scholarly journals Persistence of viral RNA, widespread thrombosis and abnormal cellular syncytia are hallmarks of COVID-19 lung pathology

Author(s):  
Rossana Bussani ◽  
Edoardo Schneider ◽  
Lorena Zentilin ◽  
Chiara Collesi ◽  
Hashim Ali ◽  
...  

ABSTRACTCOVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombosis of the lung micro- and macro-vasculature. Thrombi were in different stages of organization, consistent with an ongoing, endogenous thrombotic process. In all the analyzed samples, in situ RNA hybridization showed that pneumocytes and vascular endothelial cells had massive presence of viral RNA even at the later stages of the disease. An additional feature of the disease was the presence, in the vast majority of patients, of a large number of dysmorphic pneumocytes, often forming large syncytial elements, a consequence of the fusogenic activity of the viral Spike protein, detected with specific antibodies. Despite occasional presence of virus-positive cells in the heart, no overt signs of viral infection were detected in other organs, which showed common alterations compatible with prolonged hypoxia, multifocal organ disease or previous comorbidities. In summary, COVID-19 is a unique interstitial pneumonia with extensive lung thrombosis, long-term persistence of viral replication in pneumocytes and endothelial cells, along with the presence of infected cellular syncytia in the lung. We propose that several of the COVID-19 disease features are due to the persistence of virus-infected cells in the lungs of the infected individuals for the duration of the disease.

2012 ◽  
Vol 554-556 ◽  
pp. 1650-1655 ◽  
Author(s):  
Xue Mei Han ◽  
Hong Tao Wei ◽  
Song Yan Liu

Abstract Objective To investigate the expression of erythropoietin (EPO) after acupuncture preconditioning plus focal cerebral ischemia treatment. Methods Rat focal cerebral ischemia model and acupuncture preconditioning model were established. Animals were randomly assigned into different groups: control (focal cerebral ischemia) and acupuncture preconditioning plus focal cerebral ischemia, with 8 rats for each group. The expression of EPO after different treatments was determined by histological examination, immunohistochemistry and in situ hybridization. Results The mRNA and protein expressions of EPO could be detected in survival and necrotic neurons, glia as well as vascular endothelial cells. Focal cerebral ischemia promoted the expression of EPO. Significant enhanced EPO level was found in the ischemic peripheral zone after acupuncture preconditioning (P < 0.05). Conclusion Our results demonstrated that acupuncture preconditioning enhanced the expression of EPO in neurons, glia and vascular endothelial cells the ischemic peripheral zone, suggesting the involvement of EPO in acupuncture preconditioning-induced neuroprotection following focal cerebral ischemia. EPO may exert neuroprotective effects through promoting neurotrophic support and angiogenesis.


2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 35-40 ◽  
Author(s):  
Moon Jeong Seo ◽  
Suk Joong Oh ◽  
Sung Il Kim ◽  
Kye Won Cho ◽  
Inho Jo ◽  
...  

♦ Objective Increased peritoneal vasculature has been reported in long-term peritoneal dialysis (PD), and vascular endothelial growth factors (VEGFs) have been found in dialysate. High concentrations of glucose or lactate, glucose degradation products (GDPs), and low pH of dialysis solutions are all possible factors in increased peritoneal VEGF synthesis. In this study, we investigated the effects of high glucose dialysis solutions on VEGF synthesis by peritoneal vascular endothelial cells (PVECs). ♦ Methods The PVECs were isolated from rat omentum and were incubated for 4 hours in three different culture media [M199 media (control), conventional dialysis solutions containing 4.25% glucose diluted with an equal volume of M199 media (HGD), and M199 media containing 118 mmol/L mannitol as an osmolar control (mannitol)]. Levels of VEGF protein in the culture supernatant were measured by ELISA, and mRNA expression was determined by Northern blot analysis. Data are presented as percent of control. ♦ Results After incubation for 4 hours, the number of cells did not differ between the 3 groups. Levels of VEGF in culture supernatant were significantly higher in the HGD group (124% ± 19%, p = 0.006) as compared with the control and mannitol (85% ± 10%) groups. The mRNA expression of VEGF appeared to be higher in the HGD group (128% ± 49%) than in the control and mannitol (94% ± 18%) groups. ♦ Conclusion High glucose dialysis solutions increased VEGF synthesis by PVECs. The relationship between VEGF synthesis by PVECs and neovascularization of the peritoneum observed in long-term peritoneal dialysis patients has to be studied further.


1983 ◽  
Vol 97 (2) ◽  
pp. 416-424 ◽  
Author(s):  
G E White ◽  
M A Gimbrone ◽  
K Fujiwara

The organization of actin and myosin in vascular endothelial cells in situ was studied by immunofluorescence microscopy. Examination of perfusion-fixed, whole mounts of normal mouse and rat descending thoracic aorta revealed the presence of axially oriented stress fibers containing both actin and myosin within the endothelial cells. In both species, the proportion of cells containing stress fibers varied from region to region within the same vessel. Some endothelial cells in mouse mesenteric vein and in rat inferior vena cava also contained stress fibers. Quantitative studies of the proportion of endothelial cells containing stress fibers in the descending thoracic aorta of age-matched normotensive and spontaneously hypertensive rats revealed significant differences. When animals of the same sex of the two strains were compared, the proportion was approximately two times greater in the spontaneously hypertensive rats. The proportion of endothelial cells containing stress fibers was about two times greater in males than in females of both strains. These observations suggest that multiple factors, including anatomical, sex, and hemodynamic differences, influence the organization of the endothelial cell cytoskeleton in situ.


2004 ◽  
Vol 85 (4) ◽  
pp. 1029-1037 ◽  
Author(s):  
Emmanuelle Bensaude ◽  
Jane L. E. Turner ◽  
Philip R. Wakeley ◽  
David A. Sweetman ◽  
Claire Pardieu ◽  
...  

Infection with virulent strains of classical swine fever virus (CSFV) results in an acute haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopenia and immunosuppression, whereas for less virulent isolates infection can become chronic. In view of the haemorrhagic pathology of the disease, the effects of the virus on vascular endothelial cells was studied by using relative quantitative PCR and ELISA. Following infection, there was an initial and short-lived increase in the transcript levels of the proinflammatory cytokines interleukins 1, 6 and 8 at 3 h followed by a second more sustained increase 24 h post-infection. Transcription levels for the coagulation factor, tissue factor and vascular endothelial cell growth factor involved in endothelial cell permeability were also increased. Increases in these factors correlated with activation of the transcription factor NF-κB. Interestingly, the virus produced a chronic infection of endothelial cells and infected cells were unable to produce type I interferon. Infected cells were also protected from apoptosis induced by synthetic ouble-stranded RNA. These results demonstrate that, in common with the related pestivirus bovine viral diarrhoea virus, CSFV can actively block anti-viral and apoptotic responses and this may contribute to virus persistence. They also point to a central role for infection of vascular endothelial cells during the pathogenesis of the disease, where a proinflammatory and procoagulant endothelium induced by the virus may disrupt the haemostatic balance and lead to the coagulation and thrombosis seen in acute disease.


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