Am J Respir Crit Care Med. 2022 Jun 30. doi: 10.1164/rccm.202109-2166OC. Online ahead of print.
ABSTRACT
RATIONALE: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in SARS-CoV-2 infection and disease severity is unclear.
OBJECTIVES: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with COVID-19 infection among participants in the Million Veteran Program (MVP).
METHODS: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by trans-ancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (BMI, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects.
MEASUREMENTS AND MAIN RESULTS: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations (Ncases=4,325/, Ncontrols=507,640; OR=0.89 [0.82-0.97], p=6.86 x 10-03) in trans-ancestry meta-analysis within MVP and joint meta-analyses with the HGI (Ncases=13,320, Ncontrols=1,508,841; OR=0.90 [0.86-0.95], p =8.99 x 10-05). The rs35705950-T allele was not associated reduced COVID-19 positivity in trans-ancestry meta-analysis within MVP (Ncases=19,168/Ncontrols=492,854; OR=0.98 [0.95-1.01], p=0.06) but was nominally significant (p<0.05) in the joint meta-analysis with HGI (Ncases=44,820/Ncontrols=1,775,827; OR=0.97 [0.95-1]; p=0.03). We did not observe associations with severe outcomes or mortality. Among MVP individuals of European ancestry, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR=0.82 [0.72-0.93], p=0.001).
CONCLUSIONS: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PMID:35771531 | DOI:10.1164/rccm.202109-2166OC
