{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:56:46Z","timestamp":1768568206102,"version":"3.49.0"},"posted":{"date-parts":[[2024,7,4]]},"group-title":"Genetic and Genomic Medicine","reference-count":38,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    <jats:italic>MUC1<\/jats:italic>\n                    and\n                    <jats:italic>UMOD<\/jats:italic>\n                    pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD).\n                    <jats:italic>MUC1<\/jats:italic>\n                    is expressed in kidney, nasal mucosa and respiratory tract, while\n                    <jats:italic>UMOD<\/jats:italic>\n                    is expressed only in kidney. Due to haplo-insufficiency ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    patients produce approximately 50% of normal mucin-1.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Surveys were emailed to 637 individuals, with responses from 89 ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    and 132 ADTKD-\n                    <jats:italic>UMOD<\/jats:italic>\n                    individuals. 19\/83 (23%) ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    survey respondents reported a prior COVID-19 infection vs. 14\/125 (11%) ADTKD-\n                    <jats:italic>UMOD<\/jats:italic>\n                    respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0260). Including additional familial cases reported from survey respondents, 10\/41 (24%) ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    individuals died of COVID-19 vs. 1\/30 (3%) with ADTKD-\n                    <jats:italic>UMOD<\/jats:italic>\n                    , with OR 9.21 (95%CI 1.22-69.32),\n                    <jats:italic>P<\/jats:italic>\n                    = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    individuals was 7.06\u00b14.12 vs. 10.21\u00b14.02 U\/mL (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    individuals (5%) vs. 3 deaths in 478 ADTKD-\n                    <jats:italic>UMOD<\/jats:italic>\n                    individuals (0.6%) (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Individuals with ADTKD-\n                    <jats:italic>MUC1<\/jats:italic>\n                    are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-\n                    <jats:italic>UMOD<\/jats:italic>\n                    individuals. Haplo-insufficient production of mucin-1 may be responsible.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.07.03.24309887","type":"posted-content","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T13:10:18Z","timestamp":1720098618000},"source":"Crossref","is-referenced-by-count":0,"title":["Eight-Fold Increased COVID-19 Mortality in Autosomal Dominant Tubulointerstitial Kidney Disease due to\n                  <i>MUC1<\/i>\n                  Mutations: An Observational Study"],"prefix":"10.64898","author":[{"given":"Kendrah O.","family":"Kidd","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienne H.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbigail","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Robins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Sayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Olinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly R.","family":"Mabillard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Papagregoriou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantinos","family":"Deltas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoforos","family":"Stavrou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Conlon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard Edmund","family":"Hogan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elhussein A.E.","family":"Elhassan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drahom\u00edra","family":"Springer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1\u0161","family":"Zima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Izzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Vrback\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenka","family":"Piherov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Pohludka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Radina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Vylet\u2019al","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Hodanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Zivna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislav","family":"Kmoch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Sr.","given":"Anthony J.","family":"Bleyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024070723351311000_2024.07.03.24309887v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2014-z"},{"key":"2024070723351311000_2024.07.03.24309887v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-02242-x"},{"key":"2024070723351311000_2024.07.03.24309887v1.3","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0149-2020"},{"key":"2024070723351311000_2024.07.03.24309887v1.4","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2021.5248"},{"key":"2024070723351311000_2024.07.03.24309887v1.5","doi-asserted-by":"crossref","unstructured":"Kirby A , Gnirke A , Jaffe DB , et al. 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