Host Genetic Loci LZTFL1 and CCL2 Associated with SARS-CoV-2 Infection and Severity of COVID-19

Overview

Journal Int J Infect Dis

Publisher Elsevier

Specialty Infectious Diseases

Date 2022 Jun 26

PMID 35753602

Authors

Jule Ruter

Srinivas Reddy Pallerla

Christian G Meyer

Nicolas Casadei

Michael Sonnabend

Silke Peter

Dennis Nurjadi

Le Thi Kieu Linh

Rolf Fendel

Siri Gopel

Olaf Riess

Peter G Kremsner

Thirumalaisamy P Velavan

Affiliations

Soon will be listed here.

Abstract

Objectives: Host genetic factors contribute to the variable severity of COVID-19. We examined genetic variants from genome-wide association studies and candidate gene association studies in a cohort of patients with COVID-19 and investigated the role of early SARS-CoV-2 strains in COVID-19 severity.

Methods: This case-control study included 123 COVID-19 cases (hospitalized or ambulatory) and healthy controls from the state of Baden-Wuerttemberg, Germany. We genotyped 30 single nucleotide polymorphisms, using a custom-designed panel. Cases were also compared with the 1000 genomes project. Polygenic risk scores were constructed. SARS-CoV-2 genomes from 26 patients with COVID-19 were sequenced and compared between ambulatory and hospitalized cases, and phylogeny was reconstructed.

Results: Eight variants reached nominal significance and two were significantly associated with at least one of the phenotypes "susceptibility to infection", "hospitalization", or "severity": rs73064425 in LZTFL1 (hospitalization and severity, P <0.001) and rs1024611 near CCL2 (susceptibility, including 1000 genomes project, P = 0.001). The polygenic risk score could predict hospitalization. Most (23/26, 89%) of the SARS-CoV-2 genomes were classified as B.1 lineage. No associations of SARS-CoV-2 mutations or lineages with severity were observed.

Conclusion: These host genetic markers provide insights into pathogenesis and enable risk classification. Variants which reached nominal significance should be included in larger studies.

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