Single-cell transcriptome of PBMC response to Omicron breakthrough infection
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PROVIDER: PRJNA1044775 | ENA |
REPOSITORIES: ENA
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Project description:To gain a deeper understanding of Omicron waves in the context of vaccination, we performed scRNA-seq together with single-cell V(D)J sequencing using PBMCs from nine Omicron breakthrough infection patients and six vaccinees to identify the possible cellular and molecular response mechanisms after breakthrough infection.
2024-12-18 | GSE248556 | GEO
Project description:There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long COVID and immune recovery after Omicron BTIs is crucial for understanding the disease and developing and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests and neutralization assay. Then, we applied proteomic analysis and single-cell RNA sequencing (scRNA-seq) to study the convalescents’ recovery status. Lastly, we retrospectively analyzed the clinical parameters related to immunity and metabolism of the convalescents. We found that major organs exhibited ephemeral dysfunction in double-Convidecia vaccinated persons who experienced BA.2 BTI and recovered to normal in approximately six-month. We observed durable and potent levels of neutralizing antibodies against major circulating severe acute respiratory syndrome coronavirus 2 sub-variants, including BQ.1, BQ.1.1 and BF.7, indicating that hybrid humoral immunity stays active. However, PLTs may take longer to recover. This was supported by proteomic and scRNA-seq analyses, which also showed coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then proved with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicators for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.
2023-08-16 | GSE240694 | GEO
Project description:The Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wild-type SARS-CoV-2. Omicron could not be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescent individuals who were infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8+ T cell epitopes, compared with Delta. These epitopes could induce robust CD8+ T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8+ T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted memory T cell responses. Consistently, a higher fraction of memory CD8+ T cells were found in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.
2023-03-11 | PXD037955 | Pride
Project description:Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon whether or not they were previously vaccinated or infected. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.
2022-06-11 | GSE201530 | GEO
Project description:Long-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study
| PRJNA1004627 | ENA
Project description:RNA-Seq was used to study changes in gene expression in saliva samples from 266 human subjects after SARS-COV-2 infection, vaccination, or combined infection and vaccination (breakthrough). Approximately equal numbers of males and females, matched for age, were profiled after subjects tested positive for COVID-19 by PCR and sequencing of the variant. In addition to samples from uninfected controls with and without vaccination, samples from infected subjects with and without vaccination that represent eight major SARS-COV-2 lineages are included: epsilon, iota, alpha, delta, omicron BA.1, omicron BA.2, omicron BA.4, and omicron BA.5. Stranded single-end sequencing was performed using standard Illumina protocols. Reads were quantified to hg38 human transcriptome using Salmon after adapter trimming. Quantified reads were filtered to remove features with fewer than one count in 80% of the samples, and normalized using TPM, followed by quantile and log2 transformation.
2023-09-19 | GSE212191 | GEO
Project description:There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long COVID and immune recovery after Omicron BTIs is crucial for understanding the disease and developing and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests and neutralization assay. Then, we applied proteomic analysis and single-cell RNA sequencing (scRNA-seq) to study the convalescents’ recovery status. Lastly, we retrospectively analyzed the clinical parameters related to immunity and metabolism of the convalescents. We found that major organs exhibited ephemeral dysfunction in double-Convidecia vaccinated persons who experienced BA.2 BTI and recovered to normal in approximately six-month. We observed durable and potent levels of neutralizing antibodies against major circulating severe acute respiratory syndrome coronavirus 2 sub-variants, including BQ.1, BQ.1.1 and BF.7, indicating that hybrid humoral immunity stays active. However, PLTs may take longer to recover. This was supported by proteomic and scRNA-seq analyses, which also showed coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then proved with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicators for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.
