ad194ea007e8eacefea7b1aa90e5e955 311690.pdf 8bd9d24e7898bed1763c134d4bfd52f14ddca6ee 311690.pdf e835d5e8e1b946215d14aa89ef25a88ec5ed0e31ee10d91951f95f013ddf0a3d 311690.pdf Title: MMS19 and IFIH1 Host Genetic Variants Associate with SARS-CoV-2 Infection in Elderly Residents of Long-TermCare Facilities Subject: 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. 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. 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). Our results indicate that MMS19/rs2236575_A and IFIH1/rs1990760_TC genetic variants were associated with a resistance to SARS-CoV-2 infection in a cohort of institutionalized seniors. Keywords: SARS-CoV-2; infection susceptibility; host genetics; elderly; COVID-19 Author: Sandra Franco, Macedonia Trigueros, Dolors Palacín, Josep Maria Bonet-Simó, Maria del Mar Isnard, Nemesio Moreno, Lourdes Mateu, Nuria Prat, Marta Massanella and Miguel Angel Martinez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Aug 7 12:59:02 2024 CEST ModDate: Wed Aug 7 13:01:40 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 8 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 257893 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YWWVQQ+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 JOIXPV+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 IABPSQ+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 DBEAYT+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 OGLZWV+VnURWPalladioL Type 1 Custom yes yes yes 32 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 65 0 SOSCBV+CMSY10 Type 1 Builtin yes yes yes 73 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-06-24 02:46:13 CEST RepresentationInformation: 311690.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-06-23 08:57:31 CEST Size: 257893 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 223 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Participants Destination: subsection.2.1 Item: Title: Ethics Destination: subsection.2.2 Item: Title: Single-Nucleotide Polymorphism Genotyping Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.5 Info: Title: MMS19 and IFIH1 Host Genetic Variants Associate with SARS-CoV-2 Infection in Elderly Residents of Long-TermCare Facilities Author: Sandra Franco, Macedonia Trigueros, Dolors Palacín, Josep Maria Bonet-Simó, Maria del Mar Isnard, Nemesio Moreno, Lourdes Mateu, Nuria Prat, Marta Massanella and Miguel Angel Martinez Subject: 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. 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. 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). Our results indicate that MMS19/rs2236575_A and IFIH1/rs1990760_TC genetic variants were associated with a resistance to SARS-CoV-2 infection in a cohort of institutionalized seniors. 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