Project description:The morbidity and mortality of lung cancer are increasing. The Corona Virus Disease 2019 (COVID-19) is caused by novel coronavirus 2019-nCoV-2, leading to subsequent pulmonary interstitial fibrosis with chronic inflammatory changes, e.g., inflammatory factors repeatedly continuously stimulating and attacking the alveolar epithelial cells. Meanwhile, 2019-nCoV-2 can activate PI3K/Akt and ERK signaling pathways, which can play the double roles as both anti-inflammatory and carcinogenic factors. Moreover, hypoxemia may be developed, resulting in the up-regulation of HIF-1 α expression, which can be involved in the occurrence, angiogenesis, invasion and metastasis of lung cancer. Additionally, the immune system in 2019-nCoV-2 infected cases can be suppressed to cause tumor immune evasion. Therefore, we speculate that COVID-19 may be a risk factor of secondary lung cancer.
Project description:Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism. In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.
Project description:Background: Amid the coronavirus disease 2019 (COVID-19) pandemic, we analyzed clinical characteristics of acute lung injury (ALI) in COVID-19 patients and reported their similarity and dissimilarity to those of non-COVID-19 patients in the intensive care unit (ICU). Methods: We reported on 90 COVID-19 and 130 non-COVID-19 ALI patients in the ICUs of multiple centers. Demographic data, medical histories, laboratory findings, and radiological images were analyzed and compared between the two cohorts and within each cohort between survivors and non-survivors. For ALI survivors, clinical characteristics before and after treatment were also compared. Findings: Aberrations in blood parameters, such as leukocytosis, neutrophilia, and thrombocytopenia, were observed in both cohorts. More characteristic abnormalities, including significantly higher red cell distribution width (RDW), C-reactive proteins, and lactic dehydrogenase (LDH) but lower troponin (TnT) and procalcitonin, were observed in the COVID-19 cohort than in the non-COVID-19 cohort, whereas D-dimer levels showed a similar elevation in both cohorts. The COVID-19 cohort also showed more diversified CT patterns where severe features such as consolidations and crazy paving patterns were more frequently observed. Multivariate analysis indicated that age, fever symptom, prothrombin time, procalcitonin, partial pressure of carbon dioxide, oxygenated hemoglobin, and crazy paving patterns in CT scans were independent risk factors associated with COVID-19. Interpretation: Comparison of ALI characteristics between COVID-19 and non-COVID-19 patients in the ICU setting provided insight into the pathogenesis of ALI induced by different risk factors, suggesting distinct treatment plans.
Project description:We profiled 116,314 cells using snRNA-seq of 20 frozen lungs obtained from 19 COVID-19 decedents and seven control patients with short postmortem interval (PMI) autopsies. The COVID-19 cohort comprises seven female and 12 male decedents, including 13 patients of Hispanic ethnicity, with an age range from 58 to >89 years who had acquired SARS-CoV-2 infection and succumbed to the disease. The average time from symptom onset to death was 27.5 days (range, 4–63 days). After rapid autopsy with a median PMI of 4 hours (range 2–9 hours) collected tissues were either flash-frozen or frozen following OCT (optimal cutting temperature) embedment and subjected to snRNA-seq using a droplet-based platform (10x Genomics). All included patients had underlying hypertensive disorder and frequently one or more additional co-morbidities associated with increased risk for severe COVID-19.
Project description:An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.
Project description:Metatranscriptomic analysis identifies a state of pathogen dominance and suppressed pulmonary immune signaling in critically ill COVID-19 patients with secondary bacterial pneumonia.
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.