The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

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SummaryBackgroundA major deficit in understanding and improving treatment in coeliac disease (CD) is the lack of empiric data on real world gluten exposure.AimsTo estimate gluten exposure on a gluten‐free diet (GFD) using immunoassays for gluten immunogenic peptides (GIP) and to examine relationships among GIP detection, symptoms and suspected gluten exposuresMethodsAdults with biopsy‐confirmed CD on a GFD for 24 months were recruited from a population‐based inception cohort. Participants kept a diary and collected urine samples for 10 days and stools on days 4‐10. ‘Doggie bags’ containing ¼ portions of foods consumed were saved during the first 7 days. Gluten in food, stool and urine was quantified using A1/G12 ELISA.ResultsEighteen participants with CD (12 female; age 21‐70 years) and three participants on a gluten‐containing diet enrolled and completed the study. Twelve out of 18 CD participants had a median 2.1 mg gluten per exposure (range 0.2 to >80 mg). Most exposures were asymptomatic and unsuspected. There was high intra‐individual variability in the interval between gluten ingestion and excretion. Participants were generally unable to identify the food.ConclusionsGluten exposure on a GFD is common, intermittent, and usually silent. Excretion kinetics are highly variable among individuals. The amount of gluten varied widely, but was typically in the milligram range, which was 10‐100 times less than consumed by those on an unrestricted diet. These findings suggest that a strict GFD is difficult to attain, and specific exposures are difficult to detect due to variable time course of excretion.

BACKGROUND A gluten-free diet is the only recommended treatment for coeliac disease. AIM To determine the prevalence and characteristics of reactions to gluten among persons with coeliac disease on a gluten-free diet. METHODS Adults with biopsy proven, newly diagnosed coeliac disease were prospectively enrolled. A survey related to diet adherence and reactions to gluten was completed at study entry and 6 months. The Celiac Symptom Index (CSI), Celiac Diet Assessment Tool (CDAT) and Gluten-Free Eating Assessment Tool (GF-EAT) were used to measure coeliac disease symptoms and gluten-free diet adherence. RESULTS Of the 105 participants, 91% reported gluten exposure <1 per month and median CDAT score was 9 (IQR 8-11), consistent with adequate adherence. A suspected symptomatic reaction to gluten was reported by 66%. Gluten consumption was unsuspected until a reaction occurred (63%) or resulted from problems ordering in a restaurant (29%). The amount of gluten consumed ranged from cross-contact (30%) to a major ingredient (10%). Median time to symptom onset was 1 hour (range 10 min to 48 h), and median symptom duration was 24h (range 1 h to 8 days). Common symptoms included abdominal pain (80%), diarrhea (52%), fatigue (33%), headache (30%) and irritability (29%). CONCLUSION Reactions to suspected gluten exposure are common among patients with coeliac disease on a gluten-free diet. Eating at restaurants and other peoples’ homes remain a risk for unintentional gluten exposure. When following individuals with coeliac disease, clinicians should include questions regarding reactions to gluten as part of their assessment of gluten-free diet adherence.