2023-08-08 | PXD044441 |
Project description:Memory B cells play a fundamental role in host defenses against viruses. This dataset aimed at understanding the recruitment and remodeling of the memory B cell repertoire in the context of BA.1-breakthrough infection in BNT162b2 mRNA vaccinated individuals. All four donors enrolled in the study had received a booster (3rd dose) of BNT162b2 mRNA vaccine and had no history of prior SARS-CoV-2 infection. All four experienced a documented breakthrough infection between 12/24/2021 and 01/30/2022 when BA.1 was responsible for > 85% of SARS-CoV-2 infections in France. All donors were sampled at Henri Mondor University Hospital (AP-HP, Paris France), and samples used for scRNA-seq were collected shortly after breakthrough infection (PO_M0 samples; between day 7 and day 18) and 5 to 6 months after infection (PO_M6 samples; between day 152 and day 173). Clinical and biological characteristics of these patients are summarized in the Patient_information.csv file. For each sample, an initial pool of 50.000 total peripheral CD3-CD14-CD56- CD19+ IgD- cells was always sorted and afterward, to enrich for cells of interest, only CD19+CD38low antibody secreting cells (ASCs), CD19hi IgD+ cells and SARS-CoV-2 Spike/RBD PE/tetramer positive B cells were sorted, leading to approximately 55000-60000 total sorted cells per sample. Sorted cells were then counted and up to 20 000 cells were loaded in the 10x Chromium Controller to generate single-cell gel-beads in emulsion. The scRNA-seq libraries for gene expression (mRNA), ADT and VDJ BCR libraries were generated using Chromium Next GEM Single Cell V(D)J Reagent Kit v.1.1 with Feature Barcoding (10x Genomics) according to the manufacturer’s protocol. PBMCs were initially isolated from venous blood samples via standard density gradient centrifugation and used after cryopreservation at -150°C. PBMCs were thawed using RPMI-1640 (Gibco) 10% FBS, washed twice and approximately 15x106 cells were then resuspended in 100µL PBS 2%FBS and incubated for 40 minutes at 4°C with a decoy tetramer (biotinylated Bovine Serum albumin coupled with BV785 streptavidin) and Hu-1 Spike, BA.1 Spike, Hu-1 RBD and BA.1 RBD tetramers (constructed using PE-labelled TotalSeqC® streptavidin with different barcodes for each individual antigens (see feature_reference.csv.gz files).). Cells were washed, resuspended in 100µL PBS 2%FBS and stained with a cocktail of fluorochrome conjugated (CD3, CD14 both APC-H7 at 1:100 each; CD15 and CD56 BV785 at 1:100 each, CD19 PECF594 at 1:100, IgD FITC at 1:100, CD38 PercP-Cy5.5 at 1:100) and TotalSeqC® (CD38, CD27, CD71, CD21, CD11c, CD39, FCRL5, CD95 all at 1:40 (all obtained from BioLegend)) antibodies for 40 minutes on ice. Viable cells were identified using a LIVE/DEAD Fixable Aqua Dead Cell Stain Kit (Thermo Fisher Scientific, 1:200) incubated with conjugated antibodies. Two distinct sorts were performed for each donor: one at the early time-point (PO_M0) and one at the 6 months’ time-point (PO_M6).
2023-08-15 | E-MTAB-12651 | biostudies-arrayexpress
Project description:BackgroundThe spread of the vaccine-resistant Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens unvaccinated and fully vaccinated individuals, and accelerated booster vaccination campaigns are underway to mitigate the ongoing wave of Omicron cases. The immunity provided by standard vaccine regimens, boosted regimens, and immune responses elicited by vaccination plus natural infection remain incompletely understood. The magnitude, quality, and durability of serological responses, and the likelihood of protection against future SARS-CoV-2 variants following these modes of exposure, are poorly characterized but are critical to the future trajectory of the coronavirus disease 2019 (COVID-19) pandemic.MethodsNinety-nine individuals were semi-randomly selected from a larger vaccination cohort following vaccination and, in some cases, breakthrough infection. We analyzed spike receptor-binding domain-specific immunoglobulin G (IgG), IgA, and IgM by enzyme-linked immunosorbent assay, neutralizing antibody titers against live SARS-CoV-2 variants, and antibody-dependent cell-mediated phagocytosis.FindingsIn 99 vaccinated adults, compared with responses after two doses of an mRNA regimen, the immune responses 3 months after a third vaccine dose and 1 month after breakthrough infection due to prior variants show dramatic increases in magnitude, potency, and breadth, including increased antibody-dependent cellular phagocytosis and robust neutralization of the currently circulating Omicron BA.2 variant.ConclusionsBoosters and natural infection substantially boost immune responses. As the number of Omicron sub-variant cases rise and as global vaccination and booster campaigns continue, an increasing proportion of the world's population will acquire potent immune responses that may be protective against future SARS-CoV-2 variants.FundingThis work was funded by the M. J. Murdock Charitable Trust, the OHSU Foundation, the NIH (T32HL083808), and OHSU Innovative IDEA.
| S-EPMC9492511 | biostudies-literature
Project description:Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by the SARS-CoV-2 Omicron sublineage BA.2 compared to BA.1. Here we show that without previous history of COVID-19, BA.2 infection induces a reduced immune response against all variants of concern (VOC) compared to BA.1 infection. The absence of ACE2 binding in sera of previously naïve BA.1 and BA.2 patients indicates a lack of meaningful neutralization. In contrast, anti-spike antibody levels and neutralizing activity greatly increased in the BA.1 and BA.2 patients with a previous history of COVID-19. Transcriptome analyses of peripheral immune cells showed significant differences in immune response and specific antibody generation between BA.1 and BA.2 patients as well as significant differences in the expression of specific immune genes. In summary, prior infection status significantly impacts the innate and adaptive immune response against VOC following BA.2 infection.
2022-12-20 | GSE205244 | GEO