Project description:Understanding on pathogenesis of COVID-19 is rapidly growing, but primary target cells of SARS-CoV-2 infection is still not known. Here, we performed single cell RNA sequencing on human nasal swab from COVID-19 patient to investigate the expression patterns of host cell entry factors of SARS-CoV-2.
Project description:Understanding on pathogenesis of COVID-19 is rapidly growing, but primary target cells of SARS-CoV-2 infection is still not known. Here, we performed single cell RNA sequencing on human nasal swab from healthy donors to investigate the expression patterns of host cell entry factors of SARS-CoV-2.
Project description:To elucidate key pathways in the host transcriptome of patients infected with SARS-CoV-2, we used RNA sequencing (RNA Seq) to analyze nasopharyngeal (NP) swab and whole blood (WB) samples from 333 COVID-19 patients and controls, including patients with other viral and bacterial infections. Analyses of differentially expressed genes (DEGs) and pathways was performed relative to other infections (e.g. influenza, other seasonal coronaviruses, bacterial sepsis) in both NP swabs and WB. Comparative COVID-19 host responses between NP swabs and WB were examined. Both hospitalized patients and outpatients exhibited upregulation of interferon-associated pathways, although heightened and more robust inflammatory and immune responses were observed in hospitalized patients with more clinically severe disease. A two-layer machine learning-based classifier, run on an independent test set of NP swab samples, was able to discriminate between COVID-19 and non-COVID-19 infectious or non-infectious acute respiratory illness using complete (>1,000 genes), medium (<100) and small (<20) gene biomarker panels with 85.1%-86.5% accuracy, respectively. These findings demonstrate that SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for differential diagnosis of COVID-19 disease.
Project description:<p><strong>INTRODUCTION:</strong> COVID-19 has become a global impediment by bringing everything to a halt starting from January 2020. India underwent the lockdown starting from 22nd March 2020 with the sudden spike in the number of COVID-19 patients in major cities and states. This study focused on how metabolites play a crucial role in SARSCoV-2 prognosis.</p><p><strong>MATERIALS AND METHODS:</strong> Metabolome profiling of 106 plasma samples and 24 swab samples from symptomatic patients in the Indian population of the Mumbai region was done. COVID-19 positive samples were further segregated under the non-severe COVID-19 and severe COVID-19 patient cohort for both plasma and swab.</p><p><strong>RESULTS:</strong> After analyzing the raw files, total 7,949 and 12,871 metabolites in plasma and swab were found. 11 and 35 significantly altered metabolites were found in COVID-19 positive compared to COVID-19 negative plasma and swab samples, respectively. Also, 9 and 23 significantly altered metabolites were found in severe COVID-19 positive to non-severe COVID-19 positive plasma and swab samples, respectively. The majorly affected pathways in COVID-19 patients were found to be the amino acid metabolism pathway, sphingosine metabolism pathway, and bile salt metabolism pathway.</p><p><strong>CONCLUSION:</strong> This study facilitates identification of potential metabolite-based biomarker candidates for rapid diagnosis and prognosis for clinical applications.</p><p><br></p><p><strong>Nasopharyngeal swab assay</strong> is reported in the current study <strong>MTBLS2349</strong>.</p><p><strong>Blood plasma assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS2291' rel='noopener noreferrer' target='_blank'><strong>MTBLS2291</strong></a>.</p>
Project description:Coronavirus disease 2019 (COVID-19) has been threatening public health for the last 3 years globally. So far, the pathophysiology of the disease and therapeutic strategies have not clearly known yet. In this project, performing label-free plasma proteomics analysis, we aimed at identifying severity biomarkers for COVID-19 prognosis and proposing potential drugs against the disease symptoms by building the signaling network of significantly regulated proteins and finding the corresponding virus-host interactions. A total of 38 plasma samples from 13 COVID-19 PCR positive individuals and 5 plasma samples from healthy individuals were collected for the analysis. According to the WHO criteria, the severity of our patients was categorized as moderate (n=4), severe (n=3), and critical (n=6). Also, blood samples were collected in different time points after the symptom onset: (1) 1-5 day (± 2 days); early infection, (2) 5-15 days (± 2 days); inflammatory response, and after 15 days (± 2 days); recovery which shows the first PCR negative result from a nasal swab. In summary, we found significantly regulated proteins between COVID-19 patients and uninfected individuals and proposed some critical patient-specific prognostic biomarkers, which can be used as an early predictor of the disease severity. Also, we created a COVID-19 related plasma protein network modulated by SARS-CoV2 viral proteins and indicated clinically significant targets for the disease symptoms.
