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1. Additional file 1 of Use of glucagon in severe hypoglycemia is scarce in most countries, and has not been expanded by new ready-to-use glucagons

Author

Pontiroli, Antonio E., Rizzo, Manfredi, and Tagliabue, Elena

Abstract

Additional file 1: Table S1. Persons with diabetes per country in various years. Table S2. Persons with type 1 diabetes per country in various years. Absolute prevalence. Table S3. Glucagon sales (any type, millions of units) in 2019-2021 in countries where new ready-to-use glucagons were or were not available in 2019-2021. Only retail data are considered. Totals and mean ± SD are reported. On the left: sales in countries where new drugs were (Group A) or were not (Group B) available in 2019-2021. On the right: sales in the same countries when new drugs are not considered. Table S4. Glucagon units (any type) by country. Totals and mean ± SD. Retail and hospital sales are considered together. Table S5. Commercial sales of glucagon formulations (any type) by country. Retail and hospital sales are considered together. Figure S1. Persons with type 1 diabetes and glucagon sales (any type, millions of units) in years 2014-2019.Figure S2. Persons with type 1 diabetes and glucagon sales (any type, millions of units) in year 2021; comparison between data on prevalence of type 1 diabetes according to IDF Atlas and to the recent paper (Lancet Diabetes Endocrinol 2022; 10:741).

Published
2023
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2. The interferon landscape along the respiratory tract impacts the severity of COVID-19

Author

Riccardo Colombo, Ivan Zanoni, Andreas Wack, Achille Broggi, Nicola Clementi, Tommaso Fossali, Laura Marongiu, Elena Tagliabue, Andrea Bottazzi, Fabio A. Facchini, Sofia Sisti, Janet Chou, Roberto Spreafico, Roberto Ferrarese, Elena Criscuolo, Vanessa Frangipane, Jaclyn M. Long, Federica Meloni, Nicasio Mancini, Sara Bozzini, Stefania Crotta, Benedetta Sposito, Massimo Clementi, Enju Liu, Antonio E. Pontiroli, Laura Pandolfi, Alessandro Ambrosi, Laura Saracino, Harvard Medical School [Boston] (HMS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Pavia = University of Pavia (UNIPV), The Francis Crick Institute [London], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Institute for Quantitative and Computational Biosciences - University of california LA, Division of Gastroenterology [Boston, MA, USA], Harvard University-Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Center [Boston] (BIDMC), Dipartimento di Informatica, Matematica, Elettronica e Trasporti [Reggio Calabria] (DIMET), Universita Mediterranea of Reggio Calabria [Reggio Calabria], Luigi sacco hospital - Division of Anesthesiology and intensive Care, IRCCS Multimedica, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Università degli Studi di Milano = University of Milan (UNIMI), Division of Respiratory Diseases (IRCCS), Università degli Studi di Pavia = University of Pavia (UNIPV)-San Matteo' Hospital, IRCCS laboratory of medical microbiology and virology Milan, Harvard University [Cambridge]-Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Center [Boston] (BIDMC), DUMENIL, Anita, Sposito, B, Broggi, A, Pandolfi, L, Crotta, S, Clementi, N, Ferrarese, R, Sisti, S, Criscuolo, E, Spreafico, R, Long, J, Ambrosi, A, Liu, E, Frangipane, V, Saracino, L, Bozzini, S, Marongiu, L, Facchini, F, Bottazzi, A, Fossali, T, Colombo, R, Clementi, M, Tagliabue, E, Chou, J, Pontiroli, A, Meloni, F, Wack, A, Mancini, N, Zanoni, I, Sposito, Benedetta, Broggi, Achille, Pandolfi, Laura, Crotta, Stefania, Clementi, Nicola, Ferrarese, Roberto, Sisti, Sofia, Criscuolo, Elena, Spreafico, Roberto, Long, Jaclyn M., Ambrosi, Alessandro, Liu, Enju, Frangipane, Vanessa, Saracino, Laura, Bozzini, Sara, Marongiu, Laura, Facchini, Fabio A., Bottazzi, Andrea, Fossali, Tommaso, Colombo, Riccardo, Clementi, Massimo, Tagliabue, Elena, Chou, Janet, Pontiroli, Antonio E., Meloni, Federica, Wack, Andrea, Mancini, Nicasio, and Zanoni, Ivan

Subjects
Model organisms, Aging, dendritic cell, pattern recognition receptor, [SDV]Life Sciences [q-bio], Respiratory System, Immunology, Type I IFN, Infectious Disease, Biology, Severity of Illness Index, Article, General Biochemistry, Genetics and Molecular Biology, lung, Interferon, Type III IFN, Severity of illness, Leukocytes, medicine, Humans, Respiratory system, ComputingMilieux_MISCELLANEOUS, Regulation of gene expression, Respiratory Distress Syndrome, Human Biology & Physiology, Lung, SARS-CoV-2, epithelial cell, FOS: Clinical medicine, Age Factors, Pattern recognition receptor, COVID-19, Epithelial Cells, interferon, Viral Load, COVID-19, SARS-CoV-2, Type I IFN, Type III IFN, airways, dendritic cell, epithelial cell, interferon, lung, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Gene Expression Regulation, airways, airway, Interferons, Viral load, Respiratory tract, medicine.drug
Abstract

Severe COVID-19 is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members, denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against SARS-CoV-2. In contrast, compared to subjects with other infectious or non-infectious lung pathologies, IFNs are over-represented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites., An in-depth analysis of interferons in COVID-19 reveals differences in their roles based on anatomical location, viral load, age and disease severity. In the upper respiratory tract, high levels of IFN-III are protective and result in mild disease in spite of higher SARS-CoV-2 viral burden while the lower airways of patients with severe COVID-19 demonstrate elevated IFN-I and III, cell death and a reduction in interferon stimulated genes.

Published
2021
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