{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:52:21Z","timestamp":1785430341000,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202107720033"],"award-info":[{"award-number":["202107720033"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"award":["202107720033"],"award-info":[{"award-number":["202107720033"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002999","name":"Dutch Ministry of Health, Welfare and Sport","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002999","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/041evnj42","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Dutch Ministry of Economic Affairs"},{"id":[{"id":"https:\/\/ror.org\/00bc6bw85","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005075","name":"University Medical Center Groningen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005075","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03cv38k47","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Groningen University"},{"id":[{"id":"https:\/\/ror.org\/012p63287","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Provinces in the North of the Netherlands"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The rapid emergence of immune-evasive SARS-CoV-2 variants necessitates the identification of accessible, low-cost prophylactic strategies. While drug repurposing offers a time-efficient alternative to novel drug development, clinical evidence for existing medications in the general population remains limited. The PharmLines Initiative provided us with unique data linkage for this study to assess the associations between 42 candidate drugs and COVID-19 infection. Potential effect modification by dominant SARS-CoV-2 strain and COVID-19 vaccination status was addressed. Methods: We conducted a test-negative case\u2013control study using data from the Lifelines cohort and University of Groningen IADB.nl dispensing database. Cases were adults with self-reported reverse transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 and controls had only negative results. Cases and controls were matched in age, sex, and testing date. The 42 candidate drugs were identified through a systematic review of prior publications. The primary outcome was SARS-CoV-2 infection. We applied multivariable conditional logistic regression to estimate the associations, with subgroup analyses for variant and vaccination effects. Significance levels were corrected for multiple testing. Results: From November 2020 to October 2022, we included 2019 test-positive cases and 4089 matched test-negative controls with a mean age of 57 years and 67% female. After adjustments for confounders, none of the studied drugs were associated with SARS-CoV-2 infection. When stratified by SARS-CoV-2 variants, chronic use of calcium channel blockers (adjusted odds ratio 2.13; 95% CI 1.45\u20133.13), diuretics (2.23; 95% CI 1.50\u20133.32), and metformin (4.31; 95% CI 1.91\u20139.69) were associated with increased risks of original strain SARS-CoV-2 infection. No significant associations were found in the vaccination status subgroup analysis. Conclusions: Despite limited statistical power for some drugs, none of the studied drugs showed protective associations against SARS-CoV-2 infection. Antihypertensives and metformin were associated with increased risk. These findings do not support the off-label use of these drugs as COVID-19 prophylaxis in the general population.<\/jats:p>","DOI":"10.3390\/ph19060861","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:08:02Z","timestamp":1780535282000},"page":"861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing Candidate Drugs to Prevent SARS-CoV-2: A PharmLines Test-Negative Case\u2013Control Study"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1872-0084","authenticated-orcid":false,"given":"Guiling","family":"Zhou","sequence":"first","affiliation":[{"name":"Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Dael","sequence":"additional","affiliation":[{"name":"Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Verweij","sequence":"additional","affiliation":[{"name":"Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Dutch Medicines Evaluation Board, 3503 RG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1590-2093","authenticated-orcid":false,"given":"Spyros","family":"Balafas","sequence":"additional","affiliation":[{"name":"Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-1061","authenticated-orcid":false,"given":"Sumaira","family":"Mubarik","sequence":"additional","affiliation":[{"name":"Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Bos","sequence":"additional","affiliation":[{"name":"Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria Gerdina","family":"Pasmooij","sequence":"additional","affiliation":[{"name":"Dutch Medicines Evaluation Board, 3503 RG Utrecht, The Netherlands"},{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3508 TB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"van Baarle","sequence":"additional","affiliation":[{"name":"Virology and Immunology Research Group, Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G. M.","family":"Mol","sequence":"additional","affiliation":[{"name":"Dutch Medicines Evaluation Board, 3503 RG Utrecht, The Netherlands"},{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-4471","authenticated-orcid":false,"given":"Geertruida H.","family":"de Bock","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eelko","family":"Hak","sequence":"additional","affiliation":[{"name":"Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Lifelines Corona Research Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e326","DOI":"10.1016\/S2214-109X(21)00593-3","article-title":"Response to Additional COVID-19 Vaccine Doses in People Who Are Immunocompromised: A Rapid Review","volume":"10","author":"Parker","year":"2022","journal-title":"Lancet Glob. 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