-Y gastric bypass surgery in 207 patients, divided into three groups. One non-diabetic group, one diabetic group with post-operative remission and one diabetic group with persistent diabetes after surgery. Pre- and postoperative levels of fractionated FFAs were compared within and between groups. The sum of the measured FFAs were lower in the group with persistent diabetes, compared to the other groups. The pre-surgery level of linoleic acid in the group with persistent diabetes was significantly lower compared to the other two groups. The levels of fractionated FFAs decreased from pre-surgery to three months after surgery, except for oleic acid and arachidonic acid and for Docosahexaenoic acid (DHA) in the non-diabetic group. The FFAs with decreasing levels from pre-surgery to three months post-surgery are all precursors to oleic acid, arachidonic acid, and DHA, respectively, which may imply a drift, indicating that they need to be sustained at an acceptable level for optimal metabolic function. The fact that the sum of the measured FFAs is lower in the group with persistent diabetes may suggest that this group and the group with diabetes remission represent two distinct types of type 2 diabetes. It is proposed that linoleic acid could be used as a biomarker to determine the plausibility for type 2 diabetes remission after Roux-en-Y gastric bypass surgery.

Intestinal sensing and handling of dietary lipids in gastric bypass-operated patients and matched controls.

BACKGROUND: Altered meal-related gut hormone secretion seems important for weight loss and diabetes remission after Roux-en-Y gastric bypass (RYGB). Elucidating the responsible meal components and receptors could aid discovery of new treatments of obesity and diabetes. Enteroendocrine cells respond to digestion products of dietary triacylglycerol, especially long-chain fatty acids (LCFAs) and 2-oleoyl-glycerol (2-OG), but not medium-chain fatty acids (MCFAs). OBJECTIVE: We examined the impact of olive oil (20 mL) and its derivates, LCFAs and 2-OG, on enteroendocrine secretions [glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), peptide YY (PYY), and neurotensin (NT)] and on glucose, lipid, and bile acid metabolism in RYGB-operated and unoperated individuals. METHODS: In an exploratory randomized crossover design, 10 RYGB-operated patients and 10 matched controls ingested 3 equimolar triacylglycerol formulations on separate days: olive oil (digested to 2-OG + LCFAs), C8-dietary oil (2-OG + MCFAs), and tricaprylin (MCFAs; negative control). Hormone responses were calculated as area under the curve (AUC). RESULTS: Independent of group status, olive oil had greater effects than C8-dietary oil on AUCs of plasma GLP-1 (+32%; 95% CI: 23%, 43%; P < 0.01), CCK (+53%, P < 0.01), and NT (+71%, P < 0.01), whereas the effect on GIP differed between groups (+90% in controls, P < 0.01; +24% in RYGB, P = 0.10). Independent of group status, C8-dietary oil had greater effects than tricaprylin on AUCs of plasma CCK (+40%, P < 0.01) and NT (+32%, P < 0.01), but not GLP-1 (+5%; 95% CI: -2.9%, 13%; P = 0.22), whereas the effect on GIP again differed between groups (+78% in controls, P < 0.01; +39% in RYGB, P = 0.01). Distal (GLP-1/PYY/NT), but not proximal (CCK/GIP), enteroendocrine responses were generally greater in RYGB patients than in controls. CONCLUSIONS: The combination of LCFAs plus 2-OG was substantially more effective than 2-OG plus MCFAs in stimulating enteroendocrine secretion in RYGB-operated and matched control individuals. Distal lipid-induced gut hormone release was greater after RYGB.This trial was registered at clinicaltrials.gov as NCT03223389.