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Prior BNT162b vaccination enhances interferon-JAK-STAT regulated antiviral programs in hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant

ABSTRACT: SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of Peripheral Blood Mononuclear Cells. Four patients had received the first dose of BNT162b about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. RNA-seq revealed an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase had subsided by day 35. Expression of the genes encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins was increased in the vaccinated group. We also investigated the immune transcriptome in naïve individuals receiving their first dose of BNT162b and identified a gene signature shared with the vaccinated COVID-19 patients. Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189039 | GEO | 2022/01/25

REPOSITORIES: GEO

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BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant

Project description:SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of peripheral blood immune cells. Four patients had received the first dose of BNT162b2 about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. RNA-seq reveals an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase subsides by day 35. Expression of the gene encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins increases in the vaccinated group. We also investigate the immune transcriptome in naïve individuals receiving their first dose of BNT162b2 and identify a gene signature shared with the vaccinated COVID-19 patients. Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b2 vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology.

2022-06-21 | GSE174621 | GEO

Next generation sequencing transcriptome analysis of patient-derived macrophages after SARS-CoV-2 mRNA vaccination

Project description:Innate immunity triggers responsible for viral control or hyperinflammation in COVID-19 are largely unknown. Recently we could show that the SARS-CoV-2 spike protein (S-protein) primes inflammasome formation and release of mature interleukin-1β (IL-1β) in macrophages derived from COVID-19 patients but not in macrophages from healthy SARS-CoV-2 naïve individuals (Theobald et al. EMBO Mol Med. 2021). Further analysis revealed that SARS-CoV-2 infection causes profound and long-lived reprogramming of macrophages resulting in augmented immunogenicity of the SARS-CoV-2 S-protein, a major vaccine antigen and potent driver of adaptive and innate immune signaling. In this project we want to focus on novel mRNA vaccines, which are exploiting S-protein driven immunogenicity for protection against SARS-CoV-2. Transcriptome analyses of macrophages might reveal differences in innate immune-associated pathways between vaccinated and unvaccinated individuals after prime-boost. Thus, our project could help to gain a better understanding of vaccine-induced immunity including underlying molecular mechanisms in the interaction of the innate and adaptive immune system after mRNA-based SARS-CoV-2 vaccination.

2022-05-02 | GSE200274 | GEO

A single-cell atlas of lymphocyte adaptive immune repertoires and transcriptomes reveals age-related differences in convalescent COVID-19 patients

Project description:We utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. Our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.

2021-03-20 | E-MTAB-10169 | biostudies-arrayexpress

Functional Assessment of US SARS-CoV-2 L452R Epsilon Variant

Project description:The multiple mutations comprising the epsilon variant demonstrates the independent convergent evolution of SARS-CoV-2 with its spike protein mutation L452R also present in the delta variant. Cells infected with live viral samples of the epsilon viral variant compared to non-epsilon variant displayed increased sensitivity to neutralization antibodies (NAb) suggesting an intact humoral response (P< 1.0 e-4). The ability for SARS-CoV2 to become more infectious but less virulent is supported mechanistically in the downregulation of viral processing pathways seen by multiomic analyses. Importantly, this paired transcriptomics and proteomic profiling of cellular response to live virus revealed an altered leukocyte response and metabolic mRNA processing in cells upon live viral infection of the epsilon variant. To ascertain host response to SARS-CoV-2 infection, primary COVID-19 positive nasopharyngeal samples were transcriptomically profiled a differential innate immune response (P<2.0 e-12) but, a relatively unaltered T cell response in the patients carrying the epsilon variant (P< 2.0 e-3). In fact, patients infected with SARS-CoV-2 and those vaccinated with the BNT162b2 vaccine have comparable CD4+/CD8+ T-cell immune responses to the B.1.429 variant (P<5 e-2). The epsilon variant alters viral processing response in infected cells, and the host innate immune response in COVID-19 positive nasopharyngeal swabs, but generates a protective host T cell response molecular signature in both vaccinated and unvaccinated patients.

