Review

. 2022 Feb;23(2):159-164.

doi: 10.1038/s41590-021-01030-z. Epub 2021 Oct 18.

A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

Evangelos Andreakos¹, Laurent Abel^{2

3

4}, Donald C Vinh^{5

6}, Elżbieta Kaja⁷, Beth A Drolet⁸, Qian Zhang^{2

3

4}, Cliona O'Farrelly⁹, Giuseppe Novelli¹⁰, Carlos Rodríguez-Gallego^{11

12}, Filomeen Haerynck¹³, Carolina Prando¹⁴, Aurora Pujol^{15

16

17}; COVID Human Genetic Effort; Helen C Su¹⁸, Jean-Laurent Casanova^{2

3

4

19}, András N Spaan^{20

21}

Collaborators, Affiliations

Collaborators

COVID Human Genetic Effort:
Paul Bastard, Catherine M Biggs, Benedetta Bigio, Bertrand Boisson, Alexandre Bolze, Anastasiia Bondarenko, Petter Brodin, Samya Chakravorty, John Christodoulou, Aurelié Cobat, Antonio Condino-Neto, Stefan N Constantinescu, Hagit Baris Feldman, Jacques Fellay, Carlos Flores, Rabih Halwani, Emmanuelle Jouanguy, Yu-Lung Lau, Isabelle Meyts, Trine H Mogensen, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Rebeca Pérez de Diego, Anna M Planas, Anne Puel, Lluis Quintana-Murci, Laurent Renia, Igor Resnick, Anna Sediva, Anna Shcherbina, Ondrej Slaby, Ivan Tancevski, Stuart E Turvey, K M Furkan Uddin, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Shen-Ying Zhang

Affiliations

¹ Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. vandreakos@bioacademy.gr.
² St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
³ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
⁴ University of Paris, Imagine Institute, Paris, France.
⁵ Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montréal, Québec, Canada.
⁶ Infectious Disease Susceptibility Program, Research Institute, McGill University Health Centre, Montréal, Québec, Canada.
⁷ MNM Diagnostics Inc., Lewes, DE, USA.
⁸ Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
⁹ Comparative Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
¹⁰ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
¹¹ Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Las Palmas, Spain.
¹² Department of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Las Palmas, Spain.
¹³ Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
¹⁴ Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil.
¹⁵ Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁶ Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain.
¹⁷ Center for Biomedical Research on Rare Diseases U759 (CIBERER), ISCIII, Barcelona, Spain.
¹⁸ Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁹ Howard Hughes Medical Institute, New York, NY, USA.
²⁰ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. aspaan@rockefeller.edu.
²¹ Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. aspaan@rockefeller.edu.

PMID: 34667308
PMCID: PMC8524403
DOI: 10.1038/s41590-021-01030-z

Review

A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

Evangelos Andreakos et al. Nat Immunol. 2022 Feb.

. 2022 Feb;23(2):159-164.

doi: 10.1038/s41590-021-01030-z. Epub 2021 Oct 18.

Authors

Collaborators

COVID Human Genetic Effort:
Paul Bastard, Catherine M Biggs, Benedetta Bigio, Bertrand Boisson, Alexandre Bolze, Anastasiia Bondarenko, Petter Brodin, Samya Chakravorty, John Christodoulou, Aurelié Cobat, Antonio Condino-Neto, Stefan N Constantinescu, Hagit Baris Feldman, Jacques Fellay, Carlos Flores, Rabih Halwani, Emmanuelle Jouanguy, Yu-Lung Lau, Isabelle Meyts, Trine H Mogensen, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Rebeca Pérez de Diego, Anna M Planas, Anne Puel, Lluis Quintana-Murci, Laurent Renia, Igor Resnick, Anna Sediva, Anna Shcherbina, Ondrej Slaby, Ivan Tancevski, Stuart E Turvey, K M Furkan Uddin, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Shen-Ying Zhang

Affiliations

¹ Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. vandreakos@bioacademy.gr.
² St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
³ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
⁴ University of Paris, Imagine Institute, Paris, France.
⁵ Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montréal, Québec, Canada.
⁶ Infectious Disease Susceptibility Program, Research Institute, McGill University Health Centre, Montréal, Québec, Canada.
⁷ MNM Diagnostics Inc., Lewes, DE, USA.
⁸ Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
⁹ Comparative Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
¹⁰ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
¹¹ Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Las Palmas, Spain.
¹² Department of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Las Palmas, Spain.
¹³ Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
¹⁴ Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil.
¹⁵ Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁶ Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain.
¹⁷ Center for Biomedical Research on Rare Diseases U759 (CIBERER), ISCIII, Barcelona, Spain.
¹⁸ Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁹ Howard Hughes Medical Institute, New York, NY, USA.
²⁰ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. aspaan@rockefeller.edu.
²¹ Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. aspaan@rockefeller.edu.

PMID: 34667308
PMCID: PMC8524403
DOI: 10.1038/s41590-021-01030-z

Erratum in

Author Correction: A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection.
Andreakos E, Abel L, Vinh DC, Kaja E, Drolet BA, Zhang Q, O'Farrelly C, Novelli G, Rodríguez-Gallego C, Haerynck F, Prando C, Pujol A; COVID Human Genetic Effort; Su HC, Casanova JL, Spaan AN. Andreakos E, et al. Nat Immunol. 2022 Feb;23(2):341. doi: 10.1038/s41590-021-01096-9. Nat Immunol. 2022. PMID: 34819675 Free PMC article. No abstract available.

Abstract

SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection.**
Inclusion criteria, and approach for the identification and validation of inborn variants conferring resistance to SARS-CoV-2 infection (http://www.covidhge.com). Created with BioRender.com.

See this image and copyright information in PMC

Comment in

The search for people who never get COVID.
Mallapaty S. Mallapaty S. Nature. 2021 Nov;599(7884):191. doi: 10.1038/d41586-021-02978-6. Nature. 2021. PMID: 34716433 No abstract available.

References

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1. Quintana-Murci L. Human immunology through the lens of evolutionary genetics. Cell. 2019;177:184–199. doi: 10.1016/j.cell.2019.02.033. - DOI - PubMed
1. Casanova JL, Abel L. Inborn errors of immunity to infection: the rule rather than the exception. J. Exp. Med. 2005;202:197–201. doi: 10.1084/jem.20050854. - DOI - PMC - PubMed
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A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

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A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

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Erratum in

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Conflict of interest statement

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