The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity

Inna G Ovsyannikova, Iana H Haralambieva, Stephen N Crooke, Gregory A Poland, Richard B Kennedy, Inna G Ovsyannikova, Iana H Haralambieva, Stephen N Crooke, Gregory A Poland, Richard B Kennedy

Abstract

This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus-mediated disease. The initial sections focus on seasonal coronaviruses, SARS-CoV, and MERS-CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS-CoV-2 and COVID-19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS-CoV-2.

Keywords: COVID-19; GWAS; HLA; SARS; SARS-CoV-2; alleles; coronavirus; genes; genetic variation; genome-wide association study; immunogenetics; polymorphisms; severe acute respiratory syndrome; single nucleotide; systems biology; vaccine.

Conflict of interest statement

Dr Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr Poland offers consultative advice on vaccine development to Merck & Co. Inc, Avianax, Adjuvance, Valneva, Medicago, Sanofi Pasteur, GlaxoSmithKline, and Emergent Biosolutions. Drs. Poland and Ovsyannikova hold three patents related to measles and vaccinia peptide research. Dr Kennedy holds a patent on vaccinia peptide research. Dr Kennedy has received funding from Merck Research Laboratories to study waning immunity to measles and mumps after immunization with the MMR‐II® vaccine. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding from ICW Ventures for preclinical studies on a peptide‐based COVID‐19 vaccine. All other authors declare no competing financial interests. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
The impact of host genetics and viral variation on SARS‐CoV‐2 infection and COVID‐19 severity. Individuals in the population harbor single nucleotide polymorphisms (SNPs) across a variety of genes (eg, ACE2, TMPRSS2, HLA, CD147, MIF, IFNG, IL6) that have been implicated in the pathology and immunology of SARS‐CoV‐2 and other pathogenic coronaviruses. These and other genetic variants may modulate disease susceptibility, increase or decrease disease severity, alter the variety of symptoms developed, and affect the magnitude and/or quality of the immune responses against SARS‐CoV‐2. In addition to host genetic variation, genetic variants of SARS‐CoV‐2 (and other pathogenic coronaviruses) can exhibit differences in biological activity. Single amino acid mutations in the spike glycoprotein can modulate ACE2 binding or alter B cell epitopes to promote immune escape or render monoclonal antibodies ineffective, while mutations in non‐structural/accessory proteins can promote the development of resistance to antivirals, alter T cell epitopes, disrupt cell mediated immunity, and modulate host cellular interactions with viral particles

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