{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:21:33Z","timestamp":1785424893777,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy of Craiova"},{"id":[{"id":"https:\/\/ror.org\/031d5vw30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The disproportionately severe disease course of diabetic patients with SARS-CoV-2 infection was repeatedly observed by clinicians during the COVID-19 pandemic. The overlap between metabolic impairment, viral pathophysiology, and chronic inflammation created a pattern that urged deeper examination. The aim of this paper was to review and synthesize evidence regarding the interaction between diabetes mellitus and COVID-19. We synthesized evidence across mechanistic pathways (immune dysregulation, chronic inflammation, ACE2\/DPP-4-related signaling, endothelial dysfunction, and pancreatic involvement) and key clinical outcomes (severity, intensive care unit (ICU) admission, mortality, dysglycaemia\/new-onset diabetes, and DKA). This systematic search was conducted in PubMed, Clinical Key, and Google Scholar. The eligibility criteria included papers on adults (\u226518 years) with pre-existing diabetes mellitus (type 1 or type 2) or newly diagnosed diabetes\/hyperglycemia and confirmed SARS-CoV-2 infection, published between January 2020 and October 2025, in English language. The PRISMA guidelines were used for data extraction. We identified 412 articles, out of which only 30 met all the inclusion criteria. Diabetes was consistently evoked as a major risk factor for severe COVID-19, being associated with higher susceptibility to pneumonia, respiratory failure, ICU admission, and mortality. The explanation lies in the impaired immune system, endothelial dysfunction, and metabolic repercussions imposed by hyperglycemia. Several antidiabetic drugs appeared protective in multiple cohorts. In conclusion, the accumulated evidence underscores the tight interplay between metabolic disease and COVID-19. Essentially, the clinical management of these patients would be a thoughtful selection of antidiabetic therapy and close metabolic monitoring.<\/jats:p>","DOI":"10.3390\/ijms27083537","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:56:56Z","timestamp":1776268616000},"page":"3537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetes Mellitus and COVID-19 in Adults: A Systematic Review of Pathophysiological Connections, Clinical Outcomes, and Therapeutic Considerations"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5127-5774","authenticated-orcid":false,"given":"Ioana-Madalina","family":"Mosteanu","sequence":"first","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"Institute of Pneumophtisiology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana-Andreea","family":"Parliteanu","sequence":"additional","affiliation":[{"name":"Institute of Pneumophtisiology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-922X","authenticated-orcid":false,"given":"Beatrice","family":"Mahler","sequence":"additional","affiliation":[{"name":"Institute of Pneumophtisiology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"},{"name":"Pneumology II Department, Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina","family":"Mitrea","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Clenciu","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-3617","authenticated-orcid":false,"given":"Adela Gabriela","family":"Stefan","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Calafat Municipal Hospital, 205200 Calafat, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Cristina Protasiewicz","family":"Timofticiuc","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Midwives and Nursing, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Stoichita","sequence":"additional","affiliation":[{"name":"Institute of Pneumophtisiology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"},{"name":"Pneumology II Department, Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela Simona","family":"Popoviciu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3116-8151","authenticated-orcid":false,"given":"Delia Viola","family":"Reurean Pintilei","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical and Complementary Sciences, Faculty of Medicine and Biological Sciences, \u201cStefan cel Mare\u201d University, 720229 Suceava, Romania"},{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Consultmed Medical Centre, 700544 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Magdalena","family":"Rosu","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Midwives and Nursing, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora Claudia","family":"Radu Gheonea","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice Elena","family":"Vladu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4817-1365","authenticated-orcid":false,"given":"Lidia","family":"Boldeanu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Mota","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8563-347X","authenticated-orcid":false,"given":"Ion Cristian","family":"Efrem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2014Medical Semiology, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6133-4341","authenticated-orcid":false,"given":"Ionela Mihaela","family":"Vladu","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mota","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-med-042220-011857","article-title":"COVID-19 and Diabetes","volume":"73","author":"Singh","year":"2022","journal-title":"Annu Rev 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