What can autopsy say about COVID-19? A case series of 60 autopsies.

INTRODUCTION: Autopsies in SARS-CoV-2 infected cadavers are mainly performed to distinguish patients who died with SARS-CoV-2 infection from those who died of COVID-19. The aim of the current study is to assess the most frequent autopsy findings in patients who died of COVID-19 and to establish an association with clinical records. MATERIALS AND METHODS: 60 patients died between April 2020 and March 2021 after SARS-CoV-2 infection underwent a full autopsy performed at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome). Ante-mortem diagnosis of SARS-CoV-2 infection was microbiologically confirmed. RESULTS: 55 (92%) of cases had at least a comorbidity. At microscopic examination, 40 (67%) of the patients presented pulmonary intravascular coagulation with an inflammatory pattern. Pulmonary microangiopathy was a rare finding (n = 8; 13%). Myocardiosclerosis was the main heart finding (n = 44; 73%). Liver involvement with congestion and hypotrophy was found in 33 (55%) of cadavers. Renal tubular epithelial exfoliation (n = 12; 20%) and intravascular coagulation (n = 4; 7%) were frequent observations. During hospitalization 31% of patients (n = 19) developed acute kidney injury (AKI). CONCLUSIONS: Lungs and kidneys have been shown to play a pivotal role in COVID-19. The gradual worsening of renal function and AKI might be the result of the progressive collapse of cardiopulmonary system.

Liver injury associated with high value of D-dimer plasmatic level in COVID-19 patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19), has infected millions of people worldwide. Currently, the scientific community debates on the direct viral responsibility of liver damage or whether the observed changes are secondary manifestations of systemic inflammation triggered by COVID-19. The hepatic involvement is associated with worse clinical outcomes and higher risk of COVID-19 related morbidity and mortality. Furthermore, SARS-CoV-2 infection may predispose patients to thrombotic disease due to excessive inflammation, platelet activation, and endothelial dysfunction. METHODS: In this paper, we reported a cross-sectional analysis of five patients affected by a severe form of COVID-19, who died between April 11 and May 1, 2020. Each patient has been subjected to a medico-legal autopsy in which both gross and histological liver changes were evaluated, as well as the correlation with the related coagulation profile. RESULTS: In three cases of our cohort, the thromboembolism was recognized as cause of death. Furthermore, a significant statistical difference between D-dimer values at hospital admission and death among enrolled patients (p= 0.033), was evaluated. No patient has recorded a pre-existing liver disease. CONCLUSIONS: Our results support the evidence that hepatic damage in subjects with severe form of COVID-19 is related to the changes in coagulative and fibrinolytic pathways. Hence, the evaluation of D-dimer blood levels may be useful in clinical practice to predict the involvement of the liver and the prognosis of these patients. This data highlights the fundamental role of coagulation balance in subjects with advanced form of COVID-19.

Eosinophilic Infiltration of the Sino-Atrial Node in Sudden Cardiac Death Caused by Long QT Syndrome.

Sudden death is defined as the unexpected death of a healthy person that occurs within the first hour of the onset of symptoms or within 24 h of the victim being last seen alive. In some of these cases, rare deleterious variants of genes associated with inherited cardiac disorders can provide a highly probable explanation for the fatal event. We report the case of a 21-year-old obese woman who lost consciousness suddenly in a public place and was pronounced dead after hospital admission. Clinical autopsy showed an inconclusive gross examination, while in the histopathological analysis an eosinophilic inflammatory focus and interstitial fibrosis in the sino-atrial node were found. Molecular autopsy revealed an intronic variant in the KCNQ1 gene (c.683 + 5G > A), classified as likely pathogenic for long QT syndrome according to the guidelines provided by the American College of Medical Genetics and Genomics. Therefore, there were many anomalies that could have played a role in the causation of the sudden death, such as the extreme obesity, the cardiac anomalies and the KNCQ1 variant. This case depicts the difficult interpretation of rare cardiac structural abnormalities in subjects carrying rare variants responsible for inherited arrhythmic disorders and the challenge for the forensic pathologist to make causal inferences in the determinism of the unexpected decease.

