Systems and Longitudinal Analysis Reveals Early-Stage and Highly Coordinated Immune Responses in Mild COVID-19 Patients

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 reveals the first full picture and early-stage trajectory of highly-coordinated immune responses in mild COVID-19 patients. Funding: The Predi-COVID study is supported by the Luxembourg National Research Fund (FNR) (Predi-COVID, 14716273) and the Andre Losch Fondation. We also highly appreciate the expert support of the IBBL processing and biorepository teams. F.Q.H. was partially supported by FNR CORE programme grant (CORE/14/BM/8231540/GeDES), FNR AFR- RIKEN bilateral programme (TregBAR, 11228353, F.Q.H. and M.O.) and PRIDE programme grants (PRIDE/11012546/NEXTIMMUNE and PRIDE/10907093/CRITICS). C.H. was partially supported by the FNR fast-track call COVID-19/2020-1/14703957/COV-Immun. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: All collections were performed with approval from relevant ethic organizations. Informed consent was obtained from each participant prior to collection. The blood sampling was performed by nurses from Clinical and Epidemiological Investigation Centre (CIEC) of LIH.