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Invasive mould disease in fatal COVID-19: a systematic review of autopsies.

ABSTRACT: Invasive mould disease (IMD) might affect up to a third of critically ill patients with COVID-19. COVID-19-associated pulmonary aspergillosis (CAPA) is typically diagnosed on the basis of a combination of non-specific clinical, radiographical, and mycological findings, but whether most cases represent invasive disease is unresolved. We systematically reviewed autopsy series of three or more decedents with COVID-19 for evidence of IMD. We searched PubMed, Web of Science, OVID (Embase), and medRxiv for studies in English or French published from Jan 1, 2019, to Sept 26, 2020. We identified 1070 references, of which 50 studies met the criteria. These studies described autopsies from 677 decedents, with individual-level data for 443 decedents. The median age was 70·0 years (IQR 57·0-79·0). Of decedents with individual-level data, 133 (30%) had diabetes, 97 (22%) had pre-existing lung disease, and 27 (6%) had immunocompromising conditions. Of 548 decedents with such data, 320 (58%) received invasive mechanical ventilation; among 140 decedents for whom this was known, ventilation was for a median of 9·0 days (IQR 5·0-20·0). Treatment included immunomodulation in 60 decedents and antifungals in 50 decedents. Autopsy-proven IMD occurred in 11 (2%) of 677 decedents, including eight CAPA, two unspecified IMD, and one disseminated mucormycosis. Among 320 decedents who received mechanical ventilation, six (2%) had IMD. We conclude that IMD, including CAPA, is an uncommon autopsy finding in COVID-19.

SUBMITTER: Kula BE

PROVIDER: S-EPMC8221729 | biostudies-literature |

REPOSITORIES: biostudies-literature

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COVID-19 and the Heart: A Systematic Review of Cardiac Autopsies.

Project description:Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated cardiac injury has been postulated secondary to several mechanisms. While tissue diagnosis is limited during the acute illness, postmortem studies can help boost our understanding and guide management. Objective: To report the cardiac tissue autopsy findings in coronavirus disease 2019 (COVID-19) decedents. Evidence Review: Articles published in PubMed and Embase reporting postmortem cardiac pathology of COVID-19 decedents till September 2020. We included adult studies excluding preprints. The Joanna Briggs Institute Critical Appraisal Checklist for Case Reports was used to assess quality. We extracted gross and histology data as well as the incidence of myocarditis, cardiac ischemia, thrombosis, and dilatation. We also looked at the reported cause of death (PROSPERO registration CRD42020190898). Findings: Forty-one relevant studies identified including 316 cases. The deceased were mostly male (62%) and elderly (median age, 75; range, 22-97 years). The most common comorbidities were hypertension (48%) and coronary artery disease (33%). Cardiac pathologies contributed to the death of 15 cases. Besides chronic cardiac pathologies, postmortem examination demonstrated cardiac dilatation (20%), acute ischemia (8%), intracardiac thrombi (2.5%), pericardial effusion (2.5%), and myocarditis (1.5%). SARS-CoV-2 was detected within the myocardium of 47% of studied hearts. Conclusions and Relevance: SARS-CoV-2 can invade the heart, but a minority of cases were found to have myocarditis. Cardiac dilatation, ischemia, mural, and microthrombi were the most frequent findings. The systematic review was limited by the small number of cases and the quality of the studies, and there is a need to standardize the cardiac postmortem protocols.

| S-EPMC7876291 | biostudies-literature

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-20 | GSE182299 | GEO

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [scRNA-Seq]

Project description:Our work illustrates how high-resolution molecular and spatial profiling of COVID-19 patient tissues collected during rapid autopsies can serve as a hypothesisgenerating tool to identify key mediators driving the pathophysiology of COVID-19 for diagnostic and therapeutic target testing. Here we employ bulk RNA sequencing to identify key regulators of COVID-19 and list specific mediators for further study as potential diagnostic and therapeutic targets. We use single-nuclei RNA sequencing to highlight the diversity and heterogeneity of coronavirus receptors within the brain, suggesting that it will be critical to expand the focus from ACE2 to include other receptors, such as BSG and ANPEP, and we perform digital spatial profiling of lung and lymph node tissue to compare two patients with different clinical courses and symptomatology.

2021-08-20 | GSE182298 | GEO

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [RNA-Seq]

2021-08-20 | GSE182297 | GEO

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [Digital Spatial Profiling data]

2021-09-03 | GSE183356 | GEO

Fatal COVID-19 pulmonary disease involves ferroptosis.

