SARS-CoV-2-associated T-cell infiltration in the central nervous system.

Objectives: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Although an acute SARS-CoV-2 infection mainly presents with respiratory illness, neurologic symptoms and sequelae are increasingly recognised in the long-term treatment of COVID-19 patients. The pathophysiology and the neuropathogenesis behind neurologic complications of COVID-19 remain poorly understood, but mounting evidence points to endothelial dysfunction either directly caused by viral infection or indirectly by inflammatory cytokines, followed by a local immune response that may include virus-specific T cells. However, the type and role of central nervous system-infiltrating T cells in COVID-19 are complex and not fully understood. Methods: We analysed distinct anatomical brain regions of patients who had deceased as a result of COVID-19-associated pneumonia or complications thereof and performed T cell receptor Vß repertoire sequencing. Clonotypes were analysed for SARS-CoV-2 association using public TCR repertoire data. Results: Our descriptive study demonstrates that SARS-CoV-2-associated T cells are found in almost all brain areas of patients with fatal COVID-19 courses. The olfactory bulb, medulla and cerebellum were brain regions showing the most SARS-CoV-2 specific sequence patterns. Neuropathological workup demonstrated primary CD8+ T-cell infiltration with a perivascular infiltration pattern. Conclusion: Future research is needed to better define the relationship between T-cell infiltration and neurological symptoms and its long-term impact on patients' cognitive and mental health.

Concordance between MITS and conventional autopsies for pathological and virological diagnoses.

In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases.

Minimally Invasive Tissue Sampling via Post Mortem Ultrasound: A Feasible Tool (Not Only) in Infectious Diseases-A Case Report.

In the past years the number of hospital autopsies have declined steadily, becoming almost excluded from medical training. Medicolegal (forensic) autopsies account for almost all autopsies, whereas hospital autopsies are becoming increasingly rare. Minimally invasive tissue sampling (MITS) using post mortem ultrasound offers the opportunity to increase the number of post mortem examinations in a clinical and even forensic context. MITS is a needle-based post mortem procedure that uses (radiological) imaging techniques to examine major organs of the body, acquire tissue samples and aspirate fluid from the body cavities or hollow organs. In this study, MITS was used to determine the presence of other co-existing diseases in a deceased infected 97-year-old woman with severe acute respiratory syndrome coronavirus 2. The examination of her body was carried out using ultrasound as an imaging tool and to gather ultrasound-guided biopsies as conventional autopsy was rejected by the next of kin. Ultrasound and histology identified an intravesical mass leading to an obstruction of the urinary outlet resulting in bilateral hydronephrosis and purulent pyelonephritis, which was unknown during her lifetime. Histopathological examination revealed the tumor mass to be a squamous cell carcinoma. This study has shown that MITS can be used to determine the cause of death and the presence of concomitant diseases in the infectious deceased.

Vagus nerve inflammation contributes to dysautonomia in COVID-19.

Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.

Pilot study in Hamburg on the prevalence of SARS-CoV-2 infections and pandemic survey in the German funeral industry.

Funeral home and crematorium workers are an important occupational group in the corona crisis. The occupational setting led to concerns about an increased risk of infection with SARS-CoV-2. The seroprevalence in this occupational group is unclear. A questionnaire-based retrospective survey of funeral home and crematorium staff was conducted in December 2020. A second survey of funeral and crematorium staff was conducted 6 months later, in June 2021, to determine changes in pandemic management. Seroprevalence or vaccination status for SARS-CoV-2 was determined at these two time points. In December 2020, a seroprevalence of 2.3% (n = 1/44) was detected in funeral home and crematorium workers. In June 2021, one additional participant tested positive for the SARS-CoV-2 nucleocapsid. Of the participants, 48.5% (n = 16) were vaccinated at this time. The risk of SARS-CoV-2 infection for funeral home and crematorium workers is more similar to that of the general population in Hamburg, Germany. We found no evidence of an increased risk of infection at these two time points in our cohort. Further education on communicable diseases or appropriate protective measures in this occupational group for other infectious diseases would be useful in the future.

Semiautomatic assessment of endothelial density and morphology in organ-cultured corneas - potential predictors for transplantation suitability and clinical outcome?

