Differential T cell reactivity to endemic coronaviruses and SARS-CoV-2 in community and health care workers

da Silva Antunes, Ricardo; Pallikkuth, Suresh; Williams, Erin; Esther, Dawen Yu; Mateus, Jose; Quiambao, Lorenzo; Wang, Eric; Rawlings, Stephen A; Stadlbauer, Daniel; Jiang, Kaijun; Amanat, Fatima; Arnold, David; Andrews, David; Fuego, Irma; Dan, Jennifer M; Grifoni, Alba; Weiskopf, Daniela; Krammer, Florian; Crotty, Shane; Hoffer, Michael E; Pahwa, Savita G; Sette, Alessandro

Herein we measured CD4 (+) T cell responses against common cold corona (CCC) viruses and SARS-CoV-2 in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC reactive T cells in SARS-CoV-2 seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T cell reactivity was decreased in SARS-CoV-2 infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.