Pulmonary pathology of COVID-19: a review of autopsy studies.

PURPOSE OF REVIEW: COVID-19 lung injury is a common manifestation of severe illness. Lung tissue examination has been largely derived from autopsy - a combination of case reports, small and moderately sized series with international scope. Common and uncommon histopathology provides insight into the progression of severe, fatal disease. RECENT FINDINGS: COVID-19 lung histology is most commonly diffuse alveolar damage as part of acute respiratory distress syndrome. Lung injury can be temporally heterogeneous, with patterns of healing alongside new injury. Viral studies, including immunohistochemistry, RNA in-situ hybridization, and tissue-based Polymerase chain reaction (PCR) assist in discerning complications of therapy (e.g. ventilator-associated pneumonia) from primary viral-induced injury. Response to viral infection produces systemic effects, and one major manifestation is thrombosis of micro-circulation and larger vessels. Less common patterns include neutrophil-rich inflammation, raising speculation that neutrophil extra-cellular traps may play a role in both viral control and exaggerated immune response. SUMMARY: The heterogeneity of fatal cases- persistence of viral infection in lung, clearance of virus but severe lung injury, thrombosis, and exaggerated immune response - suggest that antiviral, antithrombotic, anti-inflammatory, and supportive therapy play a role in treatment, but that the patient-specific cause and timing of the lung injury is important in choosing intervention.

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.

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

Verbal Autopsy as a Tool for Defining Causes of Death in Specific Healthcare Contexts: Study of Applicability through a Traditional Literature Review.

Autopsy examination, the gold standard for defining causes of death, is often difficult to apply in certain health care settings, especially in developing countries. The COVID-19 pandemic and its associated difficulties in terms of implementing autopsy examinations have made the need for alternative means of determining causes of death even more evident. One of the most interesting alternatives to the conventional autopsy is the verbal autopsy, a tool that originated in Africa and Asia in the 1950s and consists of a structured interview with the deceased's family members concerning the symptoms manifested by the person and the circumstances of death. In the early 1990s, the first doubts emerged about the validity of verbal autopsies, especially about the real reliability of the cause of death identified through this tool. The objective of the review was to identify studies that had assayed the validity of verbal autopsies through a rigorous comparison of the results that emerged from it with the results of conventional autopsies. When starting from an initial pool of 256 articles, only 2 articles were selected for final review. These are the only two original research articles in which a verbal autopsy validation process was performed by employing the full diagnostic autopsy as the gold standard. The two papers reached opposite conclusions, one suggesting adequate validity of verbal autopsy in defining the cause of death and the other casting serious doubts on the real applicability of this tool. Verbal autopsy undoubtedly has extraordinary potential, especially in the area of health and demographic surveillance, even considering the implementation that could result from the use of artificial intelligence and deep learning. However, at present, there appears to be a lack of solid data to support the robust reliability of this tool in defining causes of death.

Conducting verbal autopsy by telephone interview during the pandemic to support mortality surveillance: a feasibility study in Malaysia.

Objective: Verbal autopsy (VA) through face-to-face interviews with caregivers is a way to determine cause of death without medical certification. In Malaysia, the use of VA has improved mortality statistics. However, during the coronavirus disease 2019 (COVID-19) pandemic, face-to-face interviews were delayed, reducing VA data collection and affecting data for mortality surveillance. This study aims to investigate the feasibility and acceptability of conducting VA interviews via telephone calls, and the quality of the data gathered. Methods: The study was conducted in Malaysia from September to October 2020 using a cross-sectional design. Participants were health-care workers from established VA teams across the country. They conducted VA interviews via telephone and provided feedback through a customized online form. Data collected from the form were used to assess the feasibility, acceptability and quality of the telephone interviews using IBM SPSS version 23. Results: Responses were received from 113 participants. There were 74 (65.5%) successful interviews, representing 91% of the 81 cases who were able to be contacted. More than two thirds of health-care workers provided positive feedback on the telephone interview method for themselves and the interviewees. Only 10.8% of causes of death were unusable. Discussion: This study provides preliminary evidence that VA via telephone interview is feasible, acceptable and can be used as an alternative to face-to-face interviews without affecting data quality. During times when face-to-face interviews are not advisable, VA telephone interviews can be used for data collection for mortality surveillance.