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.
Project description:COVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unraveling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls.
Project description:In this prospective observational cohort study, we found transcriptional evidence that persistent immune dysfunction was associated with 28-day mortality in both COVID-19 and non-COVID-19 septic patients. COVID-19 patients had an early antiviral response but became indistinguishable on a gene expression level from non-COVID-19 sepsis patients a week later. Early treatment of COVID-19 and non-COVID-19 sepsis ICU patients should focus on pathogen control, but both patient groups also require novel immunomodulatory treatments, particularly later during ICU hospitalization, independent of admission diagnosis. Some T1 samples were uploaded in GSE185263 and were not re-uploaded in this series.
Project description:<p><strong>INTRODUCTION:</strong> COVID-19 has become a global impediment by bringing everything to a halt starting from January 2020. India underwent the lockdown starting from 22nd March 2020 with the sudden spike in the number of COVID-19 patients in major cities and states. This study focused on how metabolites play a crucial role in SARSCoV-2 prognosis.</p><p><strong>MATERIALS AND METHODS:</strong> Metabolome profiling of 106 plasma samples and 24 swab samples from symptomatic patients in the Indian population of the Mumbai region was done. COVID-19 positive samples were further segregated under the non-severe COVID-19 and severe COVID-19 patient cohort for both plasma and swab.</p><p><strong>RESULTS:</strong> After analyzing the raw files, total 7,949 and 12,871 metabolites in plasma and swab were found. 11 and 35 significantly altered metabolites were found in COVID-19 positive compared to COVID-19 negative plasma and swab samples, respectively. Also, 9 and 23 significantly altered metabolites were found in severe COVID-19 positive to non-severe COVID-19 positive plasma and swab samples, respectively. The majorly affected pathways in COVID-19 patients were found to be the amino acid metabolism pathway, sphingosine metabolism pathway, and bile salt metabolism pathway.</p><p><strong>CONCLUSION:</strong> This study facilitates identification of potential metabolite-based biomarker candidates for rapid diagnosis and prognosis for clinical applications.</p><p><br></p><p><strong>Blood plasma assay</strong> is reported in the current study <strong>MTBLS2291</strong>.</p><p><strong>Nasopharyngeal swab assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS2349' rel='noopener noreferrer' target='_blank'><strong>MTBLS2349</strong></a>.</p>
Project description:Risk of severe disease and death due to coronavirus 2019 (COVID-19) is increased in certain patient demographic groups, including those who are of advanced age, male sex, and obese body mass index. Investigations of the biological variations that contribute to this risk have been hampered by heterogeneous severity, with immunologic features of critical disease potentially obscuring differences between risk groups. To examine immune heterogeneity related to demographic risk factors, we enrolled 38 patients hospitalized with clinically homogeneous COVID-19 pneumonia – defined as oxygen saturation <94% on room air without respiratory failure, septic shock, or multiple organ dysfunction – and performed single-cell RNA-sequencing of leukocytes collected at admission. Examination of individual risk factors identified strong shifts within neutrophil and monocyte/dendritic cell compartments, revealing altered immune cell type-specific responses in higher-risk COVID-19 patient subgroups. Specifically, we found transcriptional evidence of altered neutrophil maturation in aged versus young patients and enhanced cytokine responses in monocytes/dendritic cells of male versus female patients. Such innate immune cell alterations may contribute to outcome differences linked to these risk factors. They also highlight the importance of diverse patient cohorts in studies of therapies targeting the immune response in COVID-19.