Pathologists in pursuit of the COVID-19 culprit

Yi, Eunhee; Cecchini, Matthew J.; Bois, Melanie C.

doi:10.1016/s1473-3099(20)30449-7

Cited by 7 publications

(7 citation statements)

References 8 publications

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“…These results are associated with an inflammatory infiltrate, consisting of alveolar macrophages and interstitial lymphocytes. The ante-mortem involvement of both established DAD and disseminated intravascular coagulation (DIC) models may explain the serious hypoxemia that characterizes ARDS in subjects with COVID-19 [ 46 ]. Finally, the FVIII-von Willebrand Factor (vWF) complex is another prothrombotic unit responsible for the adhesion of platelets to subendothelial structures, released by endothelial cells when injured, in association with severe endothelial dysfunction; thus, it has been suggested as a biomarker of endothelial dysfunction, which is largely involved in COVID-19 pathogenesis [ 47 , 48 , 49 , 50 , 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression

et al. 2020

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(1) Background: The current outbreak of COVID-19 infection is an ongoing challenge and a major threat to public health that requires surveillance, prompt diagnosis, as well as research efforts to understand the viral pathogenesis. Despite this, to date, very few studies have been performed concerning autoptic specimens. Therefore, this study aimed: (i) to reiterate the importance of the autoptic examination, the only method able to precisely define the cause of death; (ii) to provide a complete post-mortem histological and immunohistochemical investigation pattern capable of diagnosing death from COVID-19 infection. (2) Methods: In this paper, the lung examination of two subjects who died from COVID-19 are discussed, comparing the obtained data with those of the control, a newborn who died from pneumonia in the same pandemic period. (3) Results: The results of the present study suggest that COVID-19 infection can cause different forms of acute respiratory distress syndrome (ARDS), due to diffuse alveolar damage and diffuse endothelial damage. Nevertheless, different patterns of cellular and cytokine expression are associated with anti-COVID-19 antibody positivity, compared to the control case. Moreover, in both case studies, it is interesting to note that COVID-19, ACE2 and FVIII positivity was detected in the same fields. (4) Conclusions: COVID-19 infection has been initially classified as exclusively interstitial pneumonia with varying degrees of severity. Subsequently, vascular biomarkers showed that it can also be considered a vascular disease. The data on Factor VIII discussed in this paper, although preliminary and limited in number, seem to suggest that the thrombogenicity of Sars-CoV2 infection might be linked to widespread endothelial damage. In this way, it would be very important to investigate the pro-coagulative substrate both in all subjects who died and in COVID-19 survivors. This is because it may be hypothesized that the different patterns with which the pathology is expressed could depend on different individual susceptibility to infection or a different personal genetic-clinical background. In light of these findings, it would be important to perform more post-mortem investigations in order to clarify all aspects of the vascular hypothesis in the COVID-19 infection.

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Section: Discussionmentioning

confidence: 99%

Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression

et al. 2020

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“…These findings are associated with an inflammatory infiltrate, consisting of alveolar macrophages and interstitial lymphocytes. The involvement of both ascertained DAD and suggested ante-mortem disseminated intravascular coagulation patterns could explain the severe hypoxemia that characterizes ARDS in subjects with COVID-19 [ 79 ].…”

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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“…However, our study illustrates that autopsies during the COVID-19 era are possible to conduct on SARS-CoV-2 infected subjects in Zambia. There is a need to revive clinical and research autopsies througout sub-Saharan African countries ( Mawalla, 2020 , Mucheleng’anga and Himwaze, 2020 , Bruce-Brand et al, 2020 , Mudenda et al, 2020 , Rampatige and Gilks, 2015 , Barth et al, 2020 , Yi et al, 2020 ) to add to the provisional information provided by our study. Further autopsies with accurate data are required to conjure a more comprehensive picture of the pathogenesis and impact of COVID-19 in SSA.…”

Section: Discussionmentioning

confidence: 99%

Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series

Himwaze¹,

Telendiy²,

Maate³

et al. 2021

International Journal of Infectious Diseases

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Background Since information on the pathology of COVID-19 from sub-Saharan Africa (SSA) remains scarce, the objective of our study was to define the gross pathology and histological features of COVID-19. We report data from 29 whole-body autopsies of COVID-19 deaths occurring in hospitals in Lusaka, Zambia - the first large autopsy case series from Africa. Methods We performed a descriptive post-mortem examination study of inpatient COVID-19 related deaths at two hospitals in Lusaka, Zambia. Whole-body autopsies were conducted according to Standard Operating Procedures. Gross and histopathological examinations of all organs were performed. Patient demographics, history, co-morbidities, autopsy gross and microscopic findings, and cause(s) of death were recorded and analyzed using STATA version 14. Variables were grouped and presented as frequencies and percentages. Findings Autopsies were performed on 29 decedents (mean age = 44 ± 15.8years; age range = 19-82; 17/29 [58.8%] males). 22/29 [75.9%] cases were <55 years of age. A spectrum of pathological manifestations of COVID-19 were seen in all organs. The commonest causes of death were pulmonary thromboembolism (13/29, 45%), Diffuse Alveolar Damage (9/29, 31%), and COVID-19 pneumonia (7/29, 25%). 22/29 (76%) had co-morbidities. Common co-morbidities included HIV (8/29, 28%), Hypertension (6/29, 20%) Tuberculosis (3/29, 10%), Diabetes (3/29, 10%). Conclusions A spectrum of gross anatomical and histopathological findings are seen in COVID-19 deaths in hospitalized decedents. These appear broadly similar to those reported from China, Europe and USA. Differences include a younger age group, and co-morbidities of HIV and TB co-infection which require further investigation.

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Pathologists in pursuit of the COVID-19 culprit

Cited by 7 publications

References 8 publications

Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression

Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression

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

Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series

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