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J Inflamm Res ; 14: 5187-5200, 2021.
Article in English | MEDLINE | ID: covidwho-1470718


Down syndrome (DS) is a unique genetic disease caused by the presence of an extra copy of chromosome 21, which carries four of the six interferon receptor (IFN-R) genes on its long arm. Recent studies reporting higher levels of interferon-stimulated gene (ISG) expression in primary immune cells studied ex vivo have suggested that the additional copies of the IFN-R genes in DS result in mild interferonopathy. In this review, we analyze the potential clinical and immunological impacts of this interferonopathy in DS. We performed a literature review to explore the epidemiology and risks of celiac disease, type 1 diabetes, thyroid dysfunction, mucocutaneous manifestations, infectious diseases (including COVID-19), and Alzheimer's disease in individuals with DS relative to the general population with or without iatrogenic exposure to interferons. We analyzed immunophenotyping data and the current experimental evidence concerning IFN-R expression, constitutive JAK-STAT activation, and ISG overexpression in DS. Despite the lack of direct evidence that implicating this mild interferonopathy directly in illnesses in individuals with DS, we highlight the challenges ahead and directions that could be taken to determine more clearly the biological impact of interferonopathy on various immune-related conditions in DS.

Gastroenterology ; 161(1): 360-361, 2021 07.
Article in English | MEDLINE | ID: covidwho-1331406
Gastroenterology ; 161(1): 360-361, 2021 07.
Article in English | MEDLINE | ID: covidwho-1294518
Gastroenterology ; 161(1): 360-361, 2021 07.
Article in English | MEDLINE | ID: covidwho-1246434
Gastroenterology ; 160(5): 1900-1901, 2021 04.
Article in English | MEDLINE | ID: covidwho-1189303
Gut ; 69(9): 1592-1597, 2020 09.
Article in English | MEDLINE | ID: covidwho-536627


OBJECTIVE: Treatment options for non-hospitalised patients with coronavirus disease 2019 (COVID-19) to reduce morbidity, mortality and spread of the disease are an urgent global need. The over-the-counter histamine-2 receptor antagonist famotidine is a putative therapy for COVID-19. We quantitively assessed longitudinal changes in patient reported outcome measures in non-hospitalised patients with COVID-19 who self-administered high-dose famotidine orally. DESIGN: Patients were enrolled consecutively after signing written informed consent. Data on demographics, COVID-19 diagnosis, famotidine use, drug-related side effects, temperature measurements, oxygen saturations and symptom scores were obtained using questionnaires and telephone interviews. Based on a National Institute of Health (NIH)-endorsed Protocol to research Patient Experience of COVID-19, we collected longitudinal severity scores of five symptoms (cough, shortness of breath, fatigue, headaches and anosmia) and general unwellness on a four-point ordinal scale modelled on performance status scoring. All data are reported at the patient level. Longitudinal combined normalised symptom scores were statistically compared. RESULTS: Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5-21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased. CONCLUSIONS: The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19.

Coronavirus Infections , Drug Monitoring/methods , Famotidine/administration & dosage , Pandemics , Pneumonia, Viral , Symptom Assessment/methods , Adult , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Dose-Response Relationship, Drug , Female , Histamine H2 Antagonists/administration & dosage , Humans , Male , Middle Aged , Oximetry/methods , Patient Reported Outcome Measures , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Retrospective Studies , SARS-CoV-2 , Self Administration , Treatment Outcome