TY - JOUR
T1 - The seven enigmas of SARS-CoV-2
T2 - From the past to the future
AU - COVID Human Genetic Effort
AU - Andreakos, Evangelos
AU - Arkin, Lisa
AU - Bastard, Paul
AU - Bolze, Alexandre
AU - Borghesi, Alessandro
AU - Brodin, Petter
AU - Casanova, Jean Laurent
AU - Casari, Giorgio
AU - Cobat, Aurelie
AU - Drolet, Beth
AU - Fellay, Jacques
AU - Hsieh, Elena W.Y.
AU - Meyts, Isabelle
AU - Mogensen, Trine H.
AU - Sancho-Shimizu, Vanessa
AU - Spaan, Andras N.
AU - Su, Helen C.
AU - Vinh, Donald C.
AU - Yatim, Ahmad
AU - Zhang, Qian
AU - Zhang, Shen Ying
AU - Abel, Laurent
AU - Aiuti, Alessandro
AU - Al-Muhsen, Saleh
AU - Arias, Andrés A.
AU - Arkin, Lisa M.
AU - Feldman, Hagit Baris
AU - Bolze, Alexandre
AU - Bondarenko, Anastasiia
AU - Bousfiha, Ahmed A.
AU - Brodin, Petter
AU - Casari, Giorgio
AU - Christodoulou, John
AU - Cobat, Aurélie
AU - Colobran, Roger
AU - Condino-Neto, Antonio
AU - Constantinescu, Stefan N.
AU - Drolet, Beth A.
AU - Dündar, Munis
AU - Espinosa-Padilla, Sara
AU - Fellay, Jacques
AU - Flores, Carlos
AU - Froidure, Antoine
AU - Gorochov, Guy
AU - Hagin, David
AU - Halwani, Rabih
AU - Hammarström, Lennart
AU - Hsieh, Elena W.Y.
AU - Itan, Yuval
AU - Perlin, David S.
N1 - Publisher Copyright:
© 2025 Andreakos et al.
PY - 2025/11/3
Y1 - 2025/11/3
N2 - Five years ago, we launched the COVID Human Genetic Effort. Our goal was to explain the clinical variability among SARS-CoV-2-exposed individuals by searching for monogenic inborn errors of immunity and their phenocopies. We deciphered the pathogenesis of critical COVID-19 pneumonia and multisystem inflammatory syndrome in children in ∼15% and 2% of cases, respectively, thereby revealing general mechanisms of severe disease. We also defined neuro-COVID genetically and immunologically in one child, while we delineated the immunological mechanisms of COVID-toes in healthy children and young adults, paving the way for their genetic study. Understanding the human genetic and immunological basis of resistance to SARS-CoV-2 infection, long COVID, and myocarditis after mRNA vaccination has been challenging, and investigations remain ongoing. This work highlights the power of patient-based basic research and large-scale international collaborative efforts to discover human genetic and immunological drivers of infectious disease phenotypes, with implications for the timely development of new medical strategies before the next pandemic arrives.
AB - Five years ago, we launched the COVID Human Genetic Effort. Our goal was to explain the clinical variability among SARS-CoV-2-exposed individuals by searching for monogenic inborn errors of immunity and their phenocopies. We deciphered the pathogenesis of critical COVID-19 pneumonia and multisystem inflammatory syndrome in children in ∼15% and 2% of cases, respectively, thereby revealing general mechanisms of severe disease. We also defined neuro-COVID genetically and immunologically in one child, while we delineated the immunological mechanisms of COVID-toes in healthy children and young adults, paving the way for their genetic study. Understanding the human genetic and immunological basis of resistance to SARS-CoV-2 infection, long COVID, and myocarditis after mRNA vaccination has been challenging, and investigations remain ongoing. This work highlights the power of patient-based basic research and large-scale international collaborative efforts to discover human genetic and immunological drivers of infectious disease phenotypes, with implications for the timely development of new medical strategies before the next pandemic arrives.
UR - https://www.scopus.com/pages/publications/105040761949
U2 - 10.70962/jhi.20250149
DO - 10.70962/jhi.20250149
M3 - Article
AN - SCOPUS:105040761949
SN - 3065-8993
VL - 1
JO - Journal of Human Immunity
JF - Journal of Human Immunity
IS - 4
M1 - e20250149
ER -
SDG 3 Good Health and Well-being