Project description:<p>SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.</p>

2024-07-11 | MTBLS3107 | MetaboLights

[Practical aspects of COVID-19 autopsies].

Project description:BackgroundThe COVID-19 pandemic represents a so far unknown challenge for the medical community. Autopsies are important for studying this disease, but their safety was challenged at the beginning of the pandemic.ObjectivesTo determine whether COVID-19 autopsies can be performed under existing legal conditions and which safety standards are required.Materials and methodsThe autopsy procedure undertaken in five institutions in Germany, Austria, and Switzerland is detailed with respect to legal and safety standards.ResultsIn all institutions the autopsies were performed in technically feasible rooms. The personal equipment consisted of functional clothing including a disposable gown and apron, a surgical cap, eye protection, FFP?3 masks, and two pairs of gloves. In four institutions, complete autopsies were performed; in one institution the ultrasound-guided biopsy within the postmortal imaging and biopsy program. The latter does not allow the appreciation of gross organ pathology; however, it is able to retrieve standardized biopsies for diagnostic and research purposes. Several scientific articles in highly ranked journals resulted from these autopsies and allowed deep insights into organ damage and conclusions to better understand the pathomechanisms. Viral RNA was frequently detectable in the COVID-19 deceased, but the issue of infectivity remains unresolved and it is questionable if Ct values are greater than 30.ConclusionsWith appropriate safeguards, autopsies of people who have died from COVID-19 can be performed safely and are highly relevant to medical research.

| S-EPMC7903213 | biostudies-literature

Molecular Profiling of Coronavirus Disease 2019 (COVID-19) Autopsies Uncovers Novel Disease Mechanisms.

Project description:Current understanding of coronavirus disease 2019 (COVID-19) pathophysiology is limited by disease heterogeneity, complexity, and a paucity of studies assessing patient tissues with advanced molecular tools. Rapid autopsy tissues were evaluated using multiscale RNA-sequencing methods (bulk, single-nuclei, and spatial RNA-sequencing next-generation sequencing) to provide unprecedented molecular resolution of COVID-19 induced damage. Comparison of infected/uninfected tissues revealed four major regulatory pathways. Effectors within these pathways could constitute novel therapeutic targets, including the complement receptor C3AR1, calcitonin receptor-like receptor, or decorin. Single-nuclei RNA sequencing of olfactory bulb and prefrontal cortex highlighted remarkable diversity of coronavirus receptors. Angiotensin-converting enzyme 2 was rarely expressed, whereas basigin showed diffuse expression, and alanyl aminopeptidase, membrane, was associated with vascular/mesenchymal cell types. Comparison of lung and lymph node tissues from patients with different symptoms (one died after a month-long hospitalization with multiorgan involvement, and the other died after a few days of respiratory symptoms) with digital spatial profiling resulted in distinct molecular phenotypes. Evaluation of COVID-19 rapid autopsy tissues with advanced molecular techniques can identify pathways and effectors, map diverse receptors at the single-cell level, and help dissect differences driving diverging clinical courses among individual patients. Extension of this approach to larger data sets will substantially advance the understanding of the mechanisms behind COVID-19 pathophysiology.

| S-EPMC8423774 | biostudies-literature

The use of non-invasive ventilation in COVID-19: A systematic review.

Project description:ObjectiveGuidelines from different regions on the use of non-invasive ventilation in COVID-19 have generally been inconsistent. The aim of this systematic review was to appraise the quality and availability of guidelines, and whether non-invasive ventilation in the early stages of the pandemic is of importance.Design and methodDatabases, including PubMed, Web of Science, and Cochrane Library, as well as websites of international organizations and gray literature, were searched up to June 23, 2020. The reference lists of eligible papers were also hand-searched.ResultsA total of 26 guidelines met the inclusion criteria. According to the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, the guidelines' methodological quality was low. Among six domains, Rigour of Development and Editorial Independence were of the lowest quality. Given the lack of evidence from randomized clinical trials and the great variation between different regions, recommendations for non-invasive ventilation have generated considerable debate regarding the early stages of COVID-19.ConclusionsImproving the methodological quality of the guidelines should be a goal with regard to future pandemics. Additionally, better-designed randomized clinical trials are needed to resolve contradictions regarding the impact of non-invasive ventilation.Prospero registration numberCRD42020198410.

| S-EPMC8008782 | biostudies-literature

Multi-organ proteomic landscape of COVID-19 autopsies.

Project description:The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.

| S-EPMC7794601 | biostudies-literature

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