Virtual autopsy in SARS-CoV-2 breakthrough infection: a case report

It is well documented that COVID-19 vaccines are effective tools for limiting the pandemic. Unfortunately, as is true for all vaccines, SARS-CoV-2 infection in vaccinated individuals is still possible. We present an autopsy case of SARS-CoV-2 infection after vaccination (“breakthrough infection”) in an elderly man with several comorbidities where post-mortem CT scan was performed. The death was histologically attributed to cardio-respiratory arrest due to ischemic heart failure related to superinfected COVID-19 pneumonia and pre-existing comorbidities. For the first time in the literature, PMCT imaging related to a fatal, autopsy case of breakthrough SARS-CoV-2 infection is reported. PMCT of the lungs, in accordance with histopathological results, showed few signs of COVID-19 pneumonia, large area of consolidation in the right lower lobe, interpreted as bronco-pneumonic focus, and hypostasis. These findings were well-correlated with the previously reported literature about both PMCT and clinical CT imaging of the lungs in non-vaccinated individuals with early COVID-19 pneumonia and about pulmonary clinical CT imaging in COVID-19 pneumonia in breakthrough SARS-COV-2 infections. Further studies are needed to cover the whole spectrum of PMCT lung imaging in fatal breakthrough SARS-CoV-2 infection, however, this case represent a first step for exploring this difficult challenge during SARS-CoV-2 pandemic using virtual autopsy.

Postmortem CT pulmonary findings in SARS-CoV-2-positive cases: correlation with lung histopathological findings and autopsy results.

INTRODUCTION/PURPOSE: Postmortem computed tomography (PMCT) is a valuable tool for analyzing the death of patients with SARS-CoV-2 infection. The purpose of this study was to investigate the correlation between PMCT lung findings in autopsy cadavers positive for SARS-CoV-2 infection and the severity of COVID-19 lung disease by histopathological analysis. MATERIALS AND METHODS: We reviewed chest PMCT findings, paying particular attention to the lung parenchyma, in 8 autopsy cases positive for SARS-CoV-2. Correlations between chest PMCT and histopathological findings were assessed. Clinical conditions and comorbidities were also recorded and discussed. The primary cause of death was finally considered. RESULTS: In 6/8 cases, pulmonary PMCT findings were massive consolidation (4/8) and bilateral diffuse mixed densities with a crazy-paving pattern (2/8). These cases showed severe pulmonary signs of COVID-19 at histopathological analysis. In the remaining 2/8 cases, pulmonary PMCT findings were scant antideclive ground-glass opacities in prevalent gradient densities attributed to hypostasis. In 4/8 cases with massive consolidations, important comorbidities were noted. In 6/8 cases with severe pulmonary histopathological signs of lung COVID-19, autopsy found that the cause of death was cardiorespiratory failure. In the remaining 2/8 cases, histopathological analysis revealed lung alterations due to edema and some signs of SARS-CoV-2 infection; the cause of death was not attributed to SARS-CoV-2 infection (Table 1). DISCUSSION AND CONCLUSION: Chest PMCT findings correlate with the severity of COVID-19 lung disease at histopathology examination. According to our results, there may also be a relationship between cause of death and PMCT findings in COVID-19, which must be critically analyzed considering clinical antemortem data.

SARS-CoV-2 viral load and replication in postmortem examinations.

