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Background: Seronegative coeliac disease is poorly defined. Aims:To study clinical phenotypes and long-term outcomes of seronegative coeliac disease in a multicentre cohort over 20 years.Methods: Seronegative coeliac disease was diagnosed in HLA-DQ2/DQ8-positive patients with villous atrophy (VA), negative IgA endomysial (EmA), tissue transglutaminase (tTG) and deamidated-gliadin antibodies (DGP), clinical and histological response to a gluten-free diet (GFD), and no alternative causes for VA. In patients with IgA deficiency, coeliac disease was diagnosed through VA, positive IgG EmA/tTG/ DGP and clinical/histological response to a GFD (coeliac disease+IgAd). Patients with seropositive coeliac disease served as controls.Results: Of 227 patients previously diagnosed with seronegative coeliac disease, true seronegative coeliac disease was confirmed in 84, coeliac disease+IgAd in 48, and excluded in 55. Lack of follow-up duodenal biopsy precluded diagnosing seronegative coeliac disease in 40 patients. 2084 patients with seropositive coeliac disease served as controls. True seronegative coeliac disease had more severe symptoms at diagnosis and a higher risk of complications (HR 10.87,, P < 0.001) and mortality (HR 2.18, 95% CI 1.12-4.26, P < 0.01) than seropositive coeliac disease.There were no differences between true seronegative coeliac disease and coeliac disease+IgAd. On multivariate analysis, age at diagnosis, lack of clinical response to a GFD, true seronegative coeliac disease, coeliac disease+IgAd, and classical presentation predicted complications. Age at diagnosis, complications and absence of clinical response to a GFD predicted mortality. Conclusions:Seronegative coeliac disease has a more aggressive disease phenotype than seropositive coeliac disease. These data argue against over-reliance on serology for the diagnosis of coeliac disease and support a strict clinical and histologic followup in seronegative coeliac disease.

Objectives Data on SARS-CoV-2 disease (COVID-19) in adult coeliac disease (CD) are lacking. The aim of the present study is to evaluate the epidemiology and clinical features of COVID-19 in adult coeliac patients regularly followed-up at our centre since January 2015. Methods Data about general health status and clinical features of laboratory-confirmed COVID-19 were prospectively collected over the phone. Data about CD were retrospectively collected from clinical notes. Prevalence and incidence of COVID-19 were compared between the coeliac cohort and the figures in the general population of Lombardy, Northern Italy between 20 February to 5 June 2020 provided by the Italian National Institute of Health (Istituto Superiore di Sanità) and the Lombardy regional government. Results Nine out of 324 patients contracted COVID-19, thus resulting in a prevalence of 2.78% [95% confidence interval (CI) 0.98–4.58] and an incidence rate of 8.15/1000 person-month (95% CI 4.24–15.66). Prevalence of COVID-19 ascertained by means of nasal swab was 1.79% (95% CI 0.22–3.35) and the incidence rate 5.26/1000 person-month (95% CI 2.19–12.63), without difference from the general population. Clinical type of CD, age, sex, duration and adherence to a gluten-free diet, and mucosal healing did not differ between coeliac patients with and without COVID-19. None of the 9 patients with COVID-19 required hospitalization. Conclusion Patients with CD do not seem to carry an increased risk of COVID-19 compared to the general population and their disease course is mild.