Putrefaction in the pandemic: a comparative study of the frequency of advanced decomposition change in coronial autopsies since the start of the COVID-19 pandemic.

AIMS: The aim of this study is to evaluate whether there has been a significant change in the frequency of markedly decomposed bodies having coronial autopsies since the UK's first COVID-19 lockdown. METHODS: We compared coronial autopsies (n=263) performed by one pathologist at a central London mortuary in the 1 year before and after 23 March 2020 by analysing their autopsy reports and coronial documentation. RESULTS: We have shown that there has been a significant increase of 70.5% (p=0.001) in the frequency of markedly decomposed bodies having coronial autopsies since the first lockdown. This is associated with a 38% increase (p=0.0001) in the rate of those dying at home and a 52.4% decrease (p=0.00003) in the rate of those dying in hospital who go on to have a coronial autopsy in our facility. Our results suggest that the most significant factor behind the increased frequency in advanced decomposition change since the first lockdown is this increase in coronial autopsies for deaths at home relative to deaths in hospital. CONCLUSION: Our results support the idea that perimortem social isolation will lead to an increased frequency of advanced decomposition changes seen at autopsy. We suggest that it could be possible to use the frequency of advanced postmortem decomposition change in a population as a surrogate marker for social isolation in future studies. Our study also illustrates a changing environment where the increasing prevalence of postmortem decomposition changes could affect the accuracy of autopsy reports and the medicolegal consequences thereof.

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review.

BACKGROUND: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. OBJECTIVES: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. DATA SOURCES: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. STUDY ELIGIBILITY CRITERIA: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. PARTICIPANTS: Confirmed COVID-19 patients with post-mortem cardiovascular findings. INTERVENTIONS: None. METHODS: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). RESULTS: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). CONCLUSIONS: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.

Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes.

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID postmortem controls. SARS-CoV-2 anti-NP staining in the postmortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms with the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Coronial postmortem reports and indirect COVID-19 pandemic-related mortality.

AIMS: Widespread disruption of healthcare services and excess mortality not directly attributed to COVID-19 occurred between March and May 2020. We undertook the first UK multicentre study of coroners' autopsies before and during this period using postmortem reports. METHODS: We reviewed reports of non-forensic coroners' autopsies performed during the first COVID-19 lockdown (23 March to 8 May 2020), and the same period in 2018. Deaths were categorised as natural non-COVID-19, COVID-19-related, non-natural (suicide, drug and alcohol-related, traumatic, other). We provided opinion regarding whether delayed access to medical care or changes in behaviour due to lockdown were a potential factor in deaths. RESULTS: Seven centres covering nine coronial jurisdictions submitted a total of 1100 coroners' autopsies (498 in 2018, 602 in 2020). In only 54 autopsies was death attributed to COVID-19 (9%). We identified a significant increase in cases where delays in accessing medical care potentially contributed to death (10 in 2018, 44 in 2020). Lockdown was a contributing factor in a proportion of suicides (24%) and drug and alcohol-related deaths (12%). CONCLUSIONS: Postmortem reports have considerable utility in evaluating excess mortality due to healthcare and wider societal disruption during a pandemic. They provide information at an individual case level that is not available from assessment of death certification data. Detailed evaluation of coroners' autopsy reports, supported by appropriate regulatory oversight, is recommended to mitigate disruption and indirect causes of mortality in future pandemics. Maintaining access to healthcare, including substance misuse and mental health services, is an important consideration.

Histological findings of tracheal samples from COVID-19 positive critically ill mechanically ventilated patients.

OBJECTIVES: This study examines the histological findings of tracheal tissue samples obtained from COVID-19 positive mechanically ventilated patients, to assess the degree of tracheal inflammation/ulceration present. DESIGN AND PARTICIPANTS: Retrospective single-centre observational cohort study. All patients admitted to Adult Intensive Care Unit (AICU) with COVID-19 infection, requiring mechanical ventilation and surgical tracheostomy between 1 April and 1 May 2020, were included (Group 1). Tracheal windows excised at tracheostomy underwent histological analysis. Comparison was made with: tracheal windows from COVID-19 positive AICU ventilated patients admitted between 1 January and 1 March 2021 (Group 2); tracheal windows from COVID-19 negative AICU ventilated patients (Group 3); and, tracheal autopsy samples from COVID-19 positive patients that died without undergoing prolonged mechanical ventilation (Group 4). RESULTS: Group 1 demonstrated mild/moderate inflammation (tracheitis) in nearly all samples (15/16, 93.8%), with infrequent micro-ulceration (2/16, 12.5%). Group 2 demonstrated similar mild/moderate inflammation in all samples (17/17, 100%), with no ulceration. Histological findings of Groups 1 and 2 COVID-19 positive patients were similar to Group 3 COVID-19 negative patients, which demonstrated mild/moderate inflammation (5/5, 100%), with uncommon superficial erosion (1/5, 20%). Group 4 demonstrated mild chronic inflammation or no significant inflammation, with uncommon micro-ulceration (1/4, 25%). CONCLUSIONS: Severe tracheal inflammation was not demonstrated in mechanically ventilated COVID-19 positive patients at the level of the second/third tracheal rings, at the stage of disease patients underwent tracheostomy. Histological findings were similar between mechanically ventilated COVID-19 positive and negative patients. Tracheal ulceration may be a feature of early or severe COVID-19 disease.

