SARS-CoV-2 infection in lung transplant recipients induces circulating exosomes with SARS-CoV-2 spike protein S2.
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ABSTRACT:
SUBMITTER: Bansal S
PROVIDER: S-EPMC8567032 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| EMPIAR-10947 | biostudies-other
Project description:BackgroundPrevious reports of coronavirus disease 2019 (COVID-19) following lung transplantation generally described a grim prognosis, but these were anecdotal case series of symptomatic patients. A systematic study of the outcomes and pathology of SARS-CoV-2 infection in a large cohort of lung transplant patients is lacking.MethodsTo determine the histopathologic evolution of COVID-19 in lung transplant recipients, we identified all patients who underwent surveillance transbronchial biopsies at our institution, tested positive for SARS-CoV-2, and had multiple pathology specimens available for evaluation. Histology was reviewed and immunofluorescence for SARS-CoV-2 nucleocapsid protein was performed.ResultsTen patients met inclusion criteria. Half (5/10) had incidental diagnosis on routine respiratory pathogen testing at the time of transbronchial biopsy. Six patients were hospitalized, with three requiring intensive care unit (ICU) admission. One patient died. Two specimens showed new onset International Society for Heart and Lung Transplantation (ISHLT) Grade A2 rejection at or following diagnosis. One patient developed bronchiolitis obliterans 111 days following diagnosis and 1 year post transplant. Two patients had organizing pneumonia at diagnosis and three patients showed evolving lung injury following diagnosis. The SARS-CoV-2 nucleocapsid protein was detected in a subset of samples at diagnosis and up to 111 days following diagnosis.ConclusionsOverall, the pathology of SARS-CoV-2 infection in lung transplant patients is varied, ranging from no pathologic alterations to organizing pneumonia and lung injury. The pathology findings did not necessarily correlate with clinical acuity, as one patient admitted to the ICU had normal pathology. These findings may be generalizable to non-transplant patients and require more follow-up regarding long-term outcomes.
| S-EPMC9115334 | biostudies-literature
Project description: Not available
| S-EPMC7790204 | biostudies-literature
Project description:Kidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of T-cell directed immunosuppression has been pursued. Here we evaluated the peripheral blood transcriptome of 64 KTRs either during and after acute COVID-19. We identified transcriptomic signatures of suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease. These findings were consistent with public data from non-KTR cohorts.
2022-07-15 | GSE195796 | GEO
Project description:Long-term success following human lung transplantation is poor due to chronic rejection. We demonstrated circulating exosomes of lung origin during acute and chronic lung allograft rejection. We analyzed plasma from pediatric lung transplant recipients (LTxRs) enrolled in the CTOT-C-03 to determine whether circulating exosomes are released into circulation during bronchiolitis obliterans syndrome (BOS). Plasma exosomes were isolated, and human leukocyte antigens (HLA) were detected. Exosomes were analyzed for lung self-antigens (SAgs), co-stimulatory molecules transcription factors, major histocompatibility complex class II (MHC-II), adhesion molecules, and 20S proteasome. Mice were immunized with exosomes from BOS or stable to determine their immunogenicity. Circulating exosomes from BOS LTxRs contained increased levels of SAgs, donor HLA class I, MHC-II, transcription factors, co-stimulatory molecules, and 20S proteasome compared with stable. Serial analysis of exosomes containing SAgs demonstrated that exosomes are detectable in the circulation before BOS. Mice immunized with exosomes from BOS, or stable, demonstrated that exosomes from BOS are distinct in inducing both humoral and cellular immune responses to SAgs. Circulating exosomes from BOS LTxRs elicit distinct humoral and cellular response. In addition, detection of SAgs on circulatory exosomes 12 months before diagnosis of BOS suggest that exosomes could serve as biomarker.
| S-EPMC8443129 | biostudies-literature
Project description:The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous loss worldwide. Although viral spike (S) protein binding of angiotensin-converting enzyme 2 (ACE2) has been established, the functional consequences of the initial receptor binding and the stepwise fusion process are not clear. By utilizing a cell-cell fusion system, in complement with a pseudoviral infection model, we found that the spike engagement of ACE2 primed the generation of S2' fragments in target cells, a key proteolytic event coupled with spike-mediated membrane fusion. Mutagenesis of an S2' cleavage site at the arginine (R) 815, but not an S2 cleavage site at arginine 685, was sufficient to prevent subsequent syncytia formation and infection in a variety of cell lines and primary cells isolated from human ACE2 knock-in mice. The requirement for S2' cleavage at the R815 site was also broadly shared by other SARS-CoV-2 spike variants, such as the Alpha, Beta, and Delta variants of concern. Thus, our study highlights an essential role for host receptor engagement and the key residue of spike for proteolytic activation, and uncovers a targetable mechanism for host cell infection by SARS-CoV-2.
| S-EPMC8740742 | biostudies-literature
Project description:Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes' response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes' involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19-associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers-such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component-were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes' significant contribution to several processes-such as inflammation, coagulation, and immunomodulation-during SARS-CoV-2 infection. The study's data are available via ProteomeXchange with the identifier PXD021144.
| S-EPMC7937875 | biostudies-literature
Project description:The recent manuscript reviewed investigations involving liver damage in coronavirus disease 2019 (COVID-19) patients, and COVID-19 in patients with previous chronic hepatological diseases, such as patients with liver graft. The literature presents several conflicting results concerning the anti-SARS-CoV-2 response in patients with solid organ transplants, in liver transplant recipients. Therefore, we would like to humbly state a few points for consideration involving liver transplant recipients and COVID-19, such as the time since transplantation, comorbidities, and immunosuppressive regimens.
| S-EPMC8641049 | biostudies-literature
Project description:ObjectiveImmunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV-2 in liver transplant (LT) recipients after COVID-19.DesignProspective multicentre case-control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV-2 and their neutralising activity in LT recipients with confirmed SARS-CoV-2 infection (COVID-19-LT) compared with immunocompetent patients (COVID-19-immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID-19-LT).ResultsOverall, 35 LT recipients were included in the COVID-19-LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19-immunocompetent and non-COVID-19-LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19-immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19-LT and COVID-19-immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19-immunocompetent cohort, p=0.024).ConclusionsOur findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV-2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.
| S-EPMC8753112 | biostudies-literature
Project description: Not available
| S-EPMC8280658 | biostudies-literature