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The Seven Enigmas of Sars-Cov-2: From the Past to the Future Publisher



Andreakos E ; Arkin L ; Bastard P ; Bolze A ; Borghesi A ; Brodin P ; Casanova J L ; Casari G ; Cobat A ; Drolet B ; Fellay J ; Hsieh E W Y ; Meyts I ; Mogensen T H Show All Authors
Authors
  1. Andreakos E
  2. Arkin L
  3. Bastard P
  4. Bolze A
  5. Borghesi A
  6. Brodin P
  7. Casanova J L
  8. Casari G
  9. Cobat A
  10. Drolet B
  11. Fellay J
  12. Hsieh E W Y
  13. Meyts I
  14. Mogensen T H
  15. Sancho Shimizu V
  16. Spaan A N
  17. Su H C
  18. Vinh D C
  19. Yatim A
  20. Zhang Q
  21. Zhang S Y
  22. Abel L
  23. Aiuti A
  24. Al Muhsen S
  25. Arias A A
  26. Arkin L M
  27. Feldman H B
  28. Bondarenko A
  29. Bousfiha A A
  30. Christodoulou J
  31. Colobran R
  32. Condino Neto A
  33. Constantinescu S N
  34. Drolet B A
  35. Dundar M
  36. Espinosa Padilla S
  37. Flores C
  38. Froidure A
  39. Gorochov G
  40. Hagin D
  41. Halwani R
  42. Hammarstrom L
  43. Itan Y
  44. Jouanguy E
  45. Kaja E
  46. Lau Y L
  47. Mansouri D
  48. Marodi L
  49. Ng L F P
  50. Novelli A
  51. Novelli G
  52. Okada S
  53. Okamoto K
  54. Ozcelik F
  55. Pan Hammarstrom Q
  56. De Diego R P
  57. Perlin D S
  58. Pue A
  59. Pujol A
  60. Renia L
  61. Shahrooei M
  62. Shcherbina A
  63. Slaby O
  64. Soler Palacin P
  65. Tancevski I
  66. Tangye S G
  67. Tayoun A A
  68. Thorball C
  69. Tiberghien P
  70. Turvey S E

Source: Journal of Human Immunity Published:2025


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 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. © 2025 Andreakos et al.
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