BACKGROUND: The quality of the endothelial cell layer is a major criterion for the approval of organ-cultured human donor-corneas for transplantation. We wanted to compare the predictive capacities of initial endothelial density and endothelium cell morphology for the approval of donor corneas for transplantation and for the clinical outcome after transplantation. METHODS: The endothelial density and endothelium morphology in organ culture were examined by semiautomatic assessment of 1031 donor corneas. We performed a statistical analysis for correlations of donor-data and cultivation parameters regarding their predictive capacities for the final approval of donor corneas for transplantation and the clinical outcome of 202 transplanted patients. RESULTS: Corneal endothelium cell density proved to be the only parameter with a certain predictive capacity with regard to the final decision, whether donor corneas are suitable for transplantation - however, the correlation was low (area under the curve [AUC] = 0.655). Endothelial cell morphology lacked any predictive power (AUC = 0.597). The clinical outcome regarding visual acuity seemed to be largely independent from both corneal endothelial cell density and morphology. Sub-analyses on transplanted patients stratified for their diagnoses vindicated these findings. CONCLUSIONS: Higher endothelial density (above a cut-off level of 2000 cells/mm2), as well as better endothelial morphology do not seem to be critical for transplant-corneal functionality in organ culture and up to 2 years after transplantation. Comparable long-term studies on graft survival are recommended to determine, whether the present endothelial density cut-off levels might be too stringent.

[One and a half years of e-scooters in Hamburg]. / Eineinhalb Jahre E-Scooter ­ Zwischenbilanz in Hamburg: Teil 1: alkoholbedingte Auffälligkeiten im Straßenverkehr.

Background: Since electric scooters were introduced as an urban means of transportation in Hamburg in June 2019, a high number of violations of the current laws regarding alcohol consumption by e­scooter riders have been recorded. Objective: The aim of this study is to obtain an overview of traffic offences committed by e­scooter drivers under the influence of alcohol, to classify their relevance in relation to other road user groups, and to draw a first interim balance with respect to their frequency after 1.5 years. Material and methods: The data of all e­scooter drivers (n = 342) examined concerning their blood alcohol values analyzed at the Institute of Legal Medicine of the University Medical Centre Hamburg-Eppendorf between 15.06.2019 and 31.12.2020 were retrospectively evaluated with respect to their demographic information and the medical examination results. These were brought into context with the total number of offences against the road traffic regulations with subsequent blood alcohol measurement. Results: 9.6% of the total number of offences against the road traffic regulations in connection with subsequent determination of the blood alcohol concentration were committed by e­scooter drivers. 87.7% of those examined were male. The blood alcohol concentration was above the limit of 1.10 ‰ for absolute driving incapacity when using a passenger car in 76.9% of those examined. An accumulation of cases was particularly noticeable at night and at weekends.Due to imprecise records, a certain number of unreported e­scooter incidents can be assumed among the unspecified motor vehicles. Conclusion: As e­scooter drivers make up a considerable proportion of drunken road users and the accidents mostly occur at night and at weekends, increased education and, if necessary, a driving ban at these times would seem to make sense.

[One and a half years of e-scooters in Hamburg]. / Eineinhalb Jahre E-Scooter ­ Zwischenbilanz in Hamburg: Teil 2: Unfallcharakteristika.

Background: Since the spread of the so-called electric scooters (e-scooters) through rental services in Hamburg as of June 2019, accidents due to the use of this means of transportation have been regularly registered. The most frequent injury patterns among e­scooter riders involved accidents concerning the upper extremities and the head. There was a relevant accumulation of drunk drivers among the injured persons. Objective: The aim of the study is to compare injury patterns in drunk versus non-drunk e­scooter riders who had an accident. Material and methods: Data from the Department of Trauma Surgery at the University Medical Center Hamburg-Eppendorf were retrospectively analyzed for accidents involving e­scooters and the resulting injury patterns. For this purpose, the gender, age, injury pattern of the persons, the course of the accident, and information on previous alcohol consumption were recorded descriptively for the period from June 2019 to December 2021. Results: Drivers were on average 32 (interval: 15-88 years) years old and those under the influence of alcohol were predominantly male (69.9%). Accidents occurred mainly in summer and at night. Common injury patterns were injuries to the face, head, and extremities. Conclusion: It should be noted that injuries to the face and head occurred more frequently under the influence of alcohol than in the cohort without alcohol. Education about the health and legal consequences of riding an e­scooter under the influence of alcohol should be provided to all users. In addition, wearing a helmet or banning driving at night are possible measures to reduce accidents associated with drunk riding.

Young COVID-19 Patients Show a Higher Degree of Microglial Activation When Compared to Controls.

