Related Experiment Video
Updated: Dec 12, 2025

Author Spotlight: Deciphering Coagulation Disorders in Traumatic Brain Injury Patients
Published on: August 4, 2023
Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression
Luigi Cipolloni1, Francesco Sessa1, Giuseppe Bertozzi1
1Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.
Insights
Autopsies reveal COVID-19 (coronavirus disease 2019) causes diffuse lung and endothelial damage, potentially explaining its thrombogenicity. Further post-mortem studies are crucial to understand this vascular component.
Area of Science:
- Pathology
- Infectious Diseases
- Public Health
Background:
- COVID-19 (coronavirus disease 2019) poses a significant public health threat.
- Autoptic (post-mortem) studies on COVID-19 are scarce, limiting understanding of pathogenesis.
- Autopsies are vital for determining the precise cause of death.
Purpose of the Study:
- To highlight the importance of autopsies in diagnosing COVID-19 deaths.
- To establish a histological and immunohistochemical protocol for diagnosing COVID-19 fatalities.
- To investigate the role of endothelial damage and thrombogenicity in COVID-19.
Main Methods:
- Histological and immunohistochemical examination of lung tissue from two COVID-19 deceased.
- Comparison with a control case (newborn deceased from pneumonia).
- Analysis of cellular and cytokine expression, ACE2, and Factor VIII (FVIII) positivity.
Main Results:
- COVID-19 infection can induce acute respiratory distress syndrome (ARDS) via diffuse alveolar and endothelial damage.
- Distinct cellular and cytokine expression patterns were observed in anti-COVID-19 antibody-positive cases versus controls.
- Co-localization of COVID-19, ACE2, and FVIII positivity suggests a link between viral infection and endothelial damage.
Conclusions:
- COVID-19, initially viewed as pneumonia, also exhibits characteristics of a vascular disease.
- Widespread endothelial damage may contribute to the thrombogenicity observed in SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection.
- Further post-mortem investigations are essential to elucidate the vascular hypothesis and individual susceptibility in COVID-19.
Abstract:
(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.
Related Concept Videos
Endocarditis II: Clinical Features of Infective Endocarditis
Anticoagulant Drugs: Low-Molecular-Weight Heparins
Venous Thrombosis I: Introduction
Extrinsic and Intrinsic Pathways of Hemostasis
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...

