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

Yeo, Joo Guan; Leong, Jing Yao; Tay, Shi Huan; Nadua, Karen Donceras; Anderson, Danielle E.; Lim, Amanda Jin Mei; Ng, Xiang Wen; Poh, Su Li; Guo, Dianyan; Yaung, Katherine Nay; Kumar, Pavanish; Wasser, Martin; Hazirah, Sharifah Nur; Sutamam, Nursyuhadah; Chua, Camillus Jian Hui; Qui, Martin; Foo, Randy; Gamage, Akshamal Mihiranga; Yeo, Kee Thai; Ramakrishna, Lakshmi; Arkachaisri, Thaschawee; Young, Barnaby E.; Lye, David Chien; Wang, Lin-Fa; Chong, Chia Yin; Tan, Natalie Woon Hui; Li, Jiahui; Kam, Kai-Qian; Ginhoux, Florent; Thoon, Koh Cheng; Chan, Jerry Kok Yen; Yung, Chee Fu; Albani, Salvatore

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 (T(eff)) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (T(reg)) 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 (T(FH)) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.