Central nervous system autopsy - a neuropathological procedure based on multidisciplinary pathoclinical cooperation.

INTRODUCTION: Neuropathological brain and spinal cord post mortem examination is a distinct procedure that still plays an important role in modern medicine. In front of increasing amounts of clinical and genetic data, together with important developments in the field of neuroimaging, the Polish Association of Neuropathologists have updated their recommendations regarding central nervous system (CNS) examination. These guidelines are aimed at neuropathologists, pathologists and clinicians. AIM OF THE STUDY: Presentation of the outlined recommendations as their goal is to improve the quality, informativity, and cost effectiveness of CNS post mortem examinations. A comprehensive study of the literature was conducted to provide a clinical background of neuropathological autopsy. There are numerous open questions in neuroscience, and new strategies are required to foster research in CNS diseases. These include the challenge of organizing brain banks tasked with managing and protecting detailed multidisciplinary information about their resources. Complex neuropathological analyses of post mortem series are also important to assess the effectiveness of diagnostics and therapy, identify environmental impact on the development of neurological disorders, and improve public health policy. The recommendations outline the need for collaboration between multiple specialists to establish the proper diagnosis and to broaden knowledge of neurological disorders.

Potentials of post-mortem CT investigations during SARS-COV-2 pandemic: a narrative review.

In December 2019, a new coronavirus, SARS-COV-2, caused a cluster of cases of pneumonia in China, and rapidly spread across the globe. It was declared a pandemic by the World Health Organization on March 11th, 2020. Virtual autopsy by post-mortem CT (PMCT) and its ancillary techniques are currently applied in post-mortem examinations as minimally or non-invasive techniques with promising results. In this narrative review, we speculate on the potentials of PMCT and its ancillary techniques, as a viable investigation technique for analysis of suspected or confirmed SARS-COV-2 deaths. An online literature search was performed by using three prefix search terms (postmortem, post-mortem, post mortem) individually combined with the suffix radiology, imaging, computed tomography, CT and with the search terms 'SARS-CoV-2' and 'COVID-19' to identify papers about PMCT and its ancillary techniques in SARS-COV-2 positive cadavers. PMCT findings suggestive for pulmonary COVID-19 in deceased positive SARS-COV-2 infection are reported in the literature. PMCT ancillary techniques were never applied in such cases. PMCT imaging of the lungs has been proposed as a pre-autopsy screening method for SARS-COV-2 infection. Further studies are needed to ascertain the value of PMCT in determining COVID-19 as the cause of death without autopsy histopathological confirmation. We advocate the application of PMCT techniques in the study of ascertained or suspected SARS-COV-2 infected deceased individuals as a screening technique and as a method of post-mortem investigation, to augment the numbers of case examined and significantly reducing infection risk for the operators.

Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb.

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.

A case of persistent severe sequelae of COVID-19 infection: potential role in sudden death?

Depending on the stage of the disease, autopsy findings of COVID-19 may include a spectrum of cardiopulmonary pathologies including alveolar hyaline membrane formation, vascular thrombosis, and intracardiac thrombi. Identification of a COVID-19 positive decedent in the absence of clinical history relies primarily on post-mortem nasopharyngeal (NP) or oropharyngeal (OP) swabs for real time polymerase chain reaction (RT-PCR). In the absence of definitive microbiology testing, post-mortem computed tomography (PMCT) may be a powerful adjunct tool for screening. Persistence of pathological changes may prolong physiological alterations and increase the risk of cardiopulmonary compromise. This current case outlines the forensic presentation, utilization of screening tools including PMCT, and the autopsy findings of a recent toxicology related sudden death case in the context of severe sequelae of COVID-19 pneumonia. This case demonstrates the limitation of NP and OP swabs in the post-mortem setting, the value of PMCT as an adjunct screening tool, and raises the consideration of COVID-19 sequelae as a potential contributing risk factors in sudden death cases in the community.

Use of post-mortem chest computed tomography in Covid-19 pneumonia.

