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1.
Neurol Neurochir Pol ; 56(2): 118-130, 2022.
Article in English | MEDLINE | ID: covidwho-1887304

ABSTRACT

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.


Subject(s)
Central Nervous System Diseases , Neuropathology , Autopsy/methods , Brain/pathology , Central Nervous System Diseases/pathology , Humans , Neuroimaging
2.
Radiol Med ; 127(4): 383-390, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1712323

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Autopsy/methods , Humans , Pandemics , Tomography, X-Ray Computed/methods
3.
Cell ; 184(24): 5932-5949.e15, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1549679

ABSTRACT

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.


Subject(s)
Autopsy/methods , COVID-19/mortality , COVID-19/virology , Olfactory Bulb/virology , Olfactory Mucosa/virology , Respiratory Mucosa/virology , Aged , Anosmia , COVID-19/physiopathology , Endoscopy/methods , Female , Glucuronosyltransferase/biosynthesis , Humans , Immunohistochemistry , In Situ Hybridization , Male , Microscopy, Fluorescence , Middle Aged , Olfaction Disorders , Olfactory Receptor Neurons/metabolism , Respiratory System , SARS-CoV-2 , Smell
5.
Forensic Sci Med Pathol ; 18(1): 69-73, 2022 03.
Article in English | MEDLINE | ID: covidwho-1474132

ABSTRACT

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.


Subject(s)
COVID-19 , Autopsy/methods , COVID-19/complications , Cause of Death , Death, Sudden/etiology , Humans , Tomography, X-Ray Computed/methods
7.
Forensic Sci Int ; 325: 110851, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1244737

ABSTRACT

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.


Subject(s)
COVID-19/diagnosis , Lung/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Autopsy/methods , Case-Control Studies , Female , Humans , Male , Middle Aged , Pleural Effusion/diagnostic imaging , Retrospective Studies , Sensitivity and Specificity , Whole Body Imaging
8.
Hum Pathol ; 114: 110-119, 2021 08.
Article in English | MEDLINE | ID: covidwho-1213257

ABSTRACT

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.


Subject(s)
COVID-19/pathology , Liver/virology , Lung/virology , SARS-CoV-2/pathogenicity , Animals , Autopsy/methods , COVID-19/virology , Chlorocebus aethiops , Disease Progression , Humans , Immunohistochemistry/methods , Liver/chemistry , Liver/pathology , Lung/pathology , RNA, Viral/metabolism , Vero Cells/virology , Viral Load/methods
9.
PLoS One ; 16(4): e0250708, 2021.
Article in English | MEDLINE | ID: covidwho-1206200

ABSTRACT

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.


Subject(s)
COVID-19/metabolism , COVID-19/physiopathology , Autopsy/methods , Biopsy/methods , Central Nervous System/virology , Endothelial Cells/virology , Female , Gastrointestinal Tract/virology , Heart/virology , Humans , Kidney/virology , Liver/virology , Lung/virology , Pandemics/statistics & numerical data , Placenta/virology , Pregnancy , SARS-CoV-2/pathogenicity , Staining and Labeling/methods , Trachea/virology
10.
Medicine (Baltimore) ; 100(15): e25255, 2021 Apr 16.
Article in English | MEDLINE | ID: covidwho-1180670

ABSTRACT

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.


Subject(s)
Anticoagulants/therapeutic use , COVID-19 , Fibrin Fibrinogen Degradation Products/analysis , Multiple Organ Failure , Thrombolytic Therapy/methods , Autopsy/methods , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , COVID-19/therapy , Clinical Deterioration , Female , Fibrinolysis , Humans , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/diagnosis , Multiple Organ Failure/etiology , Predictive Value of Tests , Prognosis , Renal Replacement Therapy/methods , Respiration, Artificial/methods , SARS-CoV-2/isolation & purification , Severity of Illness Index , Venous Thrombosis/blood , Venous Thrombosis/complications , Venous Thrombosis/diagnosis
11.
J Pathol Clin Res ; 7(4): 326-337, 2021 07.
Article in English | MEDLINE | ID: covidwho-1173791

ABSTRACT

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.


Subject(s)
COVID-19/pathology , COVID-19/virology , Respiratory System/pathology , Respiratory System/virology , SARS-CoV-2/pathogenicity , Adult , Autopsy/methods , COVID-19/complications , Female , Humans , Male , Middle Aged , Myocarditis/etiology , Myocarditis/pathology , Myocardium/pathology , RNA, Viral/genetics
12.
J Forensic Sci ; 66(4): 1533-1537, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1150072

ABSTRACT

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.


