ArticleGenetics in medicine : official journal of the American College of Medical Genetics2022
Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 11 citations in OpenAlex.
- Temporal Proteomic Profiling of Hospitalized COVID-19 Patients Reveals Prognostic Biomarkers.Journal of proteome research · 2026Article
- The role of complement in long COVID pathogenesis.JCI insight · 2025Review
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- Targeting ATP2B1 impairs PI3K/Akt/FOXO signaling and reduces SARS-COV-2 infection and replication.EMBO reports · 2024Article
- Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.Immunobiology · 2023Review
- A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G.Frontiers in immunology · 2023Review
- DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation.Frontiers in neurology · 2023Article
- COVID-19 severity: does the genetic landscape of rare variants matter?Frontiers in genetics · 2023Article
- Exome-Wide Association Study Reveals Host Genetic Variants Likely Associated with the Severity of COVID-19 in Patients of European Ancestry.Life (Basel, Switzerland) · 2022Article
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Authors and funding
28 authors at 7 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeEmerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease.
methodsExploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19.
resultsWe found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue.
conclusionThis study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/.
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