In a recent study published in the journal Internal and Emergency Medicine, researchers determined whether infection with monkeypox (MPX) affected the hemostatic system as seen in coronavirus disease 2019 (COVID-19).
Study: Monkeypox outbreak: after COVID-19, another challenge for the hemostatic system? Image credit: Phonlamai Photo/Shutterstock
The scientific community’s understanding of the framework associating viral infection with endothelial inflammation, prothrombotic transformation, and barrier failure has been greatly enhanced by analysis of the pathogenetic mechanisms underlying COVID-19-associated coagulopathy (CAC ). In addition, the public was made aware of the potential thrombotic and hemorrhagic risks associated with adenovirus as vaccine and gene therapy vectors due to vaccine-induced thrombosis and thrombocytopenia (VIT) syndrome reported in some recipients of ChAdOx1 nCoV-19 and Ad26.
Pathology of monkeypox infection
The predominant pathologic manifestation of MPX virus infection is epithelial cell damage, manifested as globus degeneration, intracytoplasmic eosinophilic inclusion, keratinocyte hyperplasia, and necrosis. There is also vasculitis and lymphocytic inflammation of the dermis. It should be noted that there are no data on the histology of individuals who have succumbed to MPX infection.
Fever is often the first sign of illness, followed by the appearance of many papular, ulcerative, and vesiculopustular lesions on the face and body, along with lymphadenopathy. Most of the time, the monkeypox infection was self-limiting and lasted two to four weeks. However, complications such as encephalitis, keratitis, pneumonitis and secondary bacterial infections can occur, leading to a mortality rate of 1% to 11%, mainly in low-income countries. Notably, the viral genome sequenced from several nations closely resembled the indigenous West African strain, which has a mortality rate of 1%, which is about ten times lower compared to the rate observed for the Central African clade.
Impact of MPX infection
Due to their ability to avoid detection and targeting by the host immune system, phleboviruses are predicted to have a less significant effect on the thromboinflammation process. MPX virus infection of primary fibroblasts in vitro results in inhibition of interferon-stimulated gene (ISG) and CC motif chemokine ligand 5 (CCL-5) expression, tumor necrosis factor-alpha (TNF -alpha), interleukin (IL)-1 alpha and beta, and IL-6, all factors that are involved in the cytokine storm experienced in COVID-19.
Given these clinical and pathophysiological considerations, the hemostatic system is expected to play little or negligible role in monkeypox infection, as evidenced by the absence of thrombotic or hemorrhagic consequences in these patients. Because the deoxyribonucleic acid (DNA) virus Variola major, the causative pathogen of smallpox (SPX), and monkeypox virus are relatively distant relatives, minor consequences of monkeypox infections may be short duration
Clinical manifestations of MPX
Notably, a study by Schultz and colleagues in 2009 identified an animal model of MPX infection that had characteristics more similar to the hemorrhagic SPX subtype and produced more severe disease than previous rodent models associated with the human MPX disease. Although substantial hepatic necrosis with endothelial damage and loss of coagulation factors in affected organs have been theorized to play a role in multiorgan hemorrhage, the mechanism of such a bleeding course has not been identified. serious Additionally, a hemorrhagic rash, thrombocytopenia, and mortality were associated with a low-dose SPX and MPX model in marmosets.
According to one theory, when dendritic cells and macrophages become infected with viral hemorrhagic fever, they cannot produce enough type I interferon (IFN), causing the lymphocytes to undergo cell death. Increased vascular permeability results from the disruption of inappropriate dendritic cell function of the innate immune system, which is exacerbated by the unrestrained release of cytokines from infected macrophages. In addition, replicated viruses spread throughout the body and cause various systemic reactions, including visceral parenchymal cell dysfunction, platelet impairment, and coagulopathy, which contribute to disseminated intravascular coagulation and uncontrolled bleeding.
Overall, the results of the study suggested that the MPX outbreak is unlikely to have a significant effect on hemostatic diseases, especially bleeding diseases. Although new developments in the pathophysiology of virus-induced thromboinflammation should be constantly considered, the intimate connection between hemostasis, viruses, and inflammation should not be overlooked.