2022-05-06 | PXD027995 | Pride

Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress

mRNA vaccine efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after the challenge

Project description:mRNA-1273, an mRNA-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is efficacious in mouse and non-human primate models of mild COVID-19. Hamsters exhibit more severe clinical disease from SARS-CoV-2, making it an important model to evaluate vaccine efficacy. Here we show that mock-vaccine treated hamsters infected with SARS-CoV-2 show weight loss and pulmonary infection with pathological changes and increased activated interstitial macrophages and other immune cell types. Prime-boost administration of mRNA-1273 elicited dose-independent robust binding and neutralizing antibodies, ameliorated weight loss and suppressed virus replication in the upper and lower airways. Vaccination largely prevented pulmonary pathological changes, antiviral immune cell activation and changes in cell type composition although increases in some immune cell types and activation of regulatory pathways were found and coincided with an anamnestic antibody response. The results characterize unexpected pulmonary cellular responses to SARS-CoV-2 in vaccinated animals that were shared but greatly attenuated, when compared to mock-vaccinated animals. The efficacy of mRNA-1273 is demonstrated as a two-dose vaccination schedule in a model of severe COVID-19.

2021-12-01 | GSE163838 | GEO

Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection

Project description: In this study, we elucidated defective viral genome generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from RNA-seq datasets of in vitro infections and autopsy lung tissues of COVID-19 patients.

2023-07-05 | GSE222381 | GEO

Linear epitope-specific IgG responses to SARS-CoV-2 and related human coronaviruses in human COVID-19 convalescent sera

Project description:The on-going COVID-19 pandemic requires a deeper understanding of the long-term antibody responses that persist following SARS-CoV-2 infection. To that end, we determined epitope-specific IgG antibody responses in COVID-19 convalescent sera collected at 5 months post-diagnosis and compared that to sera from naïve individuals. Each serum sample was reacted with a high-density peptide microarray representing the complete proteome of SARS-CoV-2 as 15 mer peptides with 11 amino acid overlap and homologs of spike glycoprotein, nucleoprotein, membrane protein, and envelope small membrane protein from related human coronaviruses. Binding signatures were compared between COVID-19 convalescent patients and naïve individuals using the web service tool EPIphany.

2022-02-05 | E-MTAB-10740 | biostudies-arrayexpress

TRB sequences targeting ORF1ab are associated with disease severity in hospitalized COVID-19 patients

Project description:The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T cell response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor Beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to the severity of the disease course. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 785 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 140 SARS-CoV-2 specific TRB sequences belonging to 119 clusters in our COVID-19 patients. Next, we investigated 92 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences towards the nonstructural proteins (NSPs) of ORF1a/b of the SARS-CoV-2 genome was observed in clusters with critical disease course when compared to COVID-19 clusters with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from nonstructural proteins of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.

2021-07-07 | GSE161810 | GEO

Immunological Signatures Driving COVID-19 Severity in Ghanaians: Insights from Upper Airway Transcriptome Analysis

Project description:The immunological signatures driving COVID-19 severity in Ghanaians are not well understood. We, therefore, performed bulk transcriptome sequencing of nasopharyngeal samples from SARS-CoV-2-infected Ghanaians with mild and severe COVID-19 and healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identified drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls. COVID-19 severity was associated with a dysregulated inflammatory response occasioned by overexpression of IL1A, S100A7, CRNN, and IL23A proinflammatory cytokines and hyperactivation of the NF-κB pathway through MAL signaling. SAMD9L was also among the differentially regulated interferon-stimulated genes (ISGs) in our mild and severe disease cohorts, suggesting that it may be playing a critical role in SARS-CoV-2 pathogenesis. We noted differences in antiviral gene expression by comparing our data with a publicly available dataset from a non-African (Indians) (GSE166530) cohort. Overall, the study identifies immune signatures driving COVID-19 severity in Ghanaians that could serve as potential prognostic markers. It further provides preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub-Saharan Africans (Ghanaians) and non-Africans (Indians), which could be contributing to the differences in disease outcomes. Further studies using a larger dataset from different populations will expand on these findings. Keywords: Nasopharyngeal swab, SARS-Cov-2, RNA-Seq, Ghanaians, immunological signatures

2023-08-07 | GSE215906 | GEO

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