The severe acute respiratory syndrome-corona virus type 2 (SARS-CoV-2) is the cause of human coronavirus disease 2019 (COVID-19). Since its identification in late 2019 SARS-CoV-2 has spread rapidly around the world creating a global pandemic. Although considered mainly a respiratory disease, COVID-19 also encompasses a variety of neuropsychiatric symptoms. How infection with SARS-CoV-2 leads to brain damage has remained largely elusive so far. In particular, it has remained unclear, whether signs of immune cell and / or innate immune and reactive astrogliosis are due to direct effects of the virus or may be an expression of a non-specific reaction of the brain to a severe life-threatening disease with a considerable proportion of patients requiring intensive care and invasive ventilation activation. Therefore, we designed a case-control-study of ten patients who died of COVID-19 and ten age-matched non-COVID-19-controls to quantitatively assess microglial and astroglial response. To minimize possible effects of severe systemic inflammation and / or invasive therapeutic measures we included only patients without any clinical or pathomorphological indication of sepsis and who had not been subjected to invasive intensive care treatment. Our results show a significantly higher degree of microglia activation in younger COVID-19 patients, while the difference was less and not significant for older COVID-19 patients. The difference in the degree of reactive gliosis increased with age but was not influenced by COVID-19. These preliminary data warrants further investigation of larger patient cohorts using additional immunohistochemical markers for different microglial phenotypes.

Robotic Tissue Sampling for Safe Post-Mortem Biopsy in Infectious Corpses.

In pathology and legal medicine, the histopathological and microbiological analysis of tissue samples from infected deceased is a valuable information for developing treatment strategies during a pandemic such as COVID-19. However, a conventional autopsy carries the risk of disease transmission and may be rejected by relatives. We propose minimally invasive biopsy with robot assistance under CT guidance to minimize the risk of disease transmission during tissue sampling and to improve accuracy. A flexible robotic system for biopsy sampling is presented, which is applied to human corpses placed inside protective body bags. An automatic planning and decision system estimates optimal insertion point. Heat maps projected onto the segmented skin visualize the distance and angle of insertions and estimate the minimum cost of a puncture while avoiding bone collisions. Further, we test multiple insertion paths concerning feasibility and collisions. A custom end effector is designed for inserting needles and extracting tissue samples under robotic guidance. Our robotic post-mortem biopsy (RPMB) system is evaluated in a study during the COVID-19 pandemic on 20 corpses and 10 tissue targets, 5 of them being infected with SARS-CoV-2. The mean planning time including robot path planning is 5.72±167s. Mean needle placement accuracy is 7.19± 422mm.

Post-mortem histopathology of pituitary and adrenals of COVID-19 patients.

BACKGROUND: Knowledge of the exact organ manifestation is essential for a comprehensive understanding of COVID-19 infection. Here, the histopathological changes in the pituitary and adrenal glands were analyzed. METHODS: In this series, the formalin-fixed tissues of 63 pituitary glands and 50 adrenal glands were examined. We performed HE and PAS staining and examined COVID-19 nucleocapsid antibody immunohistochemically in the pituitary glands and adrenals. RESULTS: Histologically, there was no evidence of COVID-19-specific changes in the pituitary and adrenal glands. Large pituitary necrosis may be interpreted as a shock reaction. Independent of infection, we found one T-cell lymphoma, two adenomas, and four Rathke-type cysts in the pituitary glands, and 70% of the adrenal glands showed decreased lipid content and an increase in compact cells as a stress response. In addition, a cortical adenoma in one adrenal gland and small cortical nodules in three adrenal glands were detected independently of COVID-19. CONCLUSION: Pituitary and adrenal glands do not appear histologically predominant in the course of COVID-19.

Dismemberment and Body Encasement-Case Report and an Empiric Study.

The mutilation and encasement of corpses are rare in daily forensic work, but when they occur, close cooperation between different disciplines, such as legal medicine and forensic anthropology, is necessary to obtain the most valuable results. One forensic examination method is the radiological evaluation of victims or body parts by postmortem CT (pmCT) and X-ray images. In relation to a case described in this paper, an empirical study was conducted to figure out the value of radiological imaging and the ability to visualize and temporally classify changes in a corpse encased in concrete. For this purpose, the head and paw of a pig were encased in concrete and scanned regularly over a period of one year. Body parts such as the head and paw are clearly visible on X-ray images. Although decay-related changes are shown, a specific minimum time interval cannot yet be found, as these changes occur continuously in lesser amounts.

