DAC of The polarity and specificity of antiviral T lymphocyte responses determine susceptibility to SARS-CoV-2 infection in cancer patients and healthy individuals
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PROVIDER: EGAC00001002517 | EGA |
REPOSITORIES: EGA
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Project description:The goal of this study was to identify immune correlates of clinical protection against SARS-CoV-2 infection.
| EGAS00001005985 | EGA
Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other
Project description:ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m6 2A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20-009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m6 2A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.
| S-EPMC9513371 | biostudies-literature
Project description:During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
| S-EPMC7263513 | biostudies-literature
Project description:Severe acute respiratory coronavirus 2 (SARS-CoV-2) testing reagents are expected to become scarce worldwide. However, little is known regarding whether pooling of samples accurately detects SARS-CoV-2. To validate the feasibility of pooling samples, serial dilution analysis and spike-in experiments were conducted using synthetic DNA and nucleic acids extracted from SARS-CoV-2-positive and -negative patients. Furthermore, we studied 1000 individuals, 667 of whom were "healthy" individuals (195 healthcare workers and 472 hospitalized patients with disorders other than COVID-19 infection), and 333 infection-suspected patients with cough and fever. Serial dilution analysis showed a limit of detection of around 10-100 viral genome copies according to the protocol of the National Institute of Infectious Diseases, Japan. Spike-in experiments demonstrated that RT-qPCR detected positive signals in pooled samples with SARS-CoV-2-negative and -positive patients at 5-, 10-, 20-fold dilutions. By screening with this pooling strategy, by the end of April 2020 there were 12 SARS-CoV-2-positive patients in 333 infection-suspected patients (3.6%) and zero in 667 "healthy" controls. We obtained these results with a total of 538 runs using the pooling strategy, compared with 1000 standard runs. In a prospective study, we successfully detected SARS-CoV-2 using 10- to 20-fold diluted samples of nasopharyngeal swabs from eighteen COVID-19 patients with wide ranges of viral load. Pooling sample is feasible for conserving test reagents and detecting SARS-CoV-2 in clinical settings. This strategy will help us to research the prevalence infected individuals and provide infected-status information to prevent the spread of the virus and nosocomial transmission.
| S-EPMC7641135 | biostudies-literature
Project description:Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant recipients (KTXs). We found that, unlike healthy subjects, KTXs presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cell, SARS-CoV-2 receptor binding domain-specific memory B cell, and neutralizing antibody responses. KTXs also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals and suggest a GC origin for certain humoral and memory B cell responses following mRNA vaccination.
| S-EPMC8808747 | biostudies-literature
Project description:The global Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has affected more than eight million people. There is an urgent need to investigate how the adaptive immunity is established in COVID-19 patients. In this study, we profiled adaptive immune cells of PBMCs from recovered COVID-19 patients with varying disease severity using single-cell RNA and TCR/BCR V(D)J sequencing. The sequencing data revealed SARS-CoV-2-specific shuffling of adaptive immune repertories and COVID-19-induced remodeling of peripheral lymphocytes. Characterization of variations in the peripheral T and B cells from the COVID-19 patients revealed a positive correlation of humoral immune response and T-cell immune memory with disease severity. Sequencing and functional data revealed SARS-CoV-2-specific T-cell immune memory in the convalescent COVID-19 patients. Furthermore, we also identified novel antigens that are responsive in the convalescent patients. Altogether, our study reveals adaptive immune repertories underlying pathogenesis and recovery in severe versus mild COVID-19 patients, providing valuable information for potential vaccine and therapeutic development against SARS-CoV-2 infection.
| S-EPMC7426596 | biostudies-literature
Project description:Despite extensive research on SARS-CoV-2 vaccination responses in healthy individuals, there is comparatively little known beyond antibody titers and T-cell responses in the vulnerable cohort of patients after allogeneic hematopoietic stem cell transplantation (ASCT). In this study, we assessed the serological response and performed longitudinal multimodal analyses including T cell functionality and single-cell RNA sequencing combined with TCR/BCR profiling in the context of BNT162b2 vaccination in ASCT patients. In addition, these data were compared to publicly available data sets of healthy vaccinees. Protective antibody titers were achieved in 40% of patients. We identified a distorted B and T cell distribution, a reduced TCR diversity, and increased levels of exhaustion marker expression as possible causes for the poorer vaccine response rates in ASCT patients. IGHV gene rearrangement after vaccination proved to be highly variable in ASCT patients. Changes in TCRα and TCRβ gene rearrangement after vaccination differed from patterns observed in healthy vaccinees as well as unvaccinated ASCT patients and associated transplant donors. Crucially, ASCT patients elicited comparable proportions of SARS-CoV-2 vaccine-induced (VI) CD8+ T cells, characterized by a distinct gene expression pattern that is associated with SARS-CoV-2 specificity in healthy individuals. Our study underlines the impaired immune system and thus the lower vaccine response rates in ASCT patients. However, since protective vaccine responses and VI-CD8+ T cells can be induced in part of ASCT patients, our data advocate early post-transplant vaccination due to the high risk of infection in this vulnerable group.
2024-03-07 | GSE253948 | GEO
Project description:Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein–specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.
| S-EPMC9835846 | biostudies-literature
Project description:BackgroundThe impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored.MethodsAn observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination.ResultsAmong 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1β, IL-5, IL-7, and TNF-β was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1β was significantly higher in the TB/Prex-SCoV-2 group than the TB group.ConclusionTB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.
| S-EPMC11236595 | biostudies-literature