Project description:Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19-associated respiratory failure. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-associated pneumonia in the native lung. Most importantly, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report results of the first successful lung transplantation procedures in patients with non-resolving COVID-19-associated respiratory failure in the United States. We performed sm-FISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. We used a machine learning approach to project single cell RNA-Seq data from patients with late stage COVID-19 onto a single cell atlas of pulmonary fibrosis, revealing similarities across cell lineages. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.
Project description:Analysis of COVID-19 hospitalized patients, with different kind of symptoms, by human rectal swabs collection and 16S sequencing approach.
Project description:The identification of COVID-19 patients with high-risk of severe disease is a challenge in routine care. We performed blood RNA-seq gene expression analyses in severe hospitalized patients compared to healthy donors. Supervised and unsupervised analyses revealed a high abundance of CD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.
Project description:BACKGROUND:The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS:We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS:Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin (1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1? (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS:Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.
Project description:We isolated PBMC from healthy, moderate ( Oxygen supply < 10L/min), and severe (Oxygen supply >= 10L/min) COVID-19 patients after their admission to Intensive Care Units (ICU), at two timepoints (Day-1 and Day-4); and performed both CD14+ Monocyte enrichment followed by a Pan-DC kit to retrieve all Antigen Presenting Cell (APC) subsets from these age-matched patients. We performed single cell RNA sequencing using 10X technology on the single cell suspensions and constracted a high-resolution map of 81,643 Antigen Presenting Cells (APC) from the three COVID-19 severity groups. We were able to retrieve all the known six APC subsets and deciphered the altered pathways and ati-viral mechanisms, correlated with the disease severity.
Project description:The clinical course of Coronavirus disease 2019 (COVID-19) displays a wide variability, ranging from completely asymptomatic forms to diseases associated with severe clinical outcomes. To reduce the incidence COVID-19 severe outcomes, innovative molecular biomarkers are needed to improve the stratification of patients at the highest risk of mortality and to better customize therapeutic strategies. MicroRNAs associated with COVID-19 outcomes could allow quantifying the risk of severe outcomes and developing models for predicting outcomes, thus helping to customize the most aggressive therapeutic strategies for each patient. Here, we analyzed the circulating miRNA profiles in a set of 12 hospitalized patients with severe COVID-19, with the aim to identify miRNAs associated with in-hospital mortality.
Project description:We profiled the single-cell transcriptomes of 13,289 peripheral blood mononuclear cells isolated at three longitudinal stages from two severe COVID-19 patients treated with Tocilizumab. The raw sequencing data can be obtained from the Genome Sequence Archive for Human (GSA-Human) at https://bigd.big.ac.cn/gsa-human/browse/HRA000172 .
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Approximately 20% of infected patients experience a severe manifestation of the disease, causing bilateral pneumonia and acute respiratory distress syndrome. Severe COVID-19 patients also have a pronounced coagulopathy with approximately 30% of patients experiencing thromboembolic complications. However, the cellular etiology driving the coagulopathy remains unknown. Here, we explore whether the prominent neutrophilia seen in severe COVID-19 patients contributes to inflammation-associated coagulation. We found in severe patients the emergence of a CD16Int low-density inflammatory band (LDIB) neutrophil population that trends over time with changes in disease status. These cells demonstrated spontaneous neutrophil extracellular trap (NET) formation, higher phagocytic capacity, enhanced cytokine production, and associated clinically with D-dimer, ferritin, and systemic IL-6 and TNF-α levels. Strikingly, LDIB neutrophils are the major immune cells within the bronchoalveolar lavage (BAL) fluid with increased CXCR3 and loss of CD44 and CD38 expression. We conclude that the LDIB subset contributes to COVID- 19-associated coagulopathy (CAC) and systemic inflammation and could be used as an adjunct clinical marker to monitor disease status and progression. Identifying patients who are trending towards LDIB crisis and implementing early, appropriate treatment could improve all-cause mortality rates for severe COVID-19 patients.
Project description:The aim of this study was to describe the experiences of post-sedation COVID-19 patients in rehabilitation. Eleven Israeli men and women were interviewed in semi-structured interviews. They were patients recovering in a neurological rehabilitation unit from severe COVID-19 post-mechanical ventilation and sedation. Five themes were generated through thematic analysis: "an unexpected turn of events," "filling the gaps," "emotional reactions," "ambiguity regarding medical condition," and "sense and meaning-making." Findings suggest a need for improved communication between patients and medical staff to enhance a sense of control and coherence. Psychological support should be considered to facilitate sense and meaning-making processes during hospitalization.