Viable SARS-CoV-2 Omicron sub-variants isolated from autopsy tissues.

Introduction: Pulmonary and extrapulmonary manifestations have been described after infection with SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The virus is known to persist in multiple organs due to its tropism for several tissues. However, previous reports were unable to provide definitive information about whether the virus is viable and transmissible. It has been hypothesized that the persisting reservoirs of SARS-CoV-2 in tissues could be one of the multiple potentially overlapping causes of long COVID. Methods: In the present study, we investigated autopsy materials obtained from 21 cadaveric donors with documented first infection or reinfection at the time of death. The cases studied included recipients of different formulations of COVID-19 vaccines. The aim was to find the presence of SARS-CoV-2 in the lungs, heart, liver, kidneys, and intestines. We used two technical approaches: the detection and quantification of viral genomic RNA using RT-qPCR, and virus infectivity using permissive in vitro Vero E6 culture. Results: All tissues analyzed showed the presence of SARS-CoV-2 genomic RNA but at dissimilar levels ranging from 1.01 × 102 copies/mL to 1.14 × 108 copies/mL, even among those cases who had been COVID-19 vaccinated. Importantly, different amounts of replication-competent virus were detected in the culture media from the studied tissues. The highest viral load were measured in the lung (≈1.4 × 106 copies/mL) and heart (≈1.9 × 106 copies/mL) samples. Additionally, based on partial Spike gene sequences, SARS-CoV-2 characterization revealed the presence of multiple Omicron sub-variants exhibiting a high level of nucleotide and amino acid identity among them. Discussion: These findings highlight that SARS-CoV-2 can spread to multiple tissue locations such as the lungs, heart, liver, kidneys, and intestines, both after primary infection and after reinfections with the Omicron variant, contributing to extending knowledge about the pathogenesis of acute infection and understanding the sequelae of clinical manifestations that are observed during post-acute COVID-19.

Undiagnosed pulmonary TB and COVID in adults dying at home in a high TB burden setting, before and during pandemic COVID-19: an autopsy study.

BACKGROUND: Missing or undiagnosed patients with TB or COVID-19 are of concern. Identifying both infections in patients with no diagnosis prior to death contributes to understanding burdens of disease. To confirm reports of global reduction in TB incidence a 2012 autopsy study of adults dying at home of natural causes, in a high TB burden setting was repeated, including SARS-CoV-2 assessments after the first COVID-19 surge in South Africa. METHODS: Adult decedents who died at home with insufficient information to determine cause of death, no recent hospitalisation, and no current antemortem TB or COVID-19 diagnosis were identified between March 2019 and October 2020 with a 4 month halt during lockdown. A standardised verbal autopsy followed by minimally-invasive needle autopsy (MIA) was performed. Biopsies were taken for histopathology from liver, bilateral brain and lung; bronchoalveolar lavage was collected for Xpert (MTB/RIF) and mycobacterial culture, and blood for HIV polymerase chain reaction (PCR) testing. After the start of the COVID-19 pandemic, a nasopharyngeal swab and lung tissue were subjected to SARS-CoV-2 PCR testing. RESULTS: Sixty-six MIA were completed, 25 men and 41 women, overall median age 60 years. 68.2% had antemortem respiratory symptoms and 30.3% were people with HIV (PWH). Overall, TB was diagnosed in 11/66 (16.7%) and 14/41 (34.1%) in the COVID-19 pandemic were SARS-CoV-2 positive. CONCLUSION: Undiagnosed TB in adults dying at home has apparently decreased but remains unacceptably high. Forty percent of decedents had undiagnosed COVID-19 suggest estimates of excess deaths may underestimate the impact of SARS-CoV-2 on mortality.

Doing More with Fewer: Optimizing Value with Limited Numbers of Autopsies

The value of autopsy is best demonstrated when the procedure is competently practiced in an appropriate clinical setting. Autopsy performance is expectedly restricted when a death raises certain forensic, religious, legal, or safety concerns. Additionally, limiting the scope of postmortem examinations to deaths that fulfill various clinical indications for the procedure will be important moving forward. This is especially true as institutions that finance autopsy services face uncertain and likely difficult financial conditions in the wake of the coronavirus disease 2019 pandemic. Autopsy pathologists should actively engage with clinicians in promoting responsible autopsy practice and delivering quality postmortem care. Using a problem-oriented autopsy record, thoughtfully evaluating postmortem histology, and purposefully reporting autopsy findings can help pathologists provide valuable data to autopsy's various stakeholders. Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Special Isue: Virtual anatomy, histology and embryology in research and education. (Special Isue: Virtual anatomy, histology and embryology in research and education.)