The Australian Youth Cancer Service: Developing and Monitoring the Activity of Nationally Coordinated Adolescent and Young Adult Cancer Care.

Adolescents and young adults (aged 15-25 years) diagnosed with cancer have unique medical and psychosocial experiences and care needs, distinct from those of paediatric and older adult patients. Since 2011, the Australian Youth Cancer Services have provided developmentally appropriate, multidisciplinary and comprehensive care to these young patients, facilitated by national service coordination and activity data collection and monitoring. This paper reports on how the Youth Cancer Services have conceptualised and delivered quality youth cancer care in four priority areas: clinical trial participation, oncofertility, psychosocial care and survivorship. National activity data collected by the Youth Cancer Services between 2016-17 and 2019-20 are used to illustrate how service monitoring processes have facilitated improvements in coordination and accountability across multiple indicators of quality youth cancer care, including clinical trial participation, access to fertility information and preservation, psychosocial screening and care and the transition from active treatment to survivorship. Accounts of both service delivery and monitoring and evaluation processes within the Australian Youth Cancer Services provide an exemplar of how coordinated initiatives may be employed to deliver, monitor and improve quality cancer care for adolescents and young adults.

Emerging spectrum of COVID-19-related cardiopulmonary pathology in adults.

COVID-19 is currently a major cause of morbidity and mortality in adults throughout the world. Given the high infection rate, it is increasingly likely that histopathologists will encounter this disease during their practice. Although COVID-19 is increasingly recognized as a multi-system disease, the lungs and, to a lesser degree, the heart remain the major sites of pathology. This article aims to acquaint the general histopathologist with the main pathological findings in the lungs and heart of adults with COVID-19. It highlights the need for clinicopathological correlation with a discussion of the cardiopulmonary clinical features in COVID-19 and relates those to the pathological findings. In the lungs, diffuse alveolar damage is emphasized with its variety of morphological appearances over time. It concludes with a discussion of the main techniques available to identify the virus in fixed tissues and their potential limitations related specifically to the heart and lungs.

The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets.

SARS-CoV-2 entry requires sequential cleavage of the spike glycoprotein at the S1/S2 and the S2' cleavage sites to mediate membrane fusion. SARS-CoV-2 has a polybasic insertion (PRRAR) at the S1/S2 cleavage site that can be cleaved by furin. Using lentiviral pseudotypes and a cell-culture-adapted SARS-CoV-2 virus with an S1/S2 deletion, we show that the polybasic insertion endows SARS-CoV-2 with a selective advantage in lung cells and primary human airway epithelial cells, but impairs replication in Vero E6, a cell line used for passaging SARS-CoV-2. Using engineered spike variants and live virus competition assays and by measuring growth kinetics, we find that the selective advantage in lung and primary human airway epithelial cells depends on the expression of the cell surface protease TMPRSS2, which enables endosome-independent virus entry by a route that avoids antiviral IFITM proteins. SARS-CoV-2 virus lacking the S1/S2 furin cleavage site was shed to lower titres from infected ferrets and was not transmitted to cohoused sentinel animals, unlike wild-type virus. Analysis of 100,000 SARS-CoV-2 sequences derived from patients and 24 human postmortem tissues showed low frequencies of naturally occurring mutants that harbour deletions at the polybasic site. Taken together, our findings reveal that the furin cleavage site is an important determinant of SARS-CoV-2 transmission.

Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study.

BACKGROUND: Severe COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19. METHODS: In this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients. FINDINGS: The median age at death of our cohort of ten patients was 73 years (IQR 52-79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients. INTERPRETATION: Our series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19. FUNDING: Imperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.

Autopsy in suspected COVID-19 cases.

The severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) outbreak in Wuhan, China has now spread to many countries across the world including the UK with an increasing death toll. This will inevitably lead to an increase in the number of suspected coronavirus disease 2019 (COVID-19)-related deaths at autopsy. The Royal College of Pathologists has responded to this concern with the release of a briefing on autopsy practice relating to COVID-19. The following article is a summary and interpretation of these guidelines. It includes a description of hazard group 3 organisms, the category to which SARS-CoV-2 has been assigned, a brief description of what is currently known about the pathological and autopsy findings in COVID-19, a summary of the recommendations for conducting autopsies in suspected COVID-19 cases and the techniques for making the diagnosis at autopsy. It concludes by considering the clinicopathological correlation and notification of such cases.