BACKGROUND AND AIM: COVID-19 is an extremely challenging disease, both from a clinical and forensic point of view, and performing autopsies of COVID-19 deceased requires adequately equipped sectorial rooms and exposes health professionals to the risk of contagion. Among one of the categories that are most affected by SARS-Cov-2 infection are the elderly residents. Despite the need for prompt diagnoses, which are essential to implement all isolation measures necessary to contain the infection spread, deceased subjects in long-term care facilities are still are often diagnosed post-mortem. In this context, our study focuses on the use of post-mortem computed tomography for the diagnosis of COVID-19 infection, in conjunction with post-mortem swabs. The aim of this study was to assess the usefulness of post-mortem whole CT-scanning in identifying COVID-19 pneumonia as a cause of death, by comparing chest CT-findings of confirmed COVID-19 fatalities to control cases. MATERIALS AND METHODS: The study included 24 deceased subjects: 13 subjects coming from long-term care facility and 11 subjects died at home. Whole body CT scans were performed within 48 h from death in all subjects to evaluate the presence and distribution of pulmonary abnormalities typical of COVID-19-pneumonia, including: ground-glass opacities (GGO), consolidation, and pleural effusion to confirm the post-mortem diagnosis. RESULTS: Whole-body CT scans was feasible and allowed a complete diagnosis in all subjects. In 9 (69%) of the 13 cases from long-term care facility the cause of death was severe COVID 19 pneumonia, while GGO were present in 100% of the study population. CONCLUSION: In the context of rapidly escalating COVID-19 outbreaks, given that laboratory tests for the novel coronavirus is time-consuming and can be falsely negative, the post-mortem CT can be considered as a reliable and safe modality to confirm COVID-19 pneumonia. This is especially true for specific postmortem chest CT-findings that are rather characteristic of COVID-19 fatalities.

Tissue-based SARS-CoV-2 detection in fatal COVID-19 infections: Sustained direct viral-induced damage is not necessary to drive disease progression.

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although viral infection is known to trigger inflammatory processes contributing to tissue injury and organ failure, it is unclear whether direct viral damage is needed to sustain cellular injury. An understanding of pathogenic mechanisms has been handicapped by the absence of optimized methods to visualize the presence and distribution of SARS-CoV-2 in damaged tissues. We first developed a positive control cell line (Vero E6) to validate SARS-CoV-2 detection assays. We then evaluated multiple organs (lungs, kidneys, heart, liver, brain, intestines, lymph nodes, and spleen) from fourteen COVID-19 autopsy cases using immunohistochemistry (IHC) for the spike and the nucleoprotein proteins, and RNA in situ hybridization (RNA ISH) for the spike protein mRNA. Tissue detection assays were compared with quantitative polymerase chain reaction (qPCR)-based detection. SARS-CoV-2 was histologically detected in the Vero E6 positive cell line control, 1 of 14 (7%) lungs, and none (0%) of the other 59 organs. There was perfect concordance between the IHC and RNA ISH results. qPCR confirmed high viral load in the SARS-CoV-2 ISH-positive lung tissue, and absent or low viral load in all ISH-negative tissues. In patients who die of COVID-19-related organ failure, SARS-CoV-2 is largely not detectable using tissue-based assays. Even in lungs showing widespread injury, SARS-CoV-2 viral RNA or proteins were detected in only a small minority of cases. This observation supports the concept that viral infection is primarily a trigger for multiple-organ pathogenic proinflammatory responses. Direct viral tissue damage is a transient phenomenon that is generally not sustained throughout disease progression.

Pathological findings in organs and tissues of patients with COVID-19: A systematic review.

BACKGROUND: Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs. METHODS AND FINDINGS: A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings. CONCLUSIONS: The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

Improvement in plasma D-dimer level in severe SARS-CoV-2 infection can be an indicator of fibrinolysis suppression: Case reports.

