High levels of endemic coronaviruses reactive CD4+ T cells in SARS-CoV-2 seronegative health care workers

Healthcare workers (HCW) due to occupational exposure to patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a population at risk during the current coronavirus disease-2019 (COVID-19) pandemic. Pre-existing immunity induced by the exposition to several pathogens, including respiratory viruses, can shape susceptibility to infections but little is known about the presence of cross-reactive memory T cells that have the potential to recognize SARS-CoV-2. 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 reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses shown to be consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC reactivity was consistently 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.