Forensic biomarkers of lethal traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and its accurate diagnosis is an important concern of daily forensic practice. However, it can be challenging to diagnose TBI in cases where macroscopic signs of the traumatic head impact are lacking and little is known about the circumstances of death. In recent years, several post-mortem studies investigated the possible use of biomarkers for providing objective evidence for TBIs as the cause of death or to estimate the survival time and time since death of the deceased. This work systematically reviewed the available scientific literature on TBI-related biomarkers to be used for forensic purposes. Post-mortem TBI-related biomarkers are an emerging and promising resource to provide objective evidence for cause of death determinations as well as survival time and potentially even time since death estimations. This literature review of forensically used TBI-biomarkers revealed that current markers have low specificity for TBIs and only provide limited information with regards to survival time estimations and time since death estimations. Overall, TBI fatality-related biomarkers are largely unexplored in compartments that are easily accessible during autopsies such as urine and vitreous humor. Future research on forensic biomarkers requires a strict distinction of TBI fatalities from control groups, sufficient sample sizes, combinations of currently established biomarkers, and novel approaches such as metabolomics and mi-RNAs.

The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2.

Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.

Detection of SARS-CoV-2 genomic and subgenomic RNA in retina and optic nerve of patients with COVID-19.

PURPOSE: Presence of SARS-CoV-2 RNA in human retinal biopsies (RBs) was previously reported by us. In this consecutive study, we analysed RB and optic nerve biopsies (ONBs) in deceased patients with confirmed COVID-19 assessing viral RNA load, possible virus replication and infectivity. PATIENTS AND METHODS: In this case series, 14 eyes of 14 deceased patients with COVID-19 were enucleated during autopsy. RB and ONB were subjected to molecular detection of viral RNA, virus cultivation and immunohistochemistry. SARS-CoV-2 RNA loads were compared with RNA loads in the respective throat swabs, vitreous humour and blood samples. RESULTS: SARS-CoV-2 RNA was detected in 7/14 RBs and in 10/13 ONBs. While virus isolation failed and immunohistochemistry of SARS-CoV-2 spike protein was negative, subgenomic RNA (sgRNA) was detectable (40% RB; 60% ONB). CONCLUSION: SARS-CoV-2 RNA is detectable in RB and ONB of patients with COVID-19. Presence of sgRNA could point to a SARS-CoV-2 infection of neuronal tissue, but as virus isolation failed and immunohistochemistry of SARS-CoV-2 spike protein was negative, an active infection seems unlikely.

Cardiac SARS-CoV-2 infection is associated with pro-inflammatory transcriptomic alterations within the heart.

AIMS: Cardiac involvement in COVID-19 is associated with adverse outcome. However, it is unclear whether cell-specific consequences are associated with cardiac SARS-CoV-2 infection. Therefore, we investigated heart tissue utilizing in situ hybridization, immunohistochemistry, and RNA-sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19. METHODS AND RESULTS: In this study, 95 SARS-CoV-2-positive autopsy cases were included. A relevant SARS-CoV-2 virus load in the cardiac tissue was detected in 41/95 deceased (43%). Massive analysis of cDNA ends (MACE)-RNA-sequencing was performed to identify molecular pathomechanisms caused by the infection of the heart. A signature matrix was generated based on the single-cell dataset 'Heart Cell Atlas' and used for digital cytometry on the MACE-RNA-sequencing data. Thus, immune cell fractions were estimated and revealed no difference in immune cell numbers in cases with and without cardiac infection. This result was confirmed by quantitative immunohistological diagnosis. MACE-RNA-sequencing revealed 19 differentially expressed genes (DEGs) with a q-value <0.05 (e.g. up: IFI44L, IFT3, TRIM25; down: NPPB, MB, MYPN). The upregulated DEGs were linked to interferon pathways and originate predominantly from endothelial cells. In contrast, the downregulated DEGs originate predominately from cardiomyocytes. Immunofluorescent staining showed viral protein in cells positive for the endothelial marker ICAM1 but rarely in cardiomyocytes. The Gene Ontology (GO) term analysis revealed that downregulated GO terms were linked to cardiomyocyte structure, whereas upregulated GO terms were linked to anti-virus immune response. CONCLUSION: This study reveals that cardiac infection induced transcriptomic alterations mainly linked to immune response and destruction of cardiomyocytes. While endothelial cells are primarily targeted by the virus, we suggest cardiomyocyte destruction by paracrine effects. Increased pro-inflammatory gene expression was detected in SARS-CoV-2-infected cardiac tissue but no increased SARS-CoV-2 associated immune cell infiltration was observed.

