MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil

• DOI: 10.3389/fimmu.2022.975918
• Publication Date: 2022-10-25T10:43:12Z
• Authors: Erick C. Castelli; Mateus V. de Castro; Michel S. Naslavsky; Marilia O. Scliar; Nayane S. B. Silva; Raphaela N. Pereira; Viviane A. O. Cir...; Camila F. B. Castro; Celso T. Mendes-J...; Etiele de S. Silv...; Iuri M. de Oliveira; Eduardo C. Antonio; Gustavo F. Vieira; Diogo Meyer; Kelly Nunes; Larissa R. B. Matos; Monize V. R. Silva; Jaqueline Y. T. Wang; Joyce Esposito; Vivian R. Cória; Jhosiene Y. Magawa; Keity S. Santos; Edecio Cunha-Neto; Jorge Kalil; Raul H. Bortolin; Mário Hiroyuki Hi...; Luiz P. Dell’Aquila; Alvaro Razuk-Filho; Pedro B. Batista-...; Amaro N. Duarte-Neto; Marisa Dolhnikoff; Paulo H. N. Saldiva; Maria Rita Passos...; Mayana Zatz
• Keywords: HLA-A

Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the genetic variants responsible increased disease susceptibility are associated immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes interleukins; chemokines receptors. On other hand, little is known about resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in MHC region Covid-19 outcome resilient patients as compared to younger severe outcome. infection was confirmed by RT-PCR test. Aiming identify candidate host resistance, investigated 87 older than 90 years who recovered from remained asymptomatic following positive test 55 60 had died due well general population same city. Whole-exome sequencing an in-depth analysis performed. All samples were collected early 2020 before local vaccination programs started. We found that group displayed higher frequency some missense MUC22 gene (a member mucins' family) one strongest signals control population. For example, variant rs62399430 at two times more frequent among (p = 0.00002, OR 2.24). Since pro-inflammatory basal state may enhance hypothesized might play important protective role reducing overactive responses senior