1. BMC Nephrol. 2024 Dec 18;25(1):449. doi: 10.1186/s12882-024-03896-1.

Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial 
kidney disease due to MUC1 mutations: an observational study.

Kidd KO(1)(2), Williams AH(3), Taylor A(1), Martin L(1), Robins V(1), Sayer 
JA(4)(5)(6), Olinger E(7), Mabillard HR(4), Papagregoriou G(8), Deltas C(8), 
Stavrou C(9), Conlon PJ(10)(11), Hogan RE(10)(11), Elhassan EAE(10)(11), 
Springer D(12), Zima T(12), Izzi C(13), Vrbacká A(2), Piherová L(2), Pohludka 
M(14), Radina M(2), Vylet'al P(2), Hodanova K(2), Zivna M(1)(2), Kmoch 
S(1)(2)(15), Bleyer AJ Sr(16)(17).

Author information:
(1)Wake Forest School of Medicine, Section on Nephrology, Winston-Salem, NC, 
27157, USA.
(2)Department of Paediatrics and Inherited Metabolic Disorders, Research Unit of 
Rare Diseases, First Faculty of Medicine, Charles University, Prague, Czech 
Republic.
(3)DNA Data Solutions, LLC, St. Petersburg, FL, USA.
(4)Translational and Clinical Research Institute, Faculty of Medical Sciences, 
Newcastle University, Newcastle upon Tyne, UK.
(5)Renal Services, The Newcastle upon Tyne Hospitals NHS Foundation Trust, 
Newcastle upon Tyne, UK.
(6)Newcastle Biomedical Research Centre, NIHR, Newcastle upon Tyne, UK.
(7)Center for Human Genetics, Cliniques universitaires Saint-Luc, Brussels, 
Belgium.
(8)Department of Biological Sciences, Molecular Medicine Research Center, 
University of Cyprus, Nicosia, Cyprus.
(9)Department of Nephrology, Evangelismos Hospital, Paphos, Cyprus.
(10)Department of Nephrology and Transplantation Beaumont Hospital, Dublin, 
Ireland.
(11)Royal College of Surgeons in Ireland, Dublin, Ireland.
(12)Institute of Medical Biochemistry and Laboratory Diagnostics, General 
University Hospital and the First Faculty of Medicine of Charles University, 
Prague, Czech Republic.
(13)Clinical Genetics Unit, University of Brescia and Spedali Civili, Brescia, 
Italy.
(14)Genespector, Prague, Czech Republic.
(15)Medirex Group Academy, Trnava, Slovakia.
(16)Wake Forest School of Medicine, Section on Nephrology, Winston-Salem, NC, 
27157, USA. ableyer@wakehealth.edu.
(17)Department of Paediatrics and Inherited Metabolic Disorders, Research Unit 
of Rare Diseases, First Faculty of Medicine, Charles University, Prague, Czech 
Republic. ableyer@wakehealth.edu.

Update of
    medRxiv. 2024 Jul 04:2024.07.03.24309887. doi: 10.1101/2024.07.03.24309887.

BACKGROUND: MUC1 and UMOD pathogenic variants cause autosomal dominant 
tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal 
mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to 
haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal 
mucin-1.
METHODS: 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.
RESULTS: Surveys were emailed to 637 individuals, with responses from 89 
ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey 
respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD 
respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including 
additional familial cases reported from survey respondents, 10/41 (24%) 
ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 
9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to 
infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 
7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our 
longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 
individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). 
Multivariate logistic regression revealed the following odds ratios (95% 
confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9-29.5), kidney 
transplant 5.5 (1.6-9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 
(1.0-1.1).
CONCLUSIONS: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of 
COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of 
mucin-1 may be responsible.

© 2024. The Author(s).

DOI: 10.1186/s12882-024-03896-1
PMCID: PMC11654191
PMID: 39696072 [Indexed for MEDLINE]

Conflict of interest statement: Declarations. Ethics approval and consent to 
participate: This study was approved by the Wake Forest University Health 
Sciences Institutional Review Board, Winston-Salem, NC, United States, in 
accordance with the Declaration of Helsinki. All individuals presented in the 
study provided voluntary, autonomous consent to participate. Consent for 
publication: Not applicable. Competing interests: AJB has also received funding 
from the Black Brogan Foundation, The Slim Health Foundation, Soli Deo Gloria. 
He has received compensation as follows: advisory board, Horizon Pharma; 
speaker, Natera; author, UpToDate; advisor, First Faculty of Medicine, Charles 
University; royalty; patent for UMOD genetic diagnosis. PJC has received funding 
from Astra Zeneca, Bohringher, Hansa, and medical advisory board fees. KOK, AHW, 
AT, AK, LM, VR, APR-C, JAS, EO, HRM, GP, CD, CS, REH, EE, DS, CI, AV, LP, TZ, 
MP, MR, PV, KH, MZ, and SK have nothing to disclose.