One-Year Sustained Cellular and Humoral Immunities in Coronavirus Disease 2019 (COVID-19) Convalescents.

BACKGROUND: The longitudinal antigen-specific immunity in COVID-19 convalescents is crucial for long-term protection upon individual re-exposure to SARS-CoV-2, and even more pivotal for ultimately achieving population-level immunity. We conducted this cohort study to better understand the features of immune memory in individuals with different disease severities at 1 year post-disease onset. METHODS: We conducted a systematic antigen-specific immune evaluation in 101 COVID-19 convalescents, who had asymptomatic, mild, moderate, or severe disease, through 2 visits at months 6 and 12 after disease onset. The SARS-CoV-2-specific antibodies, comprising neutralizing antibody (NAb), immunoglobulin (Ig) G, and IgM, were assessed by mutually corroborated assays (ie, neutralization, enzyme-linked immunosorbent assay [ELISA], and microparticle chemiluminescence immunoassay [MCLIA]). Meanwhile, T-cell memory against SARS-CoV-2 spike, membrane, and nucleocapsid proteins was tested through enzyme-linked immunospot assay (ELISpot), intracellular cytokine staining, and tetramer staining-based flow cytometry, respectively. RESULTS: SARS-CoV-2-specific IgG antibodies, and NAb, can persist among >95% of COVID-19 convalescents from 6 to 12 months after disease onset. At least 19/71 (26%) of COVID-19 convalescents (double positive in ELISA and MCLIA) had detectable circulating IgM antibody against SARS-CoV-2 at 12 months post-disease onset. Notably, numbers of convalescents with positive SARS-CoV-2-specific T-cell responses (≥1 of the SARS-CoV-2 antigen S1, S2, M, and N proteins) were 71/76 (93%) and 67/73 (92%) at 6 and 12 months, respectively. Furthermore, both antibody and T-cell memory levels in the convalescents were positively associated with disease severity. CONCLUSIONS: SARS-CoV-2-specific cellular and humoral immunities are durable at least until 1 year after disease onset.

A COVID-19 T-Cell Response Detection Method Based on a Newly Identified Human CD8+ T Cell Epitope from SARS-CoV-2 - Hubei Province, China, 2021.

INTRODUCTION: Similar to antibody detection, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-specific T-cell response evaluation is also pivotal among the coronavirus disease 2019 (COVID-19) convalescents and the vaccinated populations. Nucleocapsid (N) protein is one of the main structural proteins of SARS-CoV-2 and can trigger T-cell responses in humans. METHODS: An overlapping peptide pool covering the full length of the N protein was designed, peptides with positive T-cell activating potency in COVID-19 convalescents were screened, and CD8+ T cell epitopes were further identified. The epitope was used to detect the SARS-CoV-2-specific CD8+ T cell responses in COVID-19 convalescents based in intracellular cytokine staining and tetramer staining in flow cytometry. RESULTS: A human leukocyte antigen A (HLA-A)*1101-restricted CD8+ T cell epitope, which could stimulate the production of IFN-γ via peripheral blood mononuclear cells (PBMCs) of the convalescents was defined, and the tetramer generated with this epitope could detect SARS-CoV-2-specific T cells in the PBMCs of the convalescents. The structural investigation eliminated that the epitope was a typical HLA-A*1101-restricted T-cell epitope which was conserved among all the sarbecoviruses. DISCUSSION: The newly identified SARS-CoV-2-derived T-cell epitope was helpful to detect the cellular immunity against different sarbecoviruses including SARS-CoV and SARS-CoV-2. This study provided an evaluation method and also a peptide candidate for the research and development of T-cell based vaccine for the virus.

Immune response pattern across the asymptomatic, symptomatic and convalescent periods of COVID-19.

We present an integrated analysis of urine and serum proteomics and clinical measurements in asymptomatic, mild/moderate, severe and convalescent cases of COVID-19. We identify the pattern of immune response during COVID-19 infection. The immune response is activated in asymptomatic infection, but is dysregulated in mild and severe COVID-19 patients. Our data suggest that the turning point depends on the function of myeloid cells and neutrophils. In addition, immune defects persist into the recovery stage, until 12 months after diagnosis. Moreover, disorders of cholesterol metabolism span the entire progression of the disease, starting from asymptomatic infection and lasting to recovery. Our data suggest that prolonged dysregulation of the immune response and cholesterol metabolism might be the pivotal causative agent of other potential sequelae. Our study provides a comprehensive understanding of COVID-19 immunopathogenesis, which is instructive for the development of early intervention strategies to ameliorate complex disease sequelae.