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A Virus-Specific Immune Rheostat in the Immunome of Patients Recovering From Mild COVID-19

  • Yeo, Joo Guan1, 2, 3
  • Leong, Jing Yao1
  • Tay, Shi Huan1, 3
  • Nadua, Karen Donceras3, 4, 5
  • Anderson, Danielle E.3
  • Lim, Amanda Jin Mei1
  • Ng, Xiang Wen6
  • Poh, Su Li1
  • Guo, Dianyan1
  • Yaung, Katherine Nay1, 3
  • Kumar, Pavanish1
  • Wasser, Martin1
  • Hazirah, Sharifah Nur1
  • Sutamam, Nursyuhadah1
  • Chua, Camillus Jian Hui1
  • Qui, Martin3
  • Foo, Randy3
  • Gamage, Akshamal Mihiranga3
  • Yeo, Kee Thai1, 3, 7
  • Ramakrishna, Lakshmi1
  • And 13 more
  • 1 Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore , (Singapore)
  • 2 Rheumatology and Immunology Service, Department of Pediatric Subspecialities, KK Women’s and Children’s Hospital, Singapore , (Singapore)
  • 3 Duke-NUS Medical School, Singapore , (Singapore)
  • 4 Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore , (Singapore)
  • 5 Infectious Disease Service, Department of Pediatrics, KK Women’s and Children’s Hospital, Singapore , (Singapore)
  • 6 Department of Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore , (Singapore)
  • 7 Department of Neonatology, KK Women’s and Children’s Hospital, Singapore , (Singapore)
  • 8 National Centre for Infectious Diseases, Singapore , (Singapore)
  • 9 Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore , (Singapore)
  • 10 Lee Kong Chian School of Medicine, Singapore , (Singapore)
  • 11 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Singapore , (Singapore)
Published Article
Frontiers in Immunology
Frontiers Media SA
Publication Date
May 25, 2021
DOI: 10.3389/fimmu.2021.674279
  • Immunology
  • Original Research


An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (Teff) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (Treg) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ+ memory CD4+ T cells and virus-specific follicular helper T (TFH) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.

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