Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19

Cordero, Ana I Hernández; Li, Xuan; Milne, Stephen; Yang, Chen Xi; Bossé, Yohan; Joubert, Philippe; Timens, Wim; Berge, Maarten van den; Nickle, David C.; Hao, Ke; Sin, Don D.

doi:10.1007/s00439-021-02264-5

Cited by 38 publications

(27 citation statements)

References 47 publications

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“…The Zika virus (ZIKV) infection of A549 cells induces OAS2 expression that inhibits ZIKV replication through enhanced IFNβ expression, which leads to the induction of the Jak/STAT signaling pathway ( Liao et al, 2020 ). Association of critical COVID-19 with rs10735079 in the OAS1-3 gene cluster was reported for a sample of mostly European ancestry in a recent GWAS ( Pairo-Castineira et al, 2020 ) and increased levels of OAS1 decreases the susceptibility to COVID-19 and, in particular, severe COVID-19 ( Hernández-Cordero et al, 2021 ). The splice-site variant rs10774671*G in the gene OAS1 is associated with greater OAS1 expression and has strong alternative splicing quantitative trait loci (asQTL) effect on OAS1 ( Sams et al, 2016 ) that results in higher levels of the p46 isoform and reduced COVID-19 susceptibility and severity ( Zhou et al, 2021 ).…”

Section: Host Genetics Beyond Hla and Kirmentioning

confidence: 90%

“…In COVID-19, ARDS, AKI, and hemostasis alteration have also been reported ( Wu et al, 2020 , McIntosh, 2020 ). The analysis by a multi-omics approach suggested that the increased ABO protein level is a causal risk factor for COVID-19 susceptibility and severity ( Hernández-Cordero et al, 2021 ). Clinical COVID-19 phenotypes, especially circulatory system complications, including thrombotic and coagulation-related phenotypes, were associated with genetically predicted increased ABO expression levels ( Pathak et al, 2020 ).…”

Section: Host Genetics Beyond Hla and Kirmentioning

confidence: 99%

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An immunogenetic view of COVID-19

et al. 2021

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Meeting the challenges brought by the COVID-19 pandemic requires an interdisciplinary approach. In this context, integrating knowledge of immune function with an understanding of how genetic variation influences the nature of immunity is a key challenge. Immunogenetics can help explain the heterogeneity of susceptibility and protection to the viral infection and disease progression. Here, we review the knowledge developed so far, discussing fundamental genes for triggering the innate and adaptive immune responses associated with a viral infection, especially with the SARS-CoV-2 mechanisms. We emphasize the role of the HLA and KIR genes, discussing what has been uncovered about their role in COVID-19 and addressing methodological challenges of studying these genes. Finally, we comment on questions that arise when studying admixed populations, highlighting the case of Brazil. We argue that the interplay between immunology and an understanding of genetic associations can provide an important contribution to our knowledge of COVID-19.

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Section: Host Genetics Beyond Hla and Kirmentioning

confidence: 90%

Section: Host Genetics Beyond Hla and Kirmentioning

confidence: 99%

An immunogenetic view of COVID-19

et al. 2021

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“…The O allele lacks this enzymatic activity due to a truncating mutation. Very recently, the ABO plasma protein levels have been associated with COVID-19 susceptibility and severity 43 . Worthy of note, with a single exception, the genome-wide association studies published so far have been all concordant in indicating significant association with the ABO locus on chromosome 9 (9q34) 18 , 19 , 38 , 43 – 45 .…”

Section: Discussionmentioning

confidence: 99%

Country-level factors dynamics and ABO/Rh blood groups contribution to COVID-19 mortality

Monaco

Pantaleo

Amoroso

et al. 2021

Sci Rep

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The identification of factors associated to COVID-19 mortality is important to design effective containment measures and safeguard at-risk categories. In the last year, several investigations have tried to ascertain key features to predict the COVID-19 mortality tolls in relation to country-specific dynamics and population structure. Most studies focused on the first wave of the COVID-19 pandemic observed in the first half of 2020. Numerous studies have reported significant associations between COVID-19 mortality and relevant variables, for instance obesity, healthcare system indicators such as hospital beds density, and bacillus Calmette-Guerin immunization. In this work, we investigated the role of ABO/Rh blood groups at three different stages of the pandemic while accounting for demographic, economic, and health system related confounding factors. Using a machine learning approach, we found that the “B+” blood group frequency is an important factor at all stages of the pandemic, confirming previous findings that blood groups are linked to COVID-19 severity and fatal outcome.

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“…The IgM downregulation leads also to downstream anti-A and anti-B isoagglutinin activity, hallmarks of innate immune activity [116] . Finally, the apparent protective effect of blood group O may be a consequence of lower ABO protein concentration, although the exact underlying mechanism has not yet been unraveled [136] .…”

Section: Associated Genetic Polymorphisms ( Table 3 )mentioning

confidence: 99%