We examined 29 autopsy cases (investigated between October 2020 and February 2021) whose postmortem swabs tested positive for SARS-CoV-2. Twenty-two of 29 cases died while hospitalized (H), while the remaining 7 cases were not hospitalized (NH). Since we included only cases in which the time since death was known (excluding unwitnessed NH deaths), the interval between death and postmortem swab(s) was registered, with a mean NH value of 5.50 days and a mean H value of 3.98 days. The mean age of NH was 65 years, while H were older (mean age: 73 years). Twenty-eight nasopharyngeal and 27 lungs postmortem swabs were obtained and real-time reverse transcriptase‒polymerase chain reaction assay for total and replicative SARS-CoV-2 RNA and mRNA detection was performed. Although the mean death-postmortem swabs interval was higher in NH than in H, the mean viral load of NH was higher than that of H (2.53 × 1011 copies/mL vs 9.31 × 108 copies/mL). In 13/29 cases (6 NH and 7 H), indicators of active replication were found. The relationship between the presence of replicative mRNA and death without hospitalization and that between the minimum cycle threshold value of SARS-CoV-2 RNA and the cycle threshold value of replicative SARS-CoV-2 mRNA were found to be statistically significant (with respective P values of 0.013 and 0.000). Therefore, especially in NH, full compliance with guidelines on biological safety in the autopsy room is essential, and no autopsy can be performed on infected cases in a structure that does not meet the established safety criteria.

SARS-CoV-2 Infection in Pregnancy: Clinical Signs, Placental Pathology, and Neonatal Outcome-Implications for Clinical Care.

Introduction: The current COVID-19 pandemic has been associated with high rates of mortality and significant morbidity. Both the risk of infection for pregnant women and the risk of vertical transmission have been evaluated, and the presence of the SARS-CoV-2 virus has been demonstrated both in the placenta and in the amniochorionic membranes. However, the actual effects of this pathogen on pregnancy and on placental morphology are still unclear. Objective: To describe histopathologic findings in the placentas of women with SARS-CoV-2 infection during pregnancy and their correlation with clinical signs and perinatal outcome. Methods: Placental tissues from pregnant women with SARS-CoV-2 infection delivering between March 2020 and February 2021 were analyzed. Results: One hundred six placentas from women with SARS-CoV-2 infection during pregnancy who delivered in Fondazione Policlinico A. Gemelli were examined. Most of them were asymptomatic. All neonates had available test results for SARS-CoV-2 and only one resulted positive. Placental tissues mainly showed signs of maternal vascular malperfusion and of placenta injury in terms of syncytial node increase (96.2%), villar agglutination (77.3%), neointimal hyperplasia (76.4%), excessive fibrin deposition (43.3%), and chorangiosis (35.8%). No significant differences in the frequency of the histopathological lesions were observed according to maternal symptoms. Conclusion: Looking to placental tissues from SARS-CoV-2 positive women at the screening performed close to delivery, placental injuries could be detected without any correlation with fetal and neonatal outcomes. We hypothesize that short latency between SARS-CoV-2 infection and delivery is the main reason for these observations.

COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.

Claimed medical malpractice in fatal SARS-CoV-2 infections: the importance of combining ante- and post-mortem radiological data and autopsy findings for correct forensic analysis

We present the case of an elderly woman who died from COVID-19 during the first wave of the pandemic. The physicians in charge of the patient were later accused of medical malpractice resulting in the death of the patient. The article reviews the comprehensive medico-legal investigations into this case that included an analysis of the medical history, clinical imaging, post-mortem imaging, autopsy, histopathology, and microbiology as well as an assessment of the medical knowledge regarding transmission of the SARS-CoV-2 virus and the management of COVID-19 at the time of the patient's death. The investigation resulted in a verdict of not guilty. This case highlights the value of clinical and post-mortem imaging as well as various challenges of medico-legal investigations of COVID-19 related deaths.

Analysis of the persistence time of the SARS-CoV-2 virus in the cadaver and the risk of passing infection to autopsy staff.

