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Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals.
D'Alterio, Giuseppe; Lasorsa, Vito Alessandro; Bonfiglio, Ferdinando; Cantalupo, Sueva; Rosato, Barbara Eleni; Andolfo, Immacolata; Russo, Roberta; Esposito, Umberto; Frisso, Giulia; Abete, Pasquale; Cassese, Gian Marco; Servillo, Giuseppe; Gentile, Ivan; Piscopo, Carmelo; Della Monica, Matteo; Fiorentino, Giuseppe; Boccia, Angelo; Paolella, Giovanni; Ferrucci, Veronica; de Antonellis, Pasqualino; Siciliano, Roberto; Asadzadeh, Fathem; Cerino, Pellegrino; Buonerba, Carlo; Pierri, Biancamaria; Zollo, Massimo; Iolascon, Achille; Capasso, Mario.
  • D'Alterio G; European School of Molecular Medicine, Università degli Studi di Milano, Milan, Italy; CEINGE Biotecnologie Avanzate, Naples, Italy.
  • Lasorsa VA; CEINGE Biotecnologie Avanzate, Naples, Italy.
  • Bonfiglio F; Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Naples, Italy.
  • Cantalupo S; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Rosato BE; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Andolfo I; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Russo R; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Esposito U; CEINGE Biotecnologie Avanzate, Naples, Italy.
  • Frisso G; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Abete P; COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, Naples, Italy.
  • Cassese GM; COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, Naples, Italy.
  • Servillo G; Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy.
  • Gentile I; Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
  • Piscopo C; Medical and Laboratory Genetics Unit, A.O.R.N. Antonio Cardarelli, Naples, Italy.
  • Della Monica M; Medical and Laboratory Genetics Unit, A.O.R.N. Antonio Cardarelli, Naples, Italy.
  • Fiorentino G; Cotugno Hospital, Azienda Ospedaliera di Rilievo Nazionale Ospedali dei Colli, Naples, Italy.
  • Boccia A; CEINGE Biotecnologie Avanzate, Naples, Italy.
  • Paolella G; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Ferrucci V; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • de Antonellis P; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Siciliano R; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Asadzadeh F; European School of Molecular Medicine, Università degli Studi di Milano, Milan, Italy; CEINGE Biotecnologie Avanzate, Naples, Italy.
  • Cerino P; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Napoli, Italy.
  • Buonerba C; Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana," University of Salerno, Baronissi, Italy.
  • Pierri B; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Napoli, Italy; Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana," University of Salerno, Baronissi, Italy.
  • Zollo M; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Iolascon A; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • Capasso M; CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy. Electronic address: mario.capasso@unina.it.
Genet Med ; 24(8): 1653-1663, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1819495
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/.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Topics: Variants Limits: Aged / Humans Language: English Journal: Genet Med Journal subject: Genetics, Medical Year: 2022 Document Type: Article Affiliation country: J.gim.2022.04.007

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Topics: Variants Limits: Aged / Humans Language: English Journal: Genet Med Journal subject: Genetics, Medical Year: 2022 Document Type: Article Affiliation country: J.gim.2022.04.007