Integrated longitudinal immunophenotypic, transcriptional, and repertoire analyses delineate immune responses in patients with COVID-19

Abstract

To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+ T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+ T lymphocytes, while CD4+ T cells were less expanded and skewed toward TCM and TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+ GZMB+ effector cells were clonally expanded both during the infection and post-infection, while CD8+ GZMK+ lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+ GZMB+ and GZMK+ subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+ T cell population with memory precursor-like features.

Anti-spike antibodies and neutralising antibody activity in people living with HIV vaccinated with COVID-19 mRNA-1273 vaccine: a prospective single-centre cohort study

“…HEK 293TN hACE2 cells were derived from HEK 293TN after transduction with a lentiviral vector coding for human ACE2 gene and Hygromycin resistance as previously described. 13 …”

Analysis of TCR Repertoire by High-Throughput Sequencing Indicates the Feature of T Cell Immune Response after SARS-CoV-2 Infection

“…Moreover, a higher proportion of SARS-CoV-2 specific CD8 + T cells were detected in mild cases, and these CD8 + T cells have extensive and strong memory after the recovery period of COVID-19 [ 14 ]. On the contrary, a significant reduction in effector memory CD4 + T cells, which were less expanded and skewed toward central memory T cells and TH2-like phenotypes, was detected in COVID-19 patients with severe disease, whereas terminally differentiated CD8 + GZMK + effector cells were clonally expanded both during and after the infection [ 15 ]. The CD4 + T memory response was detected in all recovered patients from COVID-19, and 70% of patients had established CD8 + T memory response to SARS-CoV-2, lasting for more than 2 months [ 16 , 17 ].…”

Asymptomatic COVID-19 Individuals Tend to Establish Relatively Balanced Innate and Adaptive Immune Responses

“…As we know, individual immune responses potentially orchestrate the pathology and play important roles in determining different clinical courses of SARS-CoV-2 infection. A recent study showed an extensive and durable remodeling of immune cells during and after SARS-CoV-2 infection [11]. However, the immune mechanisms that are associated with asymptomatic infection are still largely elusive.…”

“…Different clusters had different transcriptional characteristics and functional phenotypes. The proportion of different subpopulations was closely related with severity of COVID-19 [11]. In the future, to accurately reflect the characteristics of immune phenotype of asymptomatic and symptomatic cases, it is necessary to analyze NK and monocyte clusters.…”