Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals.

Abstract

PURPOSE:

Emerging 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.

METHODS:

Exploiting 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.

RESULTS:

We 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.

CONCLUSION:

This 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/.

• Authors: Giuseppe D'Alterio, Vito Alessandro Lasorsa, Ferdinando Bonfiglio, Sueva Cantalupo, Barbara Eleni Rosato, Immacolata Andolfo, Roberta Russo, Umberto Esposito, Giulia Frisso, Pasquale Abete, Gian Marco Cassese, Giuseppe Servillo, Ivan Gentile, Carmelo Piscopo, Matteo Della Monica, Giuseppe Fiorentino, Angelo Boccia, Giovanni Paolella, Veronica Ferrucci, Pasqualino de Antonellis, Roberto Siciliano, Fathem Asadzadeh, Pellegrino Cerino, Carlo Buonerba, Biancamaria Pierri, Massimo Zollo, Achille Iolascon, Mario Capasso
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 24 Issue 8 Pg. 1653-1663 (08 2022) ISSN: 1530-0366 [Electronic] United States
• PMID: 35511137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• COLEC10 protein, human
• Collectins
• Lectins

Topics

• Aged
• COVID-19 (genetics)
• Collectins (genetics, metabolism)
• Germ Cells
• Humans
• Lectins (genetics)
• SARS-CoV-2
• Exome Sequencing