Subject(s)
Education, Distance/methods , Education, Medical/methods , Forensic Pathology/education , Photogrammetry/methods , Autopsy/methods , Humans , Hungary , Surveys and Questionnaires
14.
Arq. bras. cardiol ; 115(6): 1178-1179, dez. 2020.
Article in English, Portuguese | WHO COVID, LILACS (Americas) | ID: covidwho-1068340

ABSTRACT

O manejo de dispositivos cardíacos eletrônicos implantáveis de pacientes que evoluem a óbito tem sido motivo de controvérsia. Em nosso meio, não há recomendações uniformes, estando baseadas exclusivamente em protocolos institucionais e em costumes regionais. Quando o cadáver é submetido para cremação, além de outros cuidados, recomenda-se a retirada do dispositivo devido ao risco de explosão e dano do equipamento crematório. Principalmente no contexto da pandemia causada pelo SARS-Cov-2, a orientação e organização de unidades hospitalares e serviços funerários é imprescindível para minimizar o fluxo de pessoas em contato com fluidos corporais de indivíduos falecidos por COVID-19. Nesse sentido, a Sociedade Brasileira de Arritmias Cardíacas elaborou este documento com orientações práticas, tendo como base publicações internacionais e recomendação emitida pelo Conselho Federal de Medicina do Brasil.


The management of cardiac implantable electronic devices after death has become a source of controversy. There are no uniform recommendations for such management in Brazil; practices rely exclusively on institutional protocols and regional custom. When the cadaver is sent for cremation, it is recommended to remove the device due to the risk of explosion and damage to crematorium equipment, in addition to other precautions. Especially in the context of the SARS-CoV-2 pandemic, proper guidance and organization of hospital mortuary facilities and funeral services is essential to minimize the flow of people in contact with bodily fluids from individuals who have died with COVID-19. In this context, the Brazilian Society of Cardiac Arrhythmias has prepared this document with practical guidelines, based on international publications and a recommendation issued by the Brazilian Federal Medical Council.


Subject(s)
Humans , Pacemaker, Artificial , Autopsy/methods , Defibrillators, Implantable , Cardiac Resynchronization Therapy Devices , COVID-19
15.
Pathologica ; 112(2): 64-77, 2020 06.
Article in English | MEDLINE | ID: covidwho-1052586
16.
Hum Pathol ; 109: 59-68, 2021 03.
Article in English | MEDLINE | ID: covidwho-1036692

ABSTRACT

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.


Subject(s)
COVID-19/complications , Liver/virology , SARS-CoV-2/pathogenicity , Thrombosis/pathology , Adult , Aged , Aged, 80 and over , Autopsy/methods , COVID-19/virology , Fatty Liver/pathology , Fatty Liver/virology , Female , Humans , Liver/pathology , Liver Diseases/pathology , Male , Middle Aged , Thrombosis/virology
17.
Curr Opin Pulm Med ; 27(3): 184-192, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1007369

ABSTRACT

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.


Subject(s)
Autopsy/methods , COVID-19/pathology , Lung/pathology , Thrombosis/pathology , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Disease Management , Humans , Immunity , SARS-CoV-2/pathogenicity , Thrombosis/drug therapy , Thrombosis/etiology
18.
Ann Diagn Pathol ; 51: 151682, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-987026

ABSTRACT

Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2 and neuronal NOS plus decreased MFSD2a and SHIP1 proteins. Tail vein injection of the full length S1 spike subunit in mice led to neurologic signs (increased thirst, stressed behavior) not evident in those injected with the S2 subunit. The S1 subunit localized to the endothelia of microvessels in the mice brain and showed co-localization with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons showed increased neuronal NOS and decreased MFSD2a. It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.


Subject(s)
COVID-19/virology , Endothelial Cells/virology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Adult , Aged , Aged, 80 and over , Animals , Autopsy/methods , Disease Models, Animal , Endothelial Cells/metabolism , Female , Humans , Male , Mice , Microvessels/metabolism , Microvessels/virology , Middle Aged , Protein Subunits/metabolism , RNA, Viral/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
20.
Pathobiology ; 88(1): 37-45, 2021.
Article in English | MEDLINE | ID: covidwho-967862

ABSTRACT

Information obtained from autopsies of patients infected with high-risk pathogens is an important pillar in managing a proper response to pandemics, particular in the early phase. This is due to the fact that autopsy allows efficient evaluation of comorbidities for risk assessment, as well as identification of key pathophysiological and molecular mechanisms in organs driving the severity of disease which might be important targets for therapeutic interventions. In the case of patients who have died of infection with unknown pathogens, isolation and culture of pathogens from the affected organs is another important opportunity for a proper response to (re)emerging infectious diseases. However, the situation of COVID-19 demonstrated that there were concerns about performing autopsies because of biosafety risks. In this review we compare requirements for biosafety level 3 (BSL-3) laboratories from the European Commission and the World Health Organization and summarize specific recommendations for postmortem analysis of COVID-19-deceased patients from the Centers for Disease Control and Prevention. Furthermore, we describe in detail a BSL-3 facility with enhanced protection of personnel and an environment that has been designed for performing autopsies, biobanking of collected tissue specimens, and culture of pathogens in cases of high-risk pathogen infections and report on the experience obtained in operating this facility in the context of COVID-19.


Subject(s)
Autopsy , COVID-19/pathology , COVID-19/virology , SARS-CoV-2/pathogenicity , Autopsy/methods , Biological Specimen Banks , Containment of Biohazards , Humans , Laboratories
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