This issue contains 13 articles on the use of virtual anatomy, histology and embryology in research and education;digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications;an international collaborative approach to learning histology using a virtual microscope;delivery anatomy kits to help keep practical veterinary classes during the COVID-19 pandemic;how virtual animal anatomy facilitated a successful transition to online instruction and supported student learning during the coronavirus pandemic;using videos in active learning in veterinary anatomy;dissection videos as a virtual veterinary anatomy peer learning tool at the University of Tehran during the COVID-19 pandemic;a new virtual platform for teaching comparative animal neuroanatomy based on metameric slices of the central nervous system;application of student remote and distance research in neuroanatomy by mapping Dscaml1 expression with a LacZ gene trap in mouse brain;implementing a multi-colour genetic marker analysis technique for embryology education;impact of COVID-19 on student attainment and pedagogical needs when undertaking independent scientific research;extended reality veterinary medicine case studies for diagnostic veterinary imaging instruction and assessing student perceptions and examination performance and students' performance in teaching neuroanatomy using traditional and technology-based methods. 16 proceedings from the Trans-European Pedagogic Anatomy Research Group (TEPARG) Hybrid Meeting entitled "Hybrid Anatomy Education: Barriers and Enablers for Students and Educators" held in Barcelona, Spain, during 5 March 2022, are also included.

SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature.

INTRODUCTION: COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples. MATERIAL AND METHODS: We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022. RESULTS: In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples. CONCLUSION: This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature.

Alcohol use trends in Dallas County during the COVID-19 pandemic

Alcohol (ethanol) is the most widely detected drug in forensic toxicology casework and an increase in consumption of alcohol was reported during the COVID-19 pandemic. The increase in consumption could be attributed to rising stress levels and social isolation. To determine whether the pandemic had an impact on ethanol positivity and concentrations in cases analyzed by the Dallas County Southwestern Institute of Forensic Sciences, blood ethanol results were evaluated from January 1, 2019, through December 31, 2021. This time frame captured ethanol prevalence and concentrations before, during, and immediately following the pandemic for comparison. The average ethanol concentration in postmortem casework over the three years for each quarter ranged from 0.116 g/100 mL to 0.142 g/100 mL while the average concentration in driving while intoxicated (DWI) was higher, ranging from 0.173 g/100 mL to 0.188 g/100 mL. The ethanol positivity rate for postmortem casework remained relatively the same at approximately 20% during the time frame, while there was a decrease in ethanol positivity rate for DWI casework during the pandemic in April - June (Q2) 2020. However, the positivity rate returned to pre-pandemic levels by the end of 2020. Despite the self-reported surveys of increased alcohol consumption during the pandemic, a corresponding increase in average ethanol concentrations was not observed in Dallas County and the surrounding area.Copyright © 2023

TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.

High titers of infectious SARS-CoV-2 in corpses of patients with COVID-19.

OBJECTIVES: The prolonged presence of infectious SARS-CoV-2 in deceased patients with COVID-19 has been reported. However, infectious virus titers have not been determined. Such information is important for public health, death investigation, and handling corpses. The aim of this study was to assess the level of SARS-CoV-2 infectivity in the corpses of patients with COVID-19. METHODS: We collected 11 nasopharyngeal swabs and 19 lung tissue specimens from 11 autopsy cases with COVID-19 in 2021. We then investigated the viral genomic copy number by real-time reverse transcription-polymerase chain reaction and infectious titers by cell culture and virus isolation. RESULTS: Infectious virus was present in six of 11 (55%) cases, four of 11 (36%) nasopharyngeal swabs, and nine of 19 (47%) lung specimens. The virus titers ranged from 6.00E + 01 plaque-forming units/ml to 2.09E + 06 plaque-forming units/g. In all cases in which an infectious virus was found, the time from death to discovery was within 1 day and the longest postmortem interval was 13 days. CONCLUSION: The corpses of patients with COVID-19 may have high titers of infectious virus after a long postmortem interval (up to 13 days). Therefore, appropriate infection control measures must be taken when handling corpses.

