The pathological autopsy of coronavirus disease 2019 (COVID-2019) in China: a review

Zhou, Baoyong; Zhao, Wei; Feng, Ruixi; Zhang, Xiaohui; Li, Xuemei; Zhou, Yang; Li, Peng; Li, Yixin; Zhang, Jinyan; Luo, Jing; Li, Lingyu; Wu, Jingxian; Yang, Chengliang; Wang, Meijiao; Zhao, Yong; Wang, Kejian; Yu, Hui; Peng, Qiling; Jiang, Ning

doi:10.1093/femspd/ftaa026

Cited by 36 publications

(66 citation statements)

References 24 publications

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“…Lung sections from the two HIS-DRAGA survivors of SARS-CoV-2 infection were further analyzed to characterize pathological changes. As in recent reports based on human autopsies [57][58][59] , the H&E and Mason-trichrome staining of lung sections showed heavy parenchymal infiltrates around the large bronchioles and at peripheral areas of the lungs, as well as hCD45 + cells and human (CD3 + ) T cells dispersed throughout the lung parenchyma, which were more pronounced in the mouse infected with the high dose of virus ( Fig. 5).…”

Section: Sars-cov-2 Infected His-draga Mice Display Human-like Lung Isupporting

confidence: 82%

“…route with non-mouse-adapted SARS-CoV-2, sustaining the infection for at least 14 days, and that they can develop severe human-like lung immunopathology, including T-cell infiltrates, alveolar damage and microthrombi. As in recent analyses of human autopsy samples from COVID-19 patients [57][58][59] , the lung infiltrates of infected DRAGA mice were intra-parenchymal, relatively diffuse, and grouped around terminal bronchioles and at the periphery.…”

Section: Discussionsupporting

confidence: 58%

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A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for COVID-19

Brumeanu

Vir

Shashikumar

et al. 2020

Preprint

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The current SARS-CoV-2 pandemic is accompanied by high morbidity and mortality rates, and there is a compelling need for effective vaccines and therapeutic agents to lessen the severity of COVID-19 disease. Appropriate animal models are essential for testing of vaccines and therapeutics and for mechanistic studies of infection and the host response. The Spike (S) protein of SARS-COV-2 has a high affinity for the human ACE2 receptor, which is expressed on multiple cell types including alveolar epithelial and vascular endothelial cells. Wild-type mice are not susceptible to developing coronavirus-mediated diseases. Accordingly, several human (h)ACE2 transgenic mouse models have been developed for coronavirus research. However, these mice have failed to closely mimic important aspects of the human immunopathological responses to SARS-CoV-2. We report herein that DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL-2R. gammac KO.NOD) mice infused with human hematopoietic stem cells from cord blood reconstitute a fully functional human immune system, as well as engraft human epithelial and endothelial cells, sustain SARS-CoV-2 infection, and develop severe COVID-19-like symptoms. In pilot experiments, infected mice developed parenchymal and epithelial lung infiltrations with granzyme B+ and perforin+ CD8+ T cells and alveolar CD61+ microthrombi, mimicking human immunopathological responses to SARS-CoV-2. We propose the DRAGA mouse as a novel pre-clinical tool for studying COVID-19 immunopathology and human immune responses to SARS-CoV-2, including events leading to the cytokine storm and coagulopathies, as well as for testing of candidate vaccines and therapeutics.

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Section: Sars-cov-2 Infected His-draga Mice Display Human-like Lung Isupporting

confidence: 82%

Section: Discussionsupporting

confidence: 58%

A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for COVID-19

Brumeanu

Vir

Shashikumar

et al. 2020

Preprint

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“…1 Specially, striking lesions observed in vessels, both lymphocytic vasculitis, and the hyalinosis of the arteriolar wall. 27 However, all of them were negative in RT-qPCR tests for SARS-CoV-2 using nasopharyngeal and rectal samples. These results agree with a large-scale study that recently has been shown to assess SARS-CoV-2 infection in 817 companion animals living in northern Italy and neither animals tested positive using RT-qPCR were found.…”

Section: Discussionmentioning

confidence: 96%

Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain

Perisé-Barrios

Tomeo-Martín

Gómez-Ochoa³

et al. 2020

Preprint

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COVID-19 is a zoonotic disease originated by SARS-CoV-2. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Therefore it is necessary to describe the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19. The potential for companion animals contributing to the continued human-to-human disease, infectivity, and community spread is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound study, and computed tomography. Nasopharyngeal and rectal swab were analyzed to detect canine pathogens, including SARS-CoV-2. Twenty healthy dogs living in SARS-CoV-2 positive households were included. Immunoglobulin detection by different immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial pattern, with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. Forty dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Moreover, dogs living in COVID-19 positive households could have been more exposed to be infected during outbreaks.

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“…At the renal level, however, intact glomeruli and acute renal tubular damage have been documented. With anti-COVID-19 antibodies localized only to the renal tubular cells of the tissues infected by immunohistochemical staining [ 70 ]. Additionally, COVID-19 viral nucleocapsid protein antigen, cell apoptosis and proinflammatory cytokine expression have been documented in the spleen and lymph nodes of autopsies of infected subjects.…”

Section: Autopsy Findingsmentioning

confidence: 99%

Clinical-Forensic Autopsy Findings to Defeat COVID-19 Disease: A Literature Review

Sessa

Bertozzi

Cipolloni

et al. 2020

JCM

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The severe acute respiratory syndrome (SARS)-CoV-2 was identified for the first time in China, in December 2019. Confirmed cases of COVID-19 have been reported around the world; indeed, this infection has been declared a pandemic. Consequently, the scientific community is working hard to gain useful information about the history of this virus, its transmission, diagnosis, clinical features, radiological findings, research and development of candidate therapeutics as well as vaccines. This review aims to analyze the diagnostic techniques used to ascertain the COVID-19 infection, critically reviewing positive points and criticism for forensic implications, obviously including autopsy. Finally, this review proposes a practical workflow to be applied in the management of corpses during this outbreak of the COVID-19 infection, which could be useful in cases of future infectious disease emergencies. Analyzing the diagnostic methods, to date, virus nucleic acid RT-PCR represents the standard method used to ascertain the COVID-19 infection in living subjects and corpses, even if this technique has several criticisms: mainly, the staff should be highly specialized, working in high-throughput settings, able to handle high workloads and aware of health risks and the importance of the results. Thus, IgG/IgM serological tests have been developed, overcoming RT-qPCR duration, costs, and management, not requiring highly trained personnel. Nevertheless, serological tests present problems; the WHO recommends the use of these new point-of-care immunodiagnostic tests only in research settings. Furthermore, nothing has yet been published regarding the possibility of applying these methods during post-mortem investigations. In light of this scenario, in this review, we suggest a flow chart for the pathologist called on to ascertain the cause of death of a subject with historical and clinical findings of COVID-19 status or without any anamnestic, diagnostic, or exposure information. Indeed, the literature data confirmed the analytical vulnerabilities of the kits used for laboratory diagnosis of COVID-19, particularly during postmortem examinations. For these reasons, autopsy remains the gold standard method to ascertain the exact cause of death (from or with COVID-19 infection, or other causes), to consequently provide real data for statistical evaluations and to take necessary measures to contain the risks of the infection. Moreover, performing autopsies could provide information on the pathogenesis of the COVID-19 infection with obvious therapeutic implications.

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The pathological autopsy of coronavirus disease 2019 (COVID-2019) in China: a review

Cited by 36 publications

References 24 publications

A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for COVID-19

A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for COVID-19

Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain

Clinical-Forensic Autopsy Findings to Defeat COVID-19 Disease: A Literature Review

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