RATIONALE: Fibrinolysis shutdown associated with severe thrombotic complications is a recently recognized syndrome that was previously seldom investigated in patients with severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It presents a unique therapeutic dilemma, as anticoagulation with heparin alone is insufficient to address the imbalance in fibrinolysis. And while the use of fibrinolytic agents could limit the disease severity, it is often associated with bleeding complications. There is a need for biomarkers that will guide the timely stratification of patients into those who may benefit from both anticoagulant and fibrinolytic therapies. PATIENT CONCERNS: All 3 patients presented with shortness of breath along with comorbidities predisposing them to severe SARS-CoV-2 infection. One patient (Patient 3) also suffered from bilateral deep venous thrombosis. DIAGNOSES: All 3 patients tested positive for SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) and were eventually diagnosed with respiratory failure necessitating intubation. INTERVENTIONS: All 3 patients required mechanical ventilation support, 2 of which also required renal replacement therapy. All 3 patients were also placed on anticoagulation therapy. OUTCOMES: In Patients 1 and 2, the initial D-dimer levels of 0.97 µg/ml fibrinogen equivalent units (FEU) and 0.83 µg/ml FEU were only slightly elevated (normal <0.50 µg/ml FEU). They developed rising D-dimer levels to a peak of 13.21 µg/ml FEU and >20.0 µg/ml FEU, respectively, which dropped to 1.34 µg/ml FEU 8 days later in Patient 1 and to 2.94 µg/ml on hospital day 13 in Patient 2. In Patient 3, the D-dimer level on admission was found to be elevated to >20.00 µg/ml FEU together with imaging evidence of thrombosis. And although he received therapeutic heparin infusion, he still developed pulmonary embolism (PE) and his D-dimer level declined to 5.91 µg/ml FEU. Despite "improvement" in their D-dimer levels, all 3 patients succumbed to multi-system organ failure. On postmortem examination, numerous arterial and venous thromboses of varying ages, many consisting primarily of fibrin, were identified in the lungs of all patients. LESSONS: High D-dimer levels, with subsequent downtrend correlating with clinical deterioration, seems to be an indicator of fibrinolysis suppression. These findings can help form a hypothesis, as larger cohorts are necessary to demonstrate their reproducibility.

Characterisation of cardiac pathology in 23 autopsies of lethal COVID-19.

While coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, pathophysiological changes of the cardiovascular system remain to be elucidated. We performed a retrospective cardiopathological analysis of the heart and vasculature from 23 autopsies of COVID-19 patients, comparing the findings with control tissue. Myocardium from autopsies of COVID-19 patients was categorised into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive (n = 14) or negative (n = 9) based on the presence of viral RNA as determined by reverse transcriptase polymerase chain reaction (RT-PCR). Control tissue was selected from autopsies without COVID-19 (n = 10) with similar clinical sequelae. Histological characteristics were scored by ordinal and/or categorical grading. Five RT-PCR-positive cases underwent in situ hybridisation (ISH) for SARS-CoV-2. Patients with lethal COVID-19 infection were mostly male (78%) and had a high incidence of hypertension (91%), coronary artery disease (61%), and diabetes mellitus (48%). Patients with positive myocardial RT-PCR died earlier after hospital admission (5 versus 12 days, p < 0.001) than patients with negative RT-PCR. An increased severity of fibrin deposition, capillary dilatation, and microhaemorrhage was observed in RT-PCR-positive myocardium than in negatives and controls, with a positive correlation amongst these factors All cases with increased cardioinflammatory infiltrate, without myocyte necrosis (n = 4) or with myocarditis (n = 1), were RT-PCR negative. ISH revealed positivity of viral RNA in interstitial cells. Myocardial capillary dilatation, fibrin deposition, and microhaemorrhage may be the histomorphological correlate of COVID-19-associated coagulopathy. Increased cardioinflammation including one case of myocarditis was only detected in RT-PCR-negative hearts with significantly longer hospitalisation time. This may imply a secondary immunological response warranting further characterisation.

Application of photogrammetry in forensic pathology education of medical students in response to COVID-19.

As the coronavirus disease 2019 (COVID-19) pandemic forced universities to switch to distance online education, there was an urgent need to find some virtual/digital alternatives in order to continue teaching. Opportunities such as watching pre-recorded autopsy videos or creating and analyzing post-mortem computed tomography or magnetic resonance imaging with various 3D surface imaging techniques are usually time-consuming and cost-intensive. Photogrammetry, which allows the creation of 3D textured surface models from a series of overlapping photographs taken from varying viewpoints, is a less common approach compared with post-mortem imaging. We created 3D autopsy case models for a special online forensic pathology course in which students could try the models. Then, formal feedback was requested regarding the possible application of this method in education. Most of the students were satisfied with the new method and ranked photogrammetry higher than the other available methods. Our results indicate that photogrammetry has a high potential in undergraduate education, especially in the case of distance education or in those countries where declining autopsy rates have resulted in a decline in the use of the autopsy as an educational tool. Photogrammetry can also be used as a supplementary tool in traditional autopsy-based education and has potential applications in various fields of medical education.

Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19).

Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.