The pathophysiologic features of VHF include microvascular instability, increased vascular permeability, and poor hemostasis, albeit the underlying processes differ depending on the virus. Death frequently comes from a process similar to septic shock, where there is insufficient effective intravascular volume circulating, which causes cellular malfunction and multiorgan system failure instead of exsanguination. The virus normally replicates in dendritic cells upon inoculation, then spreads to local lymph nodes and subsequently to a wide range of organs, including the liver, spleen, lymph node, lung, adrenal gland, and endothelium, via lymph and blood monocytes. The specific organs most impacted change depending on the VHF. Interaction of viruses with immune cells, particularly macrophages and endothelial cells, causes the cells to become activated and releases an inflammatory vasoactive process that is compatible with the state known as systemic inflammatory response syndrome. Dysfunction of endothelial cells, platelets, and/or coagulation factors may be present in impaired hemostasis. In certain VHFs, disseminated intravas coagulation (DIC) occurs frequently. The extent of tissue damage varies with VHF and may be caused by either apoptosis or necrosis. Certain VHFs may inhibit cardiotropy, which would worsen organ perfusion. Although not proven, hypothesized causes of vascular collapse include necrosis of the pituitary or adrenal glands. The virus is quickly removed from survivors’ blood, but it can linger for weeks or months in a few immunologically protected areas, including the gonads, central nervous system, and ocular chambers. The last location can lead to the previously described sexual transmission during convalescence. There is a dearth of comprehensive knowledge regarding the pathogenic processes of VHFs. Monocytes, macrophages, dendritic cells, and vascular endothelial cells are important viral target cells. Once infected, these cells can spread to other organs via lymphatics. Studies on experimental viral disease (EVD) have revealed that the viral protein VP35 suppresses the interferon (IFN)-regulatory factor 3, which is essential for the production of IFN α/β and antiviral immune responses. Multiorgan failure, oedema, coagulopathy, shock, tissue necrosis, and endothelial damage are caused by extensive cytokine activation and tissue factor release. Most fatal cases of VHFs do not mount a strong antibody response, which may be owing to virus-induced inhibition of the host adaptive immune response. The pathophysiology of most VHFs appears to be connected to unregulated viremia. During acute sickness, the virus can be detected in a broad range of bodily fluids, including blood, saliva, stool, and breast milk. Usually minor, inflammatory cell infiltration consists of a mixture of neutrophils and mononuclear cells. Nonetheless, the host immune response may be harmful in cases of dengue, yellow fever, and hantavirus infections, in which viremia is typically resolved prior to the most severe stage of the illness. The distinct mechanism known as antibody-mediated enhancement could potentially contribute to the onset of dengue hemorrhagic fever.
Author(s) Details:
Yash Srivastav
Azad Institute of Pharmacy & Research, Lucknow, U.P, India.
Mohd. Faijan Mansoori
Azad Institute of Pharmacy & Research, Lucknow, U.P, India.
Vipin Kumar Pandey
School of Pharmacy, Sangam University, Bhilwara, Rajasthan, India.
Recent Global Research Developments in Pathophysiology and Mechanisms of Viral Hemorrhagic Fevers
Viral hemorrhagic fevers (VHFs) are caused by highly infectious RNA viruses and pose a threat to global public health due to their emergence and re-emergence. These fevers are characterized by an acute febrile syndrome with coagulation abnormalities and generalized hemorrhage, which can lead to life-threatening organ dysfunction [1].
Pathogenesis of VHFs:
VHFs result from abnormal vascular regulation and damage. The molecular mechanisms underlying pathogenesis vary depending on the causative agent, leading to multiorgan failure and death [1].
Clinical manifestations include malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage [2].
Common Features:
VHFs share some clinical features but differ in cell and organ tropism. The causative agents include viruses like Ebola, Lassa, Marburg, and Crimean-Congo hemorrhagic fever (CCHF) virus [1].
Therapeutics and Vaccines:
Efforts are ongoing to develop preventive and therapeutic options for VHFs. These include antiviral drugs, supportive care, and vaccine candidates [1].
For example, CCHF, caused by CCHF virus, is a tickborne disease with varying illness outcomes, from asymptomatic infection to fatal viral hemorrhagic fever [3]
References
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- Basler, C.F. Molecular pathogenesis of viral hemorrhagic fever. Semin Immunopathol 39, 551–561 (2017). https://doi.org/10.1007/s00281-017-0637-x
- Frank MG, Weaver G, Raabe V. Crimean Congo Hemorrhagic Fever Virus for Clinicians—Virology, Pathogenesis, and Pathology. Emerging Infectious Diseases. 2024;30(5):847-853. doi:10.3201/eid3005.231646.
