Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality

Alghamdi, Jahad; Alaamery, Manal; Barhoumi, Tlili; Rashid, Mamoon; Alajmi, Hala; Aljasser, Nasser; Alhendi, Yaseen; Alkhalaf, Hend; Alqahtani, Hanadi; Algablan, Omer; Alshaya, Abdulraham I.; Tashkandi, Nabiha; Massadeh, Salam; Almuzzaini, Bader; Ehaideb, Salleh N.; Bosaeed, Mohammad; Ayoub, Kamal; Yezli, Saber; Khan, Anas; Alaskar, Ahmed; Bouchama, Abderrezak

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population . We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01–2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16–4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype (P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.