A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection
Evangelos Andreakos, Laurent Abel, Donald C. Vinh, Elżbieta Kaja, Beth A. Drolet, Qian Zhang, Cliona O’Farrelly, Giuseppe Novelli, Carlos Rodríguez‐Gallego, Filomeen Haerynck, Carolina Prando, Aurora Pujol, COVID Human Genetic Effort, Paul Bastard, Catherine M. Biggs, Benedetta Bigio, Bertrand Boisson, Alexandre Bolze, Анастасія Бондаренко, Petter Brodin, Samya Chakravorty, John Christodoulou, Aurélie Cobat, Antônio Condino‐Neto, Stefan N. Constantinescu, Hagit Baris Feldman, Jacques Fellay, Carlos Flores, Rabih Halwani, Emmanuelle Jouanguy, YL Lau, Isabelle Meyts, Trine H. Mogensen, Satoshi Okada, Keisuke Okamoto, Tayfun Özçelık, Qiang Pan‐Hammarström, Rebeca Pérez de Diego, Anna M. Planas, Anne Puel, Lluís Quintana‐Murci, Laurent Rénia, Igor Resnick, Anna Šedivá, Anna Shcherbina, Ondřej Slabý, Ivan Tancevski, Stuart E. Turvey, K. M. Furkan Uddin, Diederik van de Beek, Mayana Zatz, Paweł Zawadzki, Shen‐Ying Zhang, Helen C. Su, Jean‐Laurent Casanova, András N. Spaan
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.