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:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could cause virulent infection leading to Corona Virus Disease 2019 (COVID-19)-related pneumonia as well as multiple organ injuries.HypothesisCOVID-19 infection may result in cardiovascular manifestations leading to worse clinical outcome.MethodsFifty four severe and critical patients with confirmed COVID-19 were enrolled. Risk factors predicting the severity of COVID-19 were analyzed.ResultsOf the 54 patients (56.1 ± 13.5 years old, 66.7% male) with COVID-19, 39 were diagnosed as severe and 15 as critical cases. The occurrence of diabetes, the level of D-dimer, inflammatory and cardiac markers in critical cases were significantly higher. Troponin I (TnI) elevation occurred in 42.6% of all the severe and critical patients. Three patients experienced hypotension at admission and were all diagnosed as critical cases consequently. Hypotension was found in one severe case and seven critical cases during hospitalization. Sinus tachycardia is the most common type of arrythmia and was observed in 23 severe patients and all the critical patients. Atrioventricular block and ventricular tachycardia were observed in critical patients at end stage while bradycardia and atrial fibrillation were less common. Mild pericardial effusion was observed in one severe case and five critical cases. Three critical cases suffered new onset of heart failure. Hypotension during treatment, severe myocardial injury and pericardial effusion were independent risk factors predicting the critical status of COVID-19 infection.ConclusionThis study has systemically observed the impact of COVID-19 on cardiovascular system, including myocardial injury, blood pressure, arrythmia and cardiac function in severe and critical cases. Monitoring of vital signs and cardiac function of COVID-19 patients and applying potential interventions especially for those with hypotension during treatment, severe myocardial injury or pericardial effusion, is of vital importance.
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:PURPOSE:COVID-19 patients requiring mechanical ventilation can overwhelm existing bed capacity. We aimed to better understand the factors that influence the trajectory of tracheostomy care in this population to facilitate capacity planning and improve outcomes. METHODS:We conducted an observational cohort study of patients in a high-volume centre in the worst-affected region of the UK including all patients that underwent tracheostomy for COVID-19 pneumonitis ventilatory wean from 1st March 2020 to 10th May 2020. The primary outcome was time from insertion to decannulation. The analysis utilised Cox regression to account for patients that are still progressing through their tracheostomy pathway. RESULTS:At the point of analysis, a median 21 days (IQR 15-28) post-tracheostomy and 39 days (IQR 32-45) post-intubation, 35/69 (57.4%) patients had been decannulated a median of 17 days (IQR 12-20.5) post-insertion. The overall median age was 55 (IQR 48-61) with a male-to-female ratio of 2:1. In Cox regression analysis, FiO2 at tracheostomy???0.4 (HR 1.80; 95% CI 0.89-3.60; p?=?0.048) and last pre-tracheostomy peak cough flow (HR 2.27; 95% CI 1.78-4.45; p?=?0.001) were independent variables associated with prolonged time to decannulation. CONCLUSION:Higher FiO2 at tracheostomy and higher pre-tracheostomy peak cough flow are associated with increased delay in COVID-19 tracheostomy patient decannulation. These finding comprise the most comprehensive report of COVID-19 tracheostomy decannulation to date and will assist service planning for future peaks of this pandemic.
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: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:Targeted therapeutics for SARS-CoV-2 virus caused COVID-19 are in urgent need. Chansu has been reported to have broad-spectrum antiviral effects and widely used in Southeast Asian countries. This study aims to assess the efficacy of Chansu injection in treating patients with severe COVID-19. A randomized preliminary clinical trial was conducted and eligible patients were allocated to receive general treatment plus Chansu injection or only general treatment as control for 7 days. The primary outcomes of the oxygenation index PaO2/FiO2 and ROX, secondary outcomes of white blood cell count, respiratory support step-down time (RSST), safety indicators, etc were monitored. After 7 days of treatment, the oxygenation index was improved in 95.2% patients in the treatment group compared with 68.4% in the control group. The PaO2/FiO2 and ROX indices in the treatment group (mean, 226.27±67.35 and 14.01±3.99 respectively) were significantly higher than the control group (mean, 143.23±51.29 and 9.64±5.54 respectively). The RSST was 1 day shorter in the treatment group. Multivariate regression analysis suggested that Chansu injection contributed the most to the outcome of PaO2/FiO2. No obvious adverse effects were observed. The preliminary data showed that Chansu injection had apparent efficacy in improving the respiratory function of patients with severe COVID-19.