Project description:Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.
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:BACKGROUND:The prevalence of heart failure (HF) is increasing substantially and, despite improvements in medical therapy, HF still carries a poor prognosis. Mechanical circulatory support (MCS) by a continuous-flow left ventricular assist device (cf-LVAD) improves survival and quality of life in selected patients. This holds especially for the short-term outcome, but experience regarding long-term outcome is growing as the waiting time for heart transplantation is increasing due to the shortage of donor hearts. Here we present our results from the University Medical Centre Utrecht. METHODS:Data of all patients with a cf-LVAD implant between March 2006 and January 2018 were collected. The primary outcome was survival. Secondary outcomes included adverse events defined according to the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definitions, described per patient year. RESULTS:A total of 268 patients (69% male, mean age 50?±?13 years) received a cf-LVAD. After a median follow-up of 542 (interquartile range 205-1044) days, heart transplantation had been performed in 82 (31%) patients, the cf-LVAD had been explanted in 8 (3%) and 71 (26%) had died. Survival at 1, 3 and 5 years was 83%, 72% and 57%, respectively, with heart transplantation, cf-LVAD explantation or death as the end-point. Death was most often caused by neurological complications (31%) or infection (20%). Major bleeding occurred 0.51 times and stroke 0.15 times per patient year. CONCLUSION:Not only short-term results but also 5?year survival after cf-LVAD support demonstrate that MCS is a promising therapy as an extended bridge to heart transplantation. However, the incidence of several major complications still has to be addressed.