Differences in interleukin-6 and interleukin-17 expression in COVID-19 post-mortem lung tissue biopsy compared with noncovid- 19

Background: COVID-19 has spread rapidly around the world. It is necessary to study lung tissue of postmortem COVID19 patients to determine the molecular alteration particularly the role of IL-6 and IL-17 in causing fatality. Background: This study aims to determine the differences in the expressions of IL-6 and IL-17 in lung tissue of post-mortem COVID-19 patients compared to non-COVID-19 patients. This study also aimed to analyze the correlation between the expressions of IL-6 and IL-17 in lung tissue of post-mortem COVID-19 patients. Methods: This research is an observational analytic study with crosssectional approach. The samples were 15 paraffin blocks of post-mortem lung tissue biopsy of COVID-19 patients, and 15 paraffin blocks of inflammatory lung tissue biopsy or surgery of non-COVID-19 patients. IL-6 and IL-17 expressions were evaluated by immunohistochemical procedure. Result: There was a significant difference in the expression of IL-6 in the COVID-19 group and the non-COVID-19 group with a p-value = 0.001 (p < 0.05). There was a significant difference in the expression of IL-17 in the COVID-19 group and the non-COVID-19 group with p-value = 0.001 (p < 0.05). There was a significant correlation between the expressions of IL-6 and IL-17 in the COVID-19 group, with the Spearman coefficient value (rs) of 0.548 with p = 0.034 (p < 0.05). Conclusion: There are differences in the expression of IL-6 and IL-17 between COVID-19 and non-COVID-19 lung tissue. There is a significant correlation between the expressions of IL-6 and IL-17 in post-mortem lung tissue of COVID-19 patients.

CLINICAL AND MORPHOLOGICAL ANALYSIS OF PULMONARY ASPERGILLOSIS COINFECTION IN COVID-19.

The article provided the information about the results of clinical-morphological analysis of the practical observation with pulmonary aspergillosis associated with COVID-19 and undiagnosed when the patient was alive. The pulmonary aspergillosis associated with COVID-19 is one of the widespread complications. However, in numerous cases, the pulmonary aspergillosis associated with COVID-19 is not diagnosed due to its unclear signs and lack of information about it. An infiltrate with signs of destruction was noted during X-ray examination of the lower part of the right lung of the observed patient. It was evaluated as destructive pneumonia associated with bacterial infection. However, despite the patient had type II diabetes, no additional examination methods were applied to exclude aspergillosis. Disruption of the protective properties of the bronchial epithelium and the effect of oseltamivir type drugs may also contribute to the entry of aspergillus fungi into the lung tissue. According to the authors, during the development of diagnosis, treatment and prevention strategy of COVID-19in the patients with pulmonary aspergillosis it is important to study the interaction of these diseases.Copyright © 2022 Authors. All rights reserved.

A case of fatal acute necrotising encephalopathy associated with probable SARS-CoV-2

Introduction. Clinical studies during the epidemic of a new coronavirus infection caused by the SARS-CoV-2 virus confirm not only neurotropic damage to the central nervous system, but also complex immune-mediated neurological complications of COVID 19, one of which is acute necrotizing encephalopathy. Purpose of the study. Presentation of a clinical case of acute fatal necrotizing encephalopathy resulting from a severe respiratory infection probably caused by the SARS-CoV-2 virus. Research methods. Retrospective analysis of the medical history, interpretation of clinical and laboratory data, neuroimaging studies and autopsy results in a 22-year-old patient with a fatal neurological complication of a respiratory infection that occurs with bilateral polysegmental interstitial pneumonia. Conclusions. Characteristic ground-glass lung changes suggested a new coronavirus infection caused by the SARS-CoV-2 virus, despite a negative PCR result for virus RNA in a nasopharyngeal and cerebrospinal fluid swab. The rapid increase in focal and cerebral neurological symptoms, diffuse changes and edema of the brain substance according to CT scan and subsequently according to the results of autopsy, signs of systemic inflammation and changes in the coagulating blood system confirmed the changes characteristic of the "cytokine storm" and DIC syndrome developing against the background of systemic endothelitis in COVID 19.

