Causes of death of forensic autopsy cases tested positive for COVID-19 in Tokyo Metropolis, Japan.

BACKGROUND: The profile of deaths related to coronavirus disease of 2019 (COVID-19) that occurred outside the hospital in Japan remains unclear because of cautious stance on performing autopsies of COVID-19 positive cases. METHODS: Autopsy cases that tested positive for COVID-19 in the Tokyo Metropolis from April 2020 to July 2022 were handled by medical examiners (n = 41). Age, sex, medical history, autopsy findings, cause of death, postmortem computed tomography (PMCT) findings, and the causal relationship between death and COVID-19 were examined. RESULTS: The mean age of the deceased was 58.0 years (range: 28-96 years), and the study sample consisted of 33 males (80.5%) and 8 females (19.5%). The most frequent medical histories were hypertension (n = 7) and diabetes (n = 7), followed by mental disorders (n = 5). Nineteen cases showed a body mass index ≧25.0 (46.3%). The leading cause of death was pneumonia (n = 17), in which diffuse ground-glass opacification and/or consolidation was noted on PMCT. There were 26 deaths directly related to COVID-19 (63.4%), including pneumonia, myocarditis, laryngotracheobronchitis, and emaciation. The proportion of deaths directly related to COVID-19 was lower after 2022 (42.1%) than prior to 2022 (81.8%). CONCLUSION: Pneumonia was the leading cause of death in this study sample; however, the causes of death in COVID-19 positive cases varied, especially after 2022, when the omicron variant was dominant. Mortality statistics may be affected by viral mutations, and the results of this study further emphasize the need for autopsy because more differential diagnoses should be considered in the phase of the omicron variant.

Death from COVID-19 in a Fully Vaccinated Subject: A Complete Autopsy Report.

A correctly implemented and widely accepted vaccination campaign was the only truly effective weapon to reduce mortality and hospitalizations related to COVID-19. However, it was not 100% effective and has not eliminated COVID-19. Even though more than 60% of the worldwide population is fully vaccinated (meaning that these subjects have completed the recommended vaccine cycle), subjects continue to die from COVID-19, particularly in the presence of comorbidities. In this scenario, autopsies play a crucial role in understanding the pathophysiological mechanisms of SARS-CoV-2 in vaccinated subjects and adapting therapies accordingly. This case report analyzes the death of a fully vaccinated patient who suffered from comorbidities and died from COVID-19; we provide a complete autopsy data set. On microscopic examination, the lungs showed massive interstitial pneumonia, areas of inflammation with interstitial lympho-plasma cell infiltrate, and interstitial edema. The liver showed granulocytes within the hepatic parenchyma. All these elements were consistent with previous published data on unvaccinated patients who had died from COVID-19. The present study is the first that analyzes, through a complete autopsy and a microscopic analysis of all organs, a death related to COVID-19 despite vaccine administration. In this regard, to the best of our knowledge, no other studies have been published reporting a complete autopsy. This study reports, on the one hand, the importance of vaccination programs in the fight against COVID-19, and, on the other hand, it hypothesizes that the vaccine does not offer complete immunity to SARS-CoV-2, particularly in elderly subjects with comorbidities.

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.

Quantitative analysis of respiratory viral distribution in forensic autopsy cases.

Respiratory viruses can cause fatal systemic infections; therefore, post-mortem diagnosis is essential in forensic autopsy cases. However, little is known regarding the distribution of respiratory viruses in the body. In this study, we investigated the anatomical distribution of respiratory viruses in 48 forensic autopsy cases suspected of viral infections at our institute. Fast Track Diagnostics (FTD) Respiratory Pathogens 21 was used as a screening test for 20 respiratory viruses in nasopharyngeal swabs. In cases with positive results for virus detection by the screening test, the detected viruses were quantified in body fluid and organ specimens by virus-specific real-time reverse transcription polymerase chain reaction (RT-PCR) and digital PCR. Viruses were detected in 33 cases, with the viral distribution and load differing among the cases. Since various respiratory viruses were detected from the nasopharyngeal swab and its viral load was higher than those of other body fluid specimens, the nasopharyngeal swab was suggested as a useful specimen for the post-mortem detection of respiratory viruses. Viruses were detected in almost all specimens including the serum in six cases. Considering the viral distribution in the body, pathological findings, and ante-mortem symptoms, these cases were presumed to be systemically infected, having died in the acute infection phase. In conclusion, the anatomical distribution of respiratory viruses can help indicate ante-mortem systemic conditions and the cause of death.

Autopsy findings of post-COVID-19 vaccination deaths in Tokyo Metropolis, Japan, 2021.

BACKGROUND: COVID-19 vaccines have been used across Japan since 17 February 2021, and as of 17 April 2022, 1690 deaths potentially caused by vaccine-related adverse effects have been reported to the Ministry of Health, Labour and Welfare. However, the causal relationship between vaccination and death could not be fully evaluated because of a lack of sufficient information. METHODS: Autopsy cases in which deaths occurred within seven days after COVID-19 vaccination in Tokyo Metropolis and were handled by medical examiners were selected (n = 54). Age, sex, vaccine-related information, cause of death, and possible causal relationship between vaccination and death were examined. RESULTS: The mean age of the deceased individuals was 68.1 years, and the study sample consisted of 34 males (63.9%) and 20 females (37.0%). Thirty-seven and six individuals received Comirnaty and Spikevax, respectively (68.5% and 11.1% respectively). The manner of death included natural (n = 43), non-natural (n = 8), and undetermined (n = 3). The most frequent cause of death was ischemic heart disease (n = 16). Regarding causal relationships, 46 cases (85.2%) did not show a causal relationship to vaccination, except for myocarditis (n = 3), thrombosis-related death (n = 4), and others (n = 1). CONCLUSION: Although many cases of deaths after COVID-19 vaccination in this study showed no definite causal relationship between the vaccination and deaths, some cases showed possible adverse events such as myocarditis. Autopsies are essential for detecting vaccine-related deaths, and the Japanese death investigation system needs to be reinforced from this viewpoint.

