The seven enigmas of SARS-CoV-2: From the past to the future

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 (IEI) and their phenocopies. We deciphered the pathogenesis of critical COVID-19 pneumonia and multisystemic inflammatory syndrome in children (MIS-C) in ~15% and 2% of cases, respectively, thereby revealing general mechanisms of severe disease. We also defined neuro-COVID-19 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 post 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.

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Publication Details

Journal
Journal of Human Immunity
Published
2025-09-24
DOI
https://doi.org/10.70962/jhi.20250149
Citations
2
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
2.79
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article

The seven enigmas of SARS-CoV-2: From the past to the future

Pere Soler‐Palacín, David S. Perlin, Evangelos Andreakos, Lennart Hammarström et al.
2 citations
Journal of Human Immunity
SARS-CoV-2 and COVID-19 Research
2.79
article

The seven enigmas of SARS-CoV-2: From the past to the future

Pere Soler‐Palacín, David S. Perlin, Evangelos Andreakos, Lennart Hammarström, Andrés A. Arias, Paul Bastard, Rebeca Pérez de Diego, Antonio Novelli, Lisa F. P. Ng, Helen C. Su, László Maródi, Elena W.Y. Hsieh, Lisa M. Arkin, Vanessa Sancho‐Shimizu, Pierre Tiberghien, Satoshi Okada, Ahmad Yatim, Aurélie Cobat, Hagit Baris Feldman, Stefan N. Constantinescu, Antoine Froidure, Isabelle Meyts, Stuart E. Turvey, Rabih Halwani, Sara Elva Espinosa‐Padilla, Elżbieta Kaja, Ivan Tancevski, Alexandre Bolze, John Christodoulou, Qian Zhang, Jean‐Laurent Casanova, Munis Dündar, David Hagin, Guy Gorochov, Ahmad Abou Tayoun, Ahmed Aziz Bousfiha, Alessandro Aiuti, Trine Hyrup Mogensen, András N. Spaan, Roger Colobrán, Qiang Pan‐Hammarström, Anne Puel, Emmanuelle Jouanguy, Beth A. Drolet, Fırat Özçelik, Shen‐Ying Zhang, Laurent Rénia, Christian Wandall Thorball, Petter Brodin, Davood Mansouri, Alessandro Borghesi, Giorgio Casari, Aurora Pujol, Mohammad Shahrooei, Giuseppe Novelli, Jacques Fellay, Donald C. Vinh, Laurent Abel, Anna Shcherbina, Stuart G. Tangye, Yu-Lung Lau, Yuval Itan, Antonio Condino-Neto, Carlos Flores, Saleh Al‐Muhsen, Keisuke Okamoto, Anastasiia Bondarenko, Ondřej Slabý
article en
2 citations

Abstract

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 (IEI) and their phenocopies. We deciphered the pathogenesis of critical COVID-19 pneumonia and multisystemic inflammatory syndrome in children (MIS-C) in ~15% and 2% of cases, respectively, thereby revealing general mechanisms of severe disease. We also defined neuro-COVID-19 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 post 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.

Journal of Human ImmunityVol. 1(4)
University of Geneva (CH), Howard Hughes Medical Institute (US), University of Wisconsin–Madison (US), Vita-Salute San Raffaele University (IT), Inserm (FR), Utrecht University (NL), Aarhus University (DK), Université Paris Cité (FR), Academy of Athens (GR), Hospital for Sick Children (CA), Hammersmith Hospital (GB), McGill University Health Centre (CA), Aarhus University Hospital (DK), Karolinska Institutet (SE), University Medical Center Utrecht (NL), Sorbonne Université (FR), Institut Necker Enfants Malades (FR), Hospital for Sick Children Pediatric Center (US), University Hospital Foundation (CA), Assistance Publique – Hôpitaux de Paris (FR), University Hospital of Geneva (CH), NIHR Imperial Biomedical Research Centre (GB), Mother Hospital (IN), National Institute of Allergy and Infectious Diseases (US), Institute of Child Health (IN), Wisconsin Division of Public Health (US), Helix (United States) (US), Institute of Infection and Immunity (CA), Institut des Maladies Génétiques Imagine (FR), Imperial College London (GB), École Polytechnique Fédérale de Lausanne (CH), Royal College of Paediatrics and Child Health (GB), Geneva College (US), Rockefeller University (US), University of Colorado Denver (US), University of Lausanne (CH), KU Leuven (BE)
Openalex Percentile: Top 8%
SARS-CoV-2 and COVID-19 Research
2.79
DOIOpen Access PDFOpenAlex
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