Postmortem Histopathologic Findings and SARS-CoV-2 Detection in Autopsy Kidneys of Patients With COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to investigate the prevalence of postmortem kidney histopathologic features of patients with coronavirus disease 2019 (COVID-19) in addition to the rate of renal tropism in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We searched Web of Science, PubMed, Embase, and Scopus up to September 2022 to identify eligible studies. A random-effects model was used to estimate the pooled prevalence. Cochran Q test and Higgins I2 were used to assess evidence of heterogeneity. RESULTS: In total, 39 studies were included in the systematic review. The meta-analysis included 35 studies consisting of a total of 954 patients, with an average age of 67.1 years. The pooled prevalence of acute tubular injury (ATI)-related changes was the predominant finding (85% [95% confidence interval, 71%-95%]), followed by arteriosclerosis (80%), vascular congestion (66%), and glomerulosclerosis (40%). Endotheliitis (7%), fibrin microthrombi (12%), focal segmental glomerulosclerosis (1%), and calcium crystal deposits (1%) were seen in a smaller number of autopsies. The overall average rate of virus detection was 47.79% in the pooled data of 21 studies (272 samples). CONCLUSIONS: The main finding-ATI-correlated to clinical COVID-19-associated acute kidney injury. The presence of SARS-CoV-2 in kidney samples in addition to vascular lesions in kidneys can be linked to direct kidney invasion by the virus.

Causes of death and post-mortem testing for SARS-CoV-2 in a tertiary hospital during the COVID-19 pandemic in Ghana.

Background: Causes of death during the coronavirus disease 2019 (COVID-19) pandemic ranhttp://crossmark.crossref.org/dialog/?doi=10.4102/ajlm.v11i1.1766=pdf&date_stamp=2022-11-23ge from direct consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to deaths unrelated to SARS-CoV-2. Another feature of the pandemic is the post-mortem testing for SARS-CoV-2. Understanding these aspects of COVID-19 are essential in planning and limiting the impact of SARS-CoV-2 virus on healthcare systems. Objective: This study investigated the underlying causes of death and the presence of SARS-CoV-2 in bodies received at the 37 Military Hospital, Accra, Ghana, during the COVID-19 pandemic. Methods: The study was conducted from 4-27 May 2020. Deceased patients that met the inclusion criteria were prospectively selected during the expanded surveillance period for SARS-CoV-2 testing, autopsy and determination of underlying and immediate cause of death. Results: A total of 161 deceased patients were analysed with 53 autopsies. The overall positive test rate for SARS-CoV-2 was 14.9% (24/161 patients), with a positive rate of 5.0% (8/161 patients) for nasopharyngeal samples and 30.2% (16/161 patients) for bronchopulmonary samples. The underlying causes of death were not related to SARS-CoV-2 infection in 85.1% (137/161) of patients, SARS-CoV-2-associated 12.4% (20/161) and SARS-CoV-2-induced in 2.5% (4/161). Cardiovascular complications formed the most common cause of death in patients with or without SARS-CoV-2. Conclusion: There was a high positive rate of SARS-CoV-2 in post-mortem cases. However, most deaths were not caused by SARS-CoV-2 but by cardiovascular complications. The high rate of bronchopulmonary positive results for SARS-CoV-2 requires that autopsies be done in suspicious cases with negative nasopharyngeal sampling.

SARS-CoV-2 persistence and infectivity in COVID-19 corpses: a systematic review.

The persistence and infectivity of SARS-CoV-2 in different postmortem COVID-19 specimens remain unclear despite numerous published studies. This information is essential to improve corpses management related to clinical biosafety and viral transmission in medical staff and the public community. We aim to understand SARS-CoV-2 persistence and infectivity in COVID-19 corpses. We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocols. A systematic literature search was performed in PubMed, Science Direct Scopus, and Google Scholar databases using specific keywords. We critically reviewed the collected studies and selected the articles that met the criteria. We included 33 scientific papers that involved 491 COVID-19 corpses. The persistence rate and maximum postmortem interval (PMI) range of the SARS-CoV-2 findings were reported in the lungs (138/155, 89.0%; 4 months), followed by the vitreous humor (7/37, 18.9%; 3 months), nasopharynx/oropharynx (156/248, 62.9%; 41 days), abdominal organs (67/110, 60.9%; 17 days), skin (14/24, 58.3%; 17 days), brain (14/31, 45.2%; 17 days), bone marrow (2/2, 100%; 12 days), heart (31/69, 44.9%; 6 days), muscle tissues (9/83, 10.8%; 6 days), trachea (9/20, 45.0%; 5 days), and perioral tissues (21/24, 87.5%; 3.5 days). SARS-CoV-2 infectivity rates in viral culture studies were detected in the lungs (9/15, 60%), trachea (2/4, 50%), oropharynx (1/4, 25%), and perioral (1/4, 25%) at a maximum PMI range of 17 days. The SARS-CoV-2 persists in the human body months after death and should be infectious for weeks. This data should be helpful for postmortem COVID-19 management and viral transmission preventive strategy.

