Single cell RNA and immune repertoire profiling of COVID-19 patients reveal novel neutralizing antibody.
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ABSTRACT:
SUBMITTER: Li F
PROVIDER: S-EPMC7686823 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant "escape" mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.
| S-EPMC8067572 | biostudies-literature
Project description:BackgroundAlthough there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets' analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses.MethodsIn this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed.ResultsThe white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells.ConclusionOur results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.
| S-EPMC8256640 | biostudies-literature
Project description:While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.
| S-EPMC8443960 | biostudies-literature
Project description:Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration's (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31-35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was ~93% (PRNT50) and ~54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 ELISA titers) showed maximal activity, but not all high titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.
| S-EPMC7665673 | biostudies-literature
Project description:COVID-19 is a viral infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized by a complex inflammatory process and clinical immunophenotypes. Nowadays, several alterations of immune response within the respiratory tracts as well as at the level of the peripheral blood have been well documented. Nonetheless, their effects on COVID-19-related cell heterogeneity and disease progression are less defined. Here, we performed a single-cell RNA sequencing of about 400 transcripts relevant to immune cell function including surface markers, in mononuclear cells (PBMCs) from the peripheral blood of 50 subjects, infected with SARS-CoV-2 at the diagnosis and 27 healthy blood donors as control. We found that patients with COVID-19 exhibited an increase in COVID-specific surface markers in different subsets of immune cell composition. Interestingly, the expression of cell receptors, such as IFNGR1 and CXCR4, was reduced in response to the viral infection and associated with the inhibition of the related signaling pathways and immune functions. These results highlight novel immunoreceptors, selectively expressed in COVID-19 patients, which affect the immune functionality and are correlated with clinical outcomes.
| S-EPMC8698462 | biostudies-literature
Project description:The SARS-CoV-2 virus's ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients' organ samples. Various levels of severity of infection were accounted for, with comparative analyses between mild, moderate, and severely infected patients. Our analysis uncovered an upregulation of the innate immune response via several inflammatory genes, IL-2, IL-6, IL-8, IL-17A, and NF-κB. Consequently, we found that the upregulation of these downstream effects can lead to organ injury. The downregulated pathways such as eukaryotic initiation factor 2 (eIF2) and eIF4-mediated host translation, were found to lead to an increased viral translation. We also found that the loss of inhibitory peptides can suppress an overactive innate immune response via NF-κB and interleukin-mediated pathways. Investigation of viral-host protein mapping showed that the interaction of viral proteins with host proteins correlated with the down- and upregulation of host pathways such as decreased eIF2-mediated host translation and increased hypertrophy and fibrosis. Inflammation was increased via the stimulation of pro-inflammatory cytokines and suppression of host translation pathways that led to reduced inflammatory inhibitors. Cardiac hypertrophy and organ fibrosis were the results of increased inflammation in organs of severe and critical patients. Finally, we identified potential therapeutic targets for the treatment of COVID-19 and its deleterious effects on organs. Further experimental investigation would conclusively determine the effects of COVID-19 infection on organs other than the lungs and the effectiveness of the proposed therapeutic targets.
| S-EPMC8706409 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global crisis; however, our current understanding of the host immune response to SARS-CoV-2 infection remains limited. Herein, we performed RNA sequencing using peripheral blood from acute and convalescent patients and interrogated the dynamic changes of adaptive immune response to SARS-CoV-2 infection over time. Our results revealed numerous alterations in these cohorts in terms of gene expression profiles and the features of immune repertoire. Moreover, a machine learning method was developed and resulted in the identification of five independent biomarkers and a collection of biomarkers that could accurately differentiate and predict the development of COVID-19. Interestingly, the increased expression of one of these biomarkers, UCHL1, a molecule related to nervous system damage, was associated with the clustering of severe symptoms. Importantly, analyses on immune repertoire metrics revealed the distinct kinetics of T-cell and B-cell responses to SARS-CoV-2 infection, with B-cell response plateaued in the acute phase and declined thereafter, whereas T-cell response can be maintained for up to 6 months post-infection onset and T-cell clonality was positively correlated with the serum level of anti-SARS-CoV-2 IgG. Together, the significantly altered genes or biomarkers, as well as the abnormally high levels of B-cell response in acute infection, may contribute to the pathogenesis of COVID-19 through mediating inflammation and immune responses, whereas prolonged T-cell response in the convalescents might help these patients in preventing reinfection. Thus, our findings could provide insight into the underlying molecular mechanism of host immune response to COVID-19 and facilitate the development of novel therapeutic strategies and effective vaccines.
| S-EPMC8421539 | biostudies-literature
Project description:Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire-pre- and post-vaccination-and select several antibody clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen.
| S-EPMC6591005 | biostudies-literature
Project description:Multi-omics single-cell profiling of surface proteins, gene expression and lymphocyte immune receptors from hospitalised COVID-19 patient peripheral blood immune cells and healthy controls donors. Identification of the coordinated immune cell compositional and state changes in response to SARS-CoV-2 infection or LPS challenge, compared to healthy control immune cells.
2021-03-17 | E-MTAB-10026 | biostudies-arrayexpress
Project description: Not available
| S-BSST416 | biostudies-other