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2.
Journal of Heart & Lung Transplantation ; 42(4):S260-S260, 2023.
Article in English | Academic Search Complete | ID: covidwho-2270201

ABSTRACT

Due to chronic immunosuppression and frequent comorbidities, severe infection with Covid-19 is common among heart transplant recipients. Heart transplant recipients with Covid-19 have a short-term mortality rate as high as 25% and hospitalization rates as high as 77%. These patients generally have a severe course of infection and present with right ventricular dysfunction, arrhythmias, and thromboembolic events. We present the case of a heart transplant recipient who presented with Covid-19 infection who, despite initial improvement, eventually passed from severe coronary vasculopathy. The incidence of vasculopathy six months post-transplant without coexisting infection is extremely uncommon. A 45-year-old male with end stage heart failure due to non ischemic cardiomyopathy underwent heart transplant in July 2021. Post-transplant, the patient was clinically stable with LVEF of 60-65%. In January 2022, the patient was admitted for cardiogenic shock with multi-organ failure and tested positive for Covid-19. His echo showed an LVEF of 20-25%. Inotrope therapy was initiated and an intra-aortic balloon pump was placed. Hemodialysis was begun due to oliguria and acute renal failure. RV biopsy indicated moderate acute T-cell mediated rejection and was treated appropriately. Prior to discharge following his six week hospitalization, pathology was negative for rejection and his LVEF increased to 50%. 3 weeks later, he was found unresponsive at home and pronounced dead by EMS. Autopsy determined that the cause of death was sudden cardiac death due to Covid-19. Autopsy Report: " The cause of death is sudden cardiac death secondary to a rapidly progressive graft vasculopathy with concomitant endothelitis and positive staining of endothelium for SARS-CoV-2 viral nucleoprotein, with consequent diffuse myocardial necrosis." The kidneys were enlarged with findings indicating Acute Tubular Necrosis. Our patient presented six months post-transplant with severe Covid-19 induced coronary vasculopathy which progressed to sudden cardiac death. This case demonstrates the importance of preventing Covid-19 infection among heart transplant recipients and the need to assess these patients for coronary vasculopathy prior to progression to sudden cardiac death. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

3.
European Respiratory Journal Conference: European Respiratory Society International Congress, ERS ; 60(Supplement 66), 2022.
Article in English | EMBASE | ID: covidwho-2265355

ABSTRACT

Background: In COVID-19 survivors, there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood. Aims and objectives: In this study, we aimed to gain insights into the evolution of pulmonary fibrogenesis in COVID19. Method(s): In this multicentric study, n=12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within <=7 and >7 days of hospitalization, respectively) and compared to n=11 healthy controls;mRNA and protein expression were analyzed using a fibrosis-specific panel and immunostaining. Biological pathway analysis was performed using two different gene expression databases. Result(s): Median duration of hospitalization until death was 3 (IQR25-75, 3-3.75) and 14 (12.5-14) days in the early and late group, respectively. Fifty-eight out of 770 analyzed genes showed a significantly altered expression signature in COVID-19 compared to controls in a time-dependent manner. The entire study group showed an increased expression of Bone Marrow Stromal Cell Antigen 2 (BST2) and interleukin-1 receptor 1 (IL1R1), independent of hospitalization time. In the early group, there was increased activity of inflammation-related genes and pathways, while fibrosis-related genes (particularly PDGFRB) and pathways dominated in the late group. Conclusion(s): After the first week of hospitalization, there is a shift from pro-inflammatory to fibrogenic activity in severe COVID-19. IL1R1 and PDGFRB may serve as potential therapeutic targets in future studies.