Findings and inferences from full autopsies, minimally invasive autopsies and biopsy studies in patients who died as a result of COVID19 - A systematic review.

Many articles on COVID19 deaths have been published since the pandemic has occurred. On reviewing the articles published until June 2021, the findings were very heterogeneous. Adding to the existing knowledge, there were also some unique observations made in the pathogenesis of COVID19. This review was done to determine the findings obtained and inferences drawn from various studies published globally among patients who died due to COVID19. PRISMA guidelines were used to conduct this systematic review. A search of databases like PubMed, ScienceDirect and Epistemonikos was done. The articles focusing on postmortem sample studies involving full autopsies, minimally invasive autopsies and tissue biopsy studies were screened and searched. The studies included were all the case reports, case series, narrative reviews and systematic reviews obtained in full text and in the English language containing study information, and samples obtained postmortem. The information obtained was tabulated using Microsoft excel sheets. The duplicates were removed at the beginning of the tabulation. Zotero referencing software was used for article sorting and citation and bibliography. Two authors independently reviewed the articles throughout the process to prevent bias. Adding to the heterogeneity of COVID19, the concept of lethality in preexisting disease conditions, the occurrence of secondary bacterial and fungal infections, and other pathogenetic mechanisms uniquely encountered are to be considered in treating the patients. Also, the presence of SARS-CoV-2 postmortem is established and should be considered a hazard.

The role of psychological autopsy in investigating a case of atypical suicide in schizophrenia: a case report with a brief review of literature.

Background: Self-harm typically is without lethal intent. Death can occur rarely, with suicide taking on an atypical form that raises the suspicion of hetero-aggression. Our study aimed to identify the link between self-harm and suicide intent and also to outline the positive diagnosis of an atypical suicide case which has raised the suspicion of hetero-aggression. For this purpose, the psychological autopsy method should be used regularly in suicide investigation because it not only allows a positive diagnosis of suicide but can also provide a detailed picture of mental degradation and associated suicide risk factors. Case presentation: The case of a 26-year-old man from a rural area, found dead in the basement, at home, naked, barricaded inside, is described. Methods: The on-site investigation and a complete forensic autopsy were performed. In addition, we apply the psychological autopsy method which gathered enough information to outline the positive diagnosis of suicide. We also made a brief literature review on the suicide risk factors and the behavioral changes that occurred during the COVID-19 pandemic in schizophrenic patients. Results: The forensic autopsy revealed that he presented a complex craniofacial trauma as the cause of death (with scalp lacerations, frontal fracture, subarachnoid hemorrhage, and frontal cerebral contusions) associated with torso trauma (with self-inflicted stabbed wounds) with bruises and abrasions on the limbs. The injuries that caused death were self-inflicted and ensued repeatedly hitting his head against blunt objects. Using the psychological autopsy method, we found out that he presented multiple psychiatric hospitalizations for schizophrenia for almost 10 years, recently with reduced compliance to treatment. We also documented two previous suicide attempts and a gradual deterioration of his mental health. Conclusions: We highlighted the role of the psychological autopsy (in addition to the judicial investigation and the forensic autopsy) for the diagnosis of committed suicide, for making a rigorous differential diagnosis between accident, hetero-aggression, and suicide, and also in pin-pointing the suicide risk factors. Supplementary Information: The online version contains supplementary material available at 10.1186/s41935-022-00291-5.

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.

Cause of death based on systematic post-mortem studies in patients with positive SARS-CoV-2 tissue PCR during the COVID-19 pandemic.

IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.

Safe Management Strategies in Clinical Forensic Autopsies of Confirmed COVID-19 Cases.

To date, there is poor evidence on the transmission of infection in individuals handling the bodies of deceased persons infected with SARS-CoV-2 and in particular, during autopsies. The aim of this study was to demonstrate that when appropriate strategies are adopted autopsy is a safe procedure with a minimal infection risk for all subjects involved (pathologists, technical personnel, and others) when proper strategies are adopted. We performed 16 autopsies on cadavers of persons who had died with confirmed COVID-19 with different post-mortem intervals (PMI). To confirm the presence of SARS-CoV-2 RNA, for each autopsy, 2 swabs were sampled from lungs, while to evaluate environmental contamination, 11 swabs were taken at three different times: T0 (before autopsy), T1 (at the end of the autopsy, without removing the corpse), and T2 (after cleaning and disinfecting the autopsy room). Specifically, 2 swabs were sampled on face shields used by each pathologist, and 4 swabs were collected on the autopsy table; 4 swabs were also collected from walls and 1 from floor. Lung swabs confirmed the presence of SARS-CoV-2 RNA in all cases. Environmental swabs, collected at T0 and T2 were all negative, while swabs sampled at T1 were shown to be positive. Interestingly, no association was shown between PMI length and environmental contamination. Infection control strategies for safe management of clinical forensic autopsies of bodies with suspected or confirmed COVID-19 are also described.

Gross and histopathological pulmonary findings in a COVID-19 associated death during self-isolation.

Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase "acute respiratory distress syndrome" (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections.

SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns.

"Severe acute respiratory syndrome" (SARS) due to coronavirus (SARS-CoV-2) infection is a well-known cause of death. Sometimes, demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flu-like symptoms. In these doubtful cases, the forensic pathologist could be requested to define the cause of death occurred outside the hospital. In this report, the authors describe two autopsied cases of SARS-CoV-2-related deaths which occurred suddenly at home and were not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.