Deep immune profiling reveals early-stage and highly coordinated immune responses in mild COVID-19 patients

Capelle, C. M.; Cire, S.; Domingues, O.; Ernens, I.; Hedin, F.; Fischer, A.; Snoeck, C.; Ammerlaan, W.; Konstantinou, M.; Grzyb, K.; Skupin, A.; Carty, C. L.; Hilger, C.; Gilson, G.; Celebic, A.; Del Sol, A.; Kaplan, I. M.; Betsou, F.; Abdelrahman, T.; Cosma, A.; Vaillant, M. T.; Fagherazzi, G.; Ollert, M.; Hefeng, F. Q.

While immunopathology has been widely studied in severe COVID-19 patients, immunoprotective factors in non-hospitalized patients have remained largely elusive. We systematically analyzed 484 peripheral immune cell signatures, various serological parameters and TCR repertoire in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 control individuals. Within three days following PCR diagnosis, we observed coordinated responses of CD4 and CD8 T cells, various antigen presenting cells and antibody-secreting cells in mild, but not hospitalized COVID-19 patients. This early-stage SARS-CoV-2-specific response was predominantly characterized by substantially expanded clonotypes of CD4 and less of CD8 T cells. The early-stage responses of T cells and dendritic cells were highly predictive for later seroconversion and protective antibody levels after three weeks in mild non-hospitalized, but not in hospitalized patients. Our systemic analysis provides the first full picture and early-stage trajectory of highly coordinated immune responses in mild COVID-19 patients.