Dying of VOC-202012/01 - multimodal investigations in a death case of the SARS-CoV-2 variant.

The current pandemic with Severe acute respiratory syndrome-coronavirus-2 has been taking on new dynamics since the emergence of new variants last fall, some of them spreading more rapidly. Many countries currently find themselves in a race to ramp up vaccination strategies that have been initiated and a possible third wave of the pandemic from new variants, such as the Variant of Concern-202012/01 from the B.1.1.7 lineage. Until today, many investigations in death cases of Coronavirus-disease-19 have been conducted, revealing pulmonary damage to be the predominant feature of the disease. Thereby, different degrees of macroscopic and microscopic lung damage have been reported, most of them resembling an Acute Respiratory Distress Syndrome. Far more, systemic complications of the disease such as pulmonary embolisms have been described. However, neither morphologic nor virologic findings of patients dying of the new variants have yet been reported. Here, we report on a comprehensive analysis of radiologic, morphologic, and virologic findings in a fatal case of this variant.

Prospective postmortem evaluation of 735 consecutive SARS-CoV-2-associated death cases.

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.

Landscape of T-cell repertoires with public COVID-19-associated T-cell receptors in pre-pandemic risk cohorts.

OBJECTIVES: T cells have an essential role in the antiviral defence. Public T-cell receptor (TCR) clonotypes are expanded in a substantial proportion of COVID-19 patients. We set out to exploit their potential use as read-out for COVID-19 T-cell immune responses. METHODS: We searched for COVID-19-associated T-cell clones with public TCRs, as defined by identical complementarity-determining region 3 (CDR3) beta chain amino acid sequence that can be reproducibly detected in the blood of COVID-19 patients. Of the different clonotype identification algorithms used in this study, deep sequencing of brain tissue of five patients with fatal COVID-19 delivered 68 TCR clonotypes with superior representation across 140 immune repertoires of unrelated COVID-19 patients. RESULTS: Mining of immune repertoires from subjects not previously exposed to the virus showed that these clonotypes can be found in almost 20% of pre-pandemic immune repertoires of healthy subjects, with lower representation in repertoires from risk groups like individuals above the age of 60 years or patients with cancer. CONCLUSION: Together, our data show that at least a proportion of the SARS-CoV-2 T-cell response is mediated by public TCRs that are present in repertoires of unexposed individuals. The lower representation of these clones in repertoires of risk groups or failure to expand such clones may contribute to more unfavorable clinical COVID-19 courses.

Ultrasound in legal medicine-a missed opportunity or simply too late? A narrative review of ultrasonic applications in forensic contexts.

OBJECTIVES: Conventional autopsies remain the gold standard of postmortem healthcare quality assurance and help gathering extended knowledge on diseases. In answer to constantly declining autopsy rates non- or minimally invasive autopsy methods were introduced. Ultrasound is a well-established tool for imaging commonly used in clinical practice. This narrative review aims to summarize the current literature regarding the feasibility and validity of ultrasound in a forensic context. MATERIAL AND METHODS: A PubMed database search was carried out. Abstracts were scanned for pre-defined ex- and inclusion criteria, followed by a snowball search procedure applied to the primarily included articles. RESULTS: Forty-five publications met our inclusion criteria. The selected articles concern the feasibility of ultrasound in pre- or postmortem settings, forensic age estimation, and minimally invasive approaches. For imaging, ultrasound was deemed a reliable tool for the examination of epiphyses und superficial wounds, with limitations regarding internal organs and image quality due to postmortem changes. Ultrasound-guided minimally invasive approaches yielded higher success rates for adequate tissue sampling. Many investigations were carried out in low- and middle-income countries focusing on infectious diseases. CONCLUSION: Ultrasound seems a promising but underutilized imaging tool in legal medicine to date. Promising approaches on its feasibility have been conducted. Especially for minimally invasive methods, ultrasound offered significant improvements on qualified biopsy sampling and thus appropriate diagnostics. Moreover, ultrasonic evaluation of epiphyses for age estimation offered valuable results. Nevertheless, further assessment of ultrasonic feasibility in forensic contexts is needed.