The activity of the SARS-CoV-2 virus has not yet been studied in a post-mortem setting. The absence of these data has led to the prohibition of exposure of infected corpses during burial procedures. Our aim was to assess the virus's persistence and the possibility of transmission in the post-mortem phase including autopsy staff. The sample group included 29 patients who were admitted to our Covid-19 Centre who died during hospitalisation and the autopsy staff. All the swabs were subjected to a one-step real-time reverse transcription polymerase chain reaction with cycle threshold (Ct) values. Swab collection was performed at 2 h, 4 h, 6 h, 12 h, over 24 since death. The following were the analysis of patients' swabs: 10 cases were positive 2 h after death; 10 cases positive 4 h after death; 9 cases were found positive 6 h after death; 7 cases positive 12 h after death; 9 cases remained positive 24 h after death. The swabs performed on all the forensic pathologist staff on duty who performed the autopsies were negative. The choice to avoid rituals and the display of corpses before and at the burial procedures given appears cautiously valid due to the persistence of the SARS-CoV-2 virus in the post-mortem period. Although the caution in choosing whether or not to perform an autopsy on infected corpses is acceptable, not to perform autopsies is not biologically supported.

Postmortem Swabs in the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: Report on 12 Complete Clinical Autopsy Cases.

CONTEXT.­: Clinical autopsies have historically provided a fundamental contribution in the definition of the clinicopathologic basis of infectious diseases. Even though we are witnessing the decline of the clinical autopsy, its importance remains unchanged as it is the most exhaustive way to investigate diseases. The identification of the virus in postmortem tissues is a fundamental step in the definition of its clinical features. OBJECTIVE.­: To investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in postmortem examination with swabs. DESIGN.­: We performed postmortem swabs in 12 autopsy cases of patients with a clinical diagnosis of SARS-CoV-2-related pneumonia. Our protocol consisted of a rhinopharyngeal and a tracheal swab in order to search for the virus in the upper airways, and of 2 swabs on the parenchyma of each lung. We also performed a fifth swab on the parenchyma of both lungs in order to search for other viruses that could evolve in a clinical picture of interstitial pneumonia. RESULTS.­: Overall, we found 9 of 12 cases had at least 1 postmortem swab positive for SARS-CoV-2. Moreover, we evaluated the time between the antemortem and postmortem swabs, the time between death and the postmortem swabs, and the time between the postmortem swabs and acceptance to the microbiology laboratory. Of note, we did not find a relationship between the results of the swabs and either the time elapsed from their collection or the time elapsed before their acceptance in the microbiology laboratory. CONCLUSIONS.­: A thorough knowledge of the eventual persistence of pathogens in deaths related to infectious diseases is fundamental for the safety of the operators during the autopsy practice, especially when referring to emergent pathogens, such as SARS-CoV-2. Our study highlights the importance in performing multiple swabs in the postmortem examination, because SARS-CoV-2 swab positivity can be limited to only a single swab.

Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

CONTEXT.­: The novel coronavirus disease 2019 (COVID-19) pandemic is significantly changing methodologic approaches in all branches of the health system. From a forensic point of view, this event is partly changing the manner in which forensic pathologists and all those who work in autopsy services operate, but above all, it is changing the patterns established for years by which cadavers are analyzed postmortem. OBJECTIVE.­: To present a review of the literature and a proposal for COVID-19 autopsy protocols. To contain the infection risk, a revision of all the protocols that until now have been applied to the examination of bodies that require autopsy services is required. DATA SOURCES.­: Currently, the diagnosis and postmortem analysis of positive or suspected COVID-19 cases plays a crucial role in scientific research. A review of the main recommendations proposed by international scientific societies regarding the risk of infection during autopsy was carried out. Scientific papers currently available via the PubMed NCBI search engine on COVID-19 postmortem diagnosis were also examined. CONCLUSIONS.­: Throughout the history of medicine, autopsy has been fundamental to the understanding of multiple pathogenic processes that are investigated postmortem. The purpose of the study is to propose an operating protocol that can be useful for all clinical and forensic autopsies, with particular reference to the correct methods to be applied to the examination of positive or suspected COVID-19 cases, regarding both the autopsy procedure and the collection and analysis of biological samples.