Immune Features of COVID-19 Convalescent Individuals Revealed by a Single-cell RNA Sequencing (preprint)

ABSTRACT

Background: The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, it remains unclear whether immune responses following natural infection can be sustained or potentially prove critical for long-term immune protection against SARS-CoV-2 reinfection. Here, we systematically mapped the phenotypic landscape of SARS-CoV-2-specific immune responses in peripheral blood samples of 4 healthy donors and 13 convalescent patients with COVID-19, including moderate and severe cases, by single-cell RNA sequencing. Results: The relative percentage of the CD8+ effector memory subset was increased in both convalescent moderate and severe cases, but NKT-CD160 and maginal zone B clusters were decreased. Innate immune responses were attenuated reflected by decreased expression of genes involved in interferon-gamma, leukocyte migration and neutrophil mediated immune response in convalescent COVID-19 patients. Functions of T cell were strengthened in convalescent COVID-19 patients by clear endorsement of increased expression of genes involved in biological processes of regulation of T cell activation, differentiation and cell-cell adhesion. In addition, T cell mediated immune responses were enhanced with remarkable clonal expansions of TCR and increased transition of CD4+ effector memory and CD8+ effector-GNLY in severe subjects. B cell immune responses displayed sophisticated and dual functions during convalescence of COVID-19, providing a novel mechanism that B cell activation was observed especially in moderate while humoral immune response was weakened. Interestingly, HLA class I genes displayed downregulation while HLA class II genes upregulation in both T and B cell subsets in convalescent individuals. Notably, some unique IGV genes in severe patients may facilitate the design of vaccines. Conclusions: Our collective dataset showed that innate immunity was declined but SARS-CoV-2-specific T cell responses were retained even strengthened whereas sophisticated and dual functions of B cells, including declined humoral immunity were presented at several months following infections, which provided insights into evaluation of possibility of reinfection of exposed individuals with COVID-19 and facilitation to design of effective therapeutics and vaccines.