tetano
Editor, Senior Moderator
Sci Rep
. 2025 Jul 2;15(1):23074.
doi: 10.1038/s41598-025-08416-1. Rare genetic variants and severe COVID-19 in previously healthy admixed Latin American adults
Gabriela Dias Rocha[SUP] #[/SUP][SUP] 1 2 [/SUP], Pablo Rafael Silveira Oliveira[SUP] #[/SUP][SUP] 3 [/SUP], Marcus Villander Barros de Oliveira Sá[SUP] 4 5 [/SUP], Túlio de Lima Campos[SUP] 4 [/SUP], Steffany Larissa Galdino Galisa[SUP] 4 [/SUP], Andreia Soares Silva[SUP] 6 [/SUP], Patricia Moura[SUP] 1 [/SUP], Raquel Bispo de São Pedro[SUP] 3 [/SUP], Natália Machado Tavares[SUP] 7 [/SUP], Viviane Sampaio Boaventura[SUP] 7 [/SUP], Sara Nunes[SUP] 7 [/SUP], Icaro Bonyek-Silva[SUP] 8 [/SUP], Juliana Ribeiro Caldas[SUP] 9 [/SUP], Eric Henrique Roma[SUP] 10 [/SUP], Jorge Reis Almeida[SUP] 11 [/SUP], Andrea Alice Silva[SUP] 11 [/SUP], Tatiana Baccin[SUP] 12 [/SUP], Andrea Cauduro de Castro[SUP] 12 [/SUP], Antônio Carlos Rosario Vallinoto[SUP] 13 [/SUP], Rosilene da Silva[SUP] 14 [/SUP], Eduardo José Melo Dos Santos[SUP] 14 [/SUP], Cristiana Couto Garcia[SUP] 15 16 [/SUP], Renata Dezengrini Slhessarenko[SUP] 17 [/SUP], Anderson da Costa Armstrong[SUP] 2 [/SUP], Rodrigo Feliciano do Carmo[SUP] #[/SUP][SUP] 18 19 20 [/SUP], Luydson Richardson Silva Vasconcelos[SUP] #[/SUP][SUP] 21 22 [/SUP]
Affiliations
Rare genetic variants that affect host defense against SARS-CoV-2 may contribute to COVID-19 progression, helping to explain severe or fatal cases in young and middle-aged patients. This study aimed to identify rare genetic variants potentially implicated in life-threatening COVID-19 in a cohort of Brazilian patients aged 18 to 60, with no prior history of health issues, who required intensive care unit admission (n = 161). Whole genome sequencing was performed, followed by a prioritization approach for rare variants in loci previously associated with severe COVID-19. A total of 104 rare and potentially deleterious variants were identified in 79 genes. Ultra-rare variants in MUC5AC, IFNA10, ZNF778, and PTOV1 were the most frequently observed. We report 17 novel variants, including those likely pathogenic or indicating strong loss-of-function (LoF) intolerance. Patients carrying prioritized rare variants had a significantly higher incidence of acute respiratory distress syndrome (ARDS) (p = 0.027, OR = 2.59). Additionally, patients with variants in highly LoF-intolerant genes had a fourfold higher risk of death (p = 0.0084, OR = 4.04). To date, this is the first genomic analysis of previously healthy young and middle-aged Latin American patients with severe COVID-19. Our findings highlight the importance of identifying population-specific genetic risk factors.
Keywords: COVID-19; Rare variants; SARS-CoV-2; Severity; Whole genome sequencing.
. 2025 Jul 2;15(1):23074.
doi: 10.1038/s41598-025-08416-1. Rare genetic variants and severe COVID-19 in previously healthy admixed Latin American adults
Gabriela Dias Rocha[SUP] #[/SUP][SUP] 1 2 [/SUP], Pablo Rafael Silveira Oliveira[SUP] #[/SUP][SUP] 3 [/SUP], Marcus Villander Barros de Oliveira Sá[SUP] 4 5 [/SUP], Túlio de Lima Campos[SUP] 4 [/SUP], Steffany Larissa Galdino Galisa[SUP] 4 [/SUP], Andreia Soares Silva[SUP] 6 [/SUP], Patricia Moura[SUP] 1 [/SUP], Raquel Bispo de São Pedro[SUP] 3 [/SUP], Natália Machado Tavares[SUP] 7 [/SUP], Viviane Sampaio Boaventura[SUP] 7 [/SUP], Sara Nunes[SUP] 7 [/SUP], Icaro Bonyek-Silva[SUP] 8 [/SUP], Juliana Ribeiro Caldas[SUP] 9 [/SUP], Eric Henrique Roma[SUP] 10 [/SUP], Jorge Reis Almeida[SUP] 11 [/SUP], Andrea Alice Silva[SUP] 11 [/SUP], Tatiana Baccin[SUP] 12 [/SUP], Andrea Cauduro de Castro[SUP] 12 [/SUP], Antônio Carlos Rosario Vallinoto[SUP] 13 [/SUP], Rosilene da Silva[SUP] 14 [/SUP], Eduardo José Melo Dos Santos[SUP] 14 [/SUP], Cristiana Couto Garcia[SUP] 15 16 [/SUP], Renata Dezengrini Slhessarenko[SUP] 17 [/SUP], Anderson da Costa Armstrong[SUP] 2 [/SUP], Rodrigo Feliciano do Carmo[SUP] #[/SUP][SUP] 18 19 20 [/SUP], Luydson Richardson Silva Vasconcelos[SUP] #[/SUP][SUP] 21 22 [/SUP]
Affiliations
- PMID: 40595275
- PMCID: PMC12218055
- DOI: 10.1038/s41598-025-08416-1
Rare genetic variants that affect host defense against SARS-CoV-2 may contribute to COVID-19 progression, helping to explain severe or fatal cases in young and middle-aged patients. This study aimed to identify rare genetic variants potentially implicated in life-threatening COVID-19 in a cohort of Brazilian patients aged 18 to 60, with no prior history of health issues, who required intensive care unit admission (n = 161). Whole genome sequencing was performed, followed by a prioritization approach for rare variants in loci previously associated with severe COVID-19. A total of 104 rare and potentially deleterious variants were identified in 79 genes. Ultra-rare variants in MUC5AC, IFNA10, ZNF778, and PTOV1 were the most frequently observed. We report 17 novel variants, including those likely pathogenic or indicating strong loss-of-function (LoF) intolerance. Patients carrying prioritized rare variants had a significantly higher incidence of acute respiratory distress syndrome (ARDS) (p = 0.027, OR = 2.59). Additionally, patients with variants in highly LoF-intolerant genes had a fourfold higher risk of death (p = 0.0084, OR = 4.04). To date, this is the first genomic analysis of previously healthy young and middle-aged Latin American patients with severe COVID-19. Our findings highlight the importance of identifying population-specific genetic risk factors.
Keywords: COVID-19; Rare variants; SARS-CoV-2; Severity; Whole genome sequencing.