Host Genetics at the Intersection of Autoimmunity and COVID-19: A Potential Key for Heterogeneous COVID-19 Severity

COVID-19 presentation is very heterogeneous across cases, and host factors are at the forefront for the variables affecting the disease manifestation. The immune system has emerged as a key determinant in shaping the outcome of SARS-CoV-2 infection. It is mainly the deleterious unconstrained immune...

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Published in:Frontiers in immunology Vol. 11; p. 586111
Main Authors: Karaderi, Tugce, Bareke, Halin, Kunter, Imge, Seytanoglu, Adil, Cagnan, Ilgin, Balci, Deniz, Barin, Burc, Hocaoglu, Mevhibe B, Rahmioglu, Nilufer, Asilmaz, Esra, Taneri, Bahar
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Language:English
Published: Switzerland Frontiers Media S.A 22-12-2020
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Abstract COVID-19 presentation is very heterogeneous across cases, and host factors are at the forefront for the variables affecting the disease manifestation. The immune system has emerged as a key determinant in shaping the outcome of SARS-CoV-2 infection. It is mainly the deleterious unconstrained immune response, rather than the virus itself, which leads to severe cases of COVID-19 and the associated mortality. Genetic susceptibility to dysregulated immune response is highly likely to be among the host factors for adverse disease outcome. Given that such genetic susceptibility has also been observed in autoimmune diseases (ADs), a number of critical questions remain unanswered; whether individuals with ADs have a significantly different risk for COVID-19-related complications compared to the general population, and whether studies on the genetics of ADs can shed some light on the host factors in COVID-19. In this perspective, we discuss the host genetic factors, which have been under investigation in association with COVID-19 severity. We touch upon the intricate link between autoimmunity and COVID-19 pathophysiology. We put forth a number of autoimmune susceptibility genes, which have the potential to be additional host genetic factors for modifying the severity of COVID-19 presentation. In summary, host genetics at the intersection of ADs and COVID-19 may serve as a source for understanding the heterogeneity of COVID-19 severity, and hence, potentially holds a key in achieving effective strategies in risk group identification, as well as effective treatments.
AbstractList COVID-19 presentation is very heterogeneous across cases, and host factors are at the forefront for the variables affecting the disease manifestation. The immune system has emerged as a key determinant in shaping the outcome of SARS-CoV-2 infection. It is mainly the deleterious unconstrained immune response, rather than the virus itself, which leads to severe cases of COVID-19 and the associated mortality. Genetic susceptibility to dysregulated immune response is highly likely to be among the host factors for adverse disease outcome. Given that such genetic susceptibility has also been observed in autoimmune diseases (ADs), a number of critical questions remain unanswered; whether individuals with ADs have a significantly different risk for COVID-19–related complications compared to the general population, and whether studies on the genetics of ADs can shed some light on the host factors in COVID-19. In this perspective, we discuss the host genetic factors, which have been under investigation in association with COVID-19 severity. We touch upon the intricate link between autoimmunity and COVID-19 pathophysiology. We put forth a number of autoimmune susceptibility genes, which have the potential to be additional host genetic factors for modifying the severity of COVID-19 presentation. In summary, host genetics at the intersection of ADs and COVID-19 may serve as a source for understanding the heterogeneity of COVID-19 severity, and hence, potentially holds a key in achieving effective strategies in risk group identification, as well as effective treatments.
Author Rahmioglu, Nilufer
Bareke, Halin
Cagnan, Ilgin
Asilmaz, Esra
Barin, Burc
Hocaoglu, Mevhibe B
Karaderi, Tugce
Taneri, Bahar
Seytanoglu, Adil
Kunter, Imge
Balci, Deniz
AuthorAffiliation 1 Center for Health Data Science, Faculty of Medical and Health Sciences, University of Copenhagen , Copenhagen , Denmark
5 Faculty of Pharmacy, Eastern Mediterranean University , Famagusta , Cyprus
4 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Institute of Health Sciences, Marmara University , Istanbul , Turkey
9 Wellcome Centre for Human Genetics, University of Oxford , Oxford , United Kingdom
10 Nuffield Department of Women’s and Reproductive Health, University of Oxford , Oxford , United Kingdom
7 Cicely Saunders Institute of Palliative Care, Policy & Rehabilitation, Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care, King’s College London , London , United Kingdom
8 Dr Fazil Kucuk Faculty of Medicine, Eastern Mediterranean University , Famagusta , Cyprus
2 Disease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Medical and Health Sciences, University of Copenhagen , Copenhagen , Denmark
6 Vaccines and Infectio
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– name: 3 Department of Biological Sciences, Faculty of Arts and Sciences, Eastern Mediterranean University , Famagusta , Cyprus
– name: 12 Department of Genetics and Cell Biology, Faculty of Health, Medicine & Life Sciences, Institute for Public Health Genomics, Maastricht University , Maastricht , Netherlands
– name: 8 Dr Fazil Kucuk Faculty of Medicine, Eastern Mediterranean University , Famagusta , Cyprus
– name: 5 Faculty of Pharmacy, Eastern Mediterranean University , Famagusta , Cyprus
– name: 6 Vaccines and Infectious Diseases Therapeutic Research Area, The Emmes Company , Rockville, MD , United States
– name: 9 Wellcome Centre for Human Genetics, University of Oxford , Oxford , United Kingdom
– name: 7 Cicely Saunders Institute of Palliative Care, Policy & Rehabilitation, Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care, King’s College London , London , United Kingdom
– name: 11 Department of Gastroenterology, Homerton University Hospital , Clapton , United Kingdom
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  organization: Department of Genetics and Cell Biology, Faculty of Health, Medicine & Life Sciences, Institute for Public Health Genomics, Maastricht University, Maastricht, Netherlands
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ContentType Journal Article
Copyright Copyright © 2020 Karaderi, Bareke, Kunter, Seytanoglu, Cagnan, Balci, Barin, Hocaoglu, Rahmioglu, Asilmaz and Taneri.
Copyright © 2020 Karaderi, Bareke, Kunter, Seytanoglu, Cagnan, Balci, Barin, Hocaoglu, Rahmioglu, Asilmaz and Taneri 2020 Karaderi, Bareke, Kunter, Seytanoglu, Cagnan, Balci, Barin, Hocaoglu, Rahmioglu, Asilmaz and Taneri
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Keywords COVID-19
cytokine
SARS-CoV-2
susceptibility
autoimmunity
immune response
host genetics
polymorphism
Language English
License Copyright © 2020 Karaderi, Bareke, Kunter, Seytanoglu, Cagnan, Balci, Barin, Hocaoglu, Rahmioglu, Asilmaz and Taneri.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Reviewed by: Danilo Malandrino, University of Florence, Italy; Kuender D. Yang, Mackay Memorial Hospital, Taiwan
These authors have contributed equally to this work
Edited by: Pier Luigi Meroni, Istituto Auxologico Italiano (IRCCS), Italy
This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology
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Snippet COVID-19 presentation is very heterogeneous across cases, and host factors are at the forefront for the variables affecting the disease manifestation. The...
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SubjectTerms Autoimmune Diseases - genetics
autoimmunity
Autoimmunity - genetics
COVID-19
COVID-19 - genetics
Genetic Predisposition to Disease
host genetics
Humans
immune response
Immunology
SARS-CoV-2
Severity of Illness Index
susceptibility
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Title Host Genetics at the Intersection of Autoimmunity and COVID-19: A Potential Key for Heterogeneous COVID-19 Severity
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