4.
Nephrology Dialysis Transplantation ; 37(SUPPL 3):i30, 2022.
Article in English | EMBASE | ID: covidwho-1915659

ABSTRACT

BACKGROUND AND AIMS: Autopsies are an invaluable tool in medicine for studying the pathophysiology of diseases, including kidney diseases and causes of death. To facilitate multicenter autopsy-based studies and to provide a single point of contact for data analysis and reporting, the German COVID-19 Autopsy Registry (DeRegCOVID) was launched in April 2020 to uncover effects on pulmonary (micro)vasculature, systemic viral spread including the kidneys or interaction with the immune system. METHOD: The electronic registry uses a web-based electronic data collection system. Participation is voluntary and biomaterial remains at each site (decentralized biobanking). As of October 2021, the registry included N = 1129 autopsy cases with 69 271 individual data points containing information on 18 674 available biospecimens, including kidneys as part of the standard sampling protocol, collected at 29 German sites. RESULTS: In the N = 1095 eligible records, the male-to-female ratio was 1-8:1, with peaks at 65-69 and 80-84 years in men and >85 years in women. Analysis of the chain of events leading directly to death showed that in 86% of autopsy cases, COVID-19 was the actual cause of death, whereas in 14% of cases, COVID- 19 was a concomitant disease. The most common immediate cause of death was diffuse alveolar injury/acute respiratory distress syndrome, followed by multiorgan failure, including the kidneys. The registry supports several scientific projects, informs the public and provides reports to federal health authorities, which led to a change in the German Infection Protection Act and facilitated autopsies during pandemics. CONCLUSION: A national autopsy registry can provide multicenter quantitative information on COVID-19 deaths at the national level to support medical research, policy decisions and public discussions. Previous and ongoing studies also showed the potential of autopsies for nephrology research.

5.
Journal of the American College of Cardiology ; 79(9):1823-1823, 2022.
Article in English | Web of Science | ID: covidwho-1849432
6.
Cell ; 185(3):493-+, 2022.
Article in English | Web of Science | ID: covidwho-1757189

ABSTRACT

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16(+) T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16(+) T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16(+) T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16(+) cytotoxic T cells. Proportions of activated CD16(+) T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

7.
Pathologe ; 42(2): 183-187, 2021 Mar.
Article in German | MEDLINE | ID: covidwho-1235727

ABSTRACT

Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV­2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV­2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.


Subject(s)
Acute Kidney Injury , COVID-19 , Humans , Kidney , RNA, Viral , SARS-CoV-2
8.
Pathologe ; 42(Suppl 1): 76-80, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1148872

ABSTRACT

Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV­2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV­2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.


Subject(s)
Acute Kidney Injury , COVID-19 , Humans , Kidney , RNA, Viral , SARS-CoV-2
9.
Pathologe ; 42(2): 147-148, 2021 03.
Article in German | MEDLINE | ID: covidwho-1118220

Subject(s)
COVID-19 , Humans , SARS-CoV-2
10.
Pathologe ; 41(4):430-430, 2020.
Article in German | Web of Science | ID: covidwho-1001215
11.
Nephrologe ; 16(1): 14-19, 2021.
Article in German | MEDLINE | ID: covidwho-986658

ABSTRACT

Apart from the pulmonary disease, acute kidney injury is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could also be detected in renal tissue. Patients with chronic kidney disease and on dialysis as well as kidney transplantation patients represent a particularly vulnerable population. The increasing number of patients infected with SARS-CoV­2 has aroused increased interest in the exact pathophysiology and morphology of kidney damage as well as the direct detection of the virus in the kidneys, which in contrast to the lungs is overall more difficult to perform. Meanwhile, data from several large autopsy and kidney biopsy studies are now available. While the detection of SARS-CoV­2 RNA in tissue leads to consistently reproducible results, the use of electron microscopy for visualization of the virus is critically discussed due to various artefacts. The exact and direct effects of SARS-CoV­2 on the kidneys are not yet known in detail and are currently the focus of intensive research.

12.
Pathologe ; 41(Suppl 2): 96-98, 2020 Dec.
Article in German | MEDLINE | ID: covidwho-971648

ABSTRACT

This paper briefly summarizes the late-breaking session "Pathology and COVID-19" that took place at the virtual congress of the German Society of Pathology on June 6, 2020. The lectures tackled a broad variety of aspects, including the German Registry for COVID-19 autopsies (DeRegCOVID), the detection methods of SARS-CoV­2 in pathological material, the typical lung findings in severe COVID-19 cases, the distinct (micro)vascular changes and the cardiac and gastrointestinal involvement in COVID-19. In summary, in this first scientific meeting in German pathology on the COVID-19 pandemic, it became clear that pathologists in Germany, Austria and Switzerland have reacted very quickly to the pandemic and have established an autopsy program that has led to medically highly relevant findings.


Subject(s)
COVID-19 , Pandemics , Austria , Germany , Humans , Lung , SARS-CoV-2 , Switzerland
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