Postmortem lung and heart examination of COVID-19 patients in a case series from Jordan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic for more than 2 years. Autopsy examination is an invaluable tool to understand the pathogenesis of emerging infections and their consequent mortalities. The aim of the current study was to present the lung and heart pathological findings of COVID-19-positive autopsies performed in Jordan. METHODS: The study involved medicolegal cases, where the cause of death was unclear and autopsy examination was mandated by law. We included the clinical and pathologic findings of routine gross and microscopic examination of cases that were positive for COVID-19 at time of death. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed through molecular detection by real-time polymerase chain reaction, serologic testing for IgM and electron microscope examination of lung samples. RESULTS: Seventeen autopsies were included, with male predominance (76.5%), Jordanians (70.6%), and 50 years as the mean age at time of death. Nine out of 16 cases (56.3%) had co-morbidities, with one case lacking such data. Histologic examination of lung tissue revealed diffuse alveolar damage in 13/17 cases (76.5%), and pulmonary microthrombi in 8/17 cases (47.1%). Microscopic cardiac findings were scarcely detected. Two patients died as a direct result of acute cardiac disease with limited pulmonary findings. CONCLUSIONS: The detection of SARS-CoV-2 in postmortem examination can be an incidental or contributory finding which highlights the value of autopsy examination to determine the exact cause of death in controversial cases.

[Simulation in the elective subject forensic medicine in the third section of the medical examination]. / Simulation im Wahlfach Rechtsmedizin im Dritten Abschnitt der Ärztlichen Prüfung.

During the COVID-19 pandemic the third section of the medical examination could be performed on simulation patients and simulators. Their use is also beneficial in forensic medicine, as a higher level of standardization and comparability of examination performance is achieved, and the use of real corpses is often not justifiable for medicolegal reasons. This case reports on the advantages and disadvantages of a simulation in the state examination in which a death certificate was to be completely filled out on the basis of an external postmortem examination on the simulator and an external anamnesis.

Leveraging Serosurveillance and Postmortem Surveillance to Quantify the Impact of COVID-19 in Africa.

BACKGROUND: The COVID-19 pandemic has had a devastating impact on global health, the magnitude of which appears to differ intercontinentally: for example, reports suggest 271,900 per million people have been infected in Europe versus 8,800 per million people in Africa. While Africa is the second largest continent by population, its reported COVID-19 cases comprise <3% of global cases. Although social, environmental, and environmental explanations have been proposed to clarify this discrepancy, systematic infection underascertainment may be equally responsible. METHODS: We seek to quantify magnitudes of underascertainment in COVID-19's cumulative incidence in Africa. Using serosurveillance and postmortem surveillance, we constructed multiplicative factors estimating ratios of true infections to reported cases in Africa since March 2020. RESULTS: Multiplicative factors derived from serology data (subset of 12 nations) suggested a range of COVID-19 reporting rates, from 1 in 2 infections reported in Cape Verde (July 2020) to 1 in 3,795 infections reported in Malawi (June 2020). A similar set of multiplicative factors for all nations derived from postmortem data points toward the same conclusion: reported COVID-19 cases are unrepresentative of true infections, suggesting a key reason for low case burden in many African nations is significant underdetection and underreporting. CONCLUSIONS: While estimating COVID-19's exact burden is challenging, the multiplicative factors we present furnish incidence estimates reflecting likely-to-worst-case ranges of infection. Our results stress the need for expansive surveillance to allocate resources in areas experiencing discrepancies between reported cases, projected infections, and deaths.

Design and Development of Virtual Autopsy System for Teaching Medical Undergraduates

In recent decades, the utilization of autopsies as a teaching tool in undergraduate medical education is facing many challenges due to the nature of the medico legal issues. Aside from that, school closures and remote or hybrid learning environments manifested during Covid-19 pandemic have created more challenges for educators. Students are missing out the autopsy-based teaching, which provide various advantages. Moreover, it is difficult to assess students in ways that encourage and empower them to progress. Fortunately, the technology has the potential to provide a virtual museum with an interactive cadaver of several case studies, each with its own history and narrative beside, quizzes and assessments that give educational reasoning, analyze and track the user's learning. The objective of this research is to establish a virtual system for teaching the basis of Forensic medicine to medical students. The system is developed as a web based system, moreover this research uses Agile development approach as the methodology for this system development, the platform is developed to provide a single platform for material, assessment and feedback. Therefore, including 3 stages of the teaching and learning process, the system include scope for educators and learners as well. © 2022 IEEE.

Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19.

SARS-CoV-2 infection is clinically heterogeneous, ranging from asymptomatic to deadly. A few patients with COVID-19 appear to recover from acute viral infection but nevertheless progress in their disease and eventually die, despite persistent negativity at molecular tests for SARS-CoV-2 RNA. Here, we performed post-mortem analyses in 27 consecutive patients who had apparently recovered from COVID-19 but had progressively worsened in their clinical conditions despite repeated viral negativity in nasopharyngeal swabs or bronchioalveolar lavage for 11-300 consecutive days (average: 105.5 days). Three of these patients remained PCR-negative for over 9 months. Post-mortem analysis revealed evidence of diffuse or focal interstitial pneumonia in 23/27 (81%) patients, accompanied by extensive fibrotic substitution in 13 cases (47%). Despite apparent virological remission, lung pathology was similar to that observed in acute COVID-19 individuals, including micro- and macro-vascular thrombosis (67% of cases), vasculitis (24%), squamous metaplasia of the respiratory epithelium (30%), frequent cytological abnormalities and syncytia (67%), and the presence of dysmorphic features in the bronchial cartilage (44%). Consistent with molecular test negativity, SARS-CoV-2 antigens were not detected in the respiratory epithelium. In contrast, antibodies against both spike and nucleocapsid revealed the frequent (70%) infection of bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. In a few patients (19%), we also detected positivity in vascular pericytes and endothelial cells. Quantitative RT-PCR amplification in tissue lysates confirmed the presence of viral RNA. Together, these findings indicate that SARS-CoV-2 infection can persist significantly longer than suggested by standard PCR-negative tests, with specific infection of specific cell types in the lung. Whether these persistently infected cells also play a pathogenic role in long COVID remains to be addressed. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Autopsy Findings and Inflammatory Markers in SARS-CoV-2: A Single-Center Experience.

Purpose: The systemic inflammatory response related to COVID-19 can be easily investigated in living patients. Unfortunately, not every biomarker is suitable for postmortem analysis since several factors may interfere. The aim of this study was to summarize key histopathological findings within each organ system due to COVID-19 and to assess if serological inexpensive and widely available biomarkers such as CRP, IL-6, fibrinogen and d-Dimers, associated with adverse outcomes in COVID-19, can be implemented in a post-mortem assessment. Patients and Methods: A total of 60 subjects divided in 2 groups were included. All subjects died outside a hospital setting and therefore did not receive specific or symptomatic therapies that could have modulated the inflammatory response. The first group included 45 subjects in which mandatory autopsy was performed in order to establish the cause of death and macroscopic examination of the lungs was highly suggestive of SARS-CoV-2 infection. As controls (Group 2), 20 subjects who died from polytrauma in high velocity car accidents and suicide were selected. Bronchial fluids collected during the autopsy procedure were used for the RT-PCR diagnosis of SARS-CoV-2 and serum samples were sent for analysis of IL-6, CRP, d-Dimers and fibrinogen. Results: Compared with the control group, the subjects of the COVID-19 group were older (59±19.5 vs.38±19.15 years, p=0.0002) and had more underlying comorbidities such as hypertension (60% vs 35%, p=0.06) or were overweight (53.3% vs 30%, p=0.08). The levels of CRP, IL-6, fibrinogen and d-Dimers in postmortem plasma samples were significantly higher in COVID-19 subjects than in control group (p< 0.0001). Moreover, the level of IL-6 was significantly higher in overweight patients (r=0.52, P<0.001). In all COVID-19 subjects, the histological examination revealed features corresponding to the exudative and/or proliferative phases of diffuse alveolar damage. Large pulmonary emboli were observed in 7 cases. Gross cardiac enlargement with left ventricular hypertrophy was observed in 19 cases. The most frequent pathological finding of the central nervous system was acute/early-subacute infarction. Conclusion: Due to the complexity of the inflammatory response, we postulate that a combination of biomarkers, rather than a single laboratory parameter, might be more effective in obtaining a reliable postmortem COVID-19 diagnosis.