MMS19 and IFIH1 Host genetic variants associate with SARS-CoV-2 infection in elderly residents of long-term care facilities

Background: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults.
Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here,
we aimed to identify host genetic factors influencing the susceptibility to severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) infection

Methods: We genotyped 12 single-nucleotide polymorphisms
(SNPs) previously associated with the innate immune response in a total of 97 elderly (age > 65 years)
residents of three long-term care facilities located in Barcelona, Spain. Individuals were PCR-tested
during the SARS-CoV-2 outbreaks between September and November 2020

Results: SARS-CoV-2 PCR tests
revealed infections in 81 residents. Importantly, the 16 uninfected residents remained SARS-CoV-2
seronegative until vaccination (January and February 2021). After adjusting for sex and age, we
found that two SNPs were significantly associated with SARS-CoV-2 infection susceptibility—MMS19
nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) and interferon-induced
helicase C domain-containing 1 (IFIH1)/rs1990760 (p = 0.034). No association with SARS-CoV-2
infection was found for 10 additional genotyped SNPs, which included 4 SNPs on chromosome 12 in
the gene encoding oligoadenylate synthetase (OAS).

Conclusion: SARS-CoV-2 PCR tests
revealed infections in 81 residents. Importantly, the 16 uninfected residents remained SARS-CoV-2
seronegative until vaccination (January and February 2021). After adjusting for sex and age, we
found that two SNPs were significantly associated with SARS-CoV-2 infection susceptibility—MMS19
nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) and interferon-induced
helicase C domain-containing 1 (IFIH1)/rs1990760 (p = 0.034). No association with SARS-CoV-2
infection was found for 10 additional genotyped SNPs, which included 4 SNPs on chromosome 12 in
the gene encoding oligoadenylate synthetase (OAS).