An examination of the samples revealed that, in general, patients who died exhibited an increased amount of blood and an accumulation of liquid in the lungs, heart, liver, spleen, kidneys, and brain, although they did not have a greater concentration of the virus than the survivors did, nor had they been infected with a more aggressive strain of CHIKV.<\/p>\n
The blood from patients who died also contained significantly higher levels of two types of chemical communicators than in patients from the other groups: proinflammatory cytokines, proteins that coordinate the immune defense, and chemokines, a class of cytokines responsible for attracting cells from the immune system to the sites of inflammation. Associated with symptoms of hyperinflammation, these molecules alter the permeability of the internal wall of the blood vessels, allowing the liquid portion of the blood to escape and accumulate within the tissues. These molecules also facilitate the penetration of defense cells in tissues; while attempting to eliminate the virus, defense cells can sometimes destroy healthy cells.<\/p>\n
![\"\"](\"https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2025\/01\/rpf-chikungunya-cerebro-340.jpg\")
De souza, w. m. cell host & microbe<\/strong>. 2024\u2009<\/span>Intact cells from the lining of blood vessels of the brain (left<\/em>), compared to CHIKV-infected cells that have been destroyed (right, in red<\/em>)De souza, w. m. cell host & microbe<\/strong>. 2024\u2009<\/span><\/p><\/div>\n Among the patients who died, the presence of defense cells was observed in the heart, liver, kidneys, and, most intriguingly to researchers, the brain. The blood vessels that supply the central nervous system have a unique and highly selective lining called the blood-brain barrier. This barrier allows the passage of oxygen, nutrients, and some rare defense cells from the blood to the brain but usually prevents the entry of pathogens. Souza and colleagues reported that the virus was detected in the cerebrospinal fluid, the liquid that surrounds the brain and other organs of the central nervous system, in all patients who died, which indicated that CHIKV had crossed the blood-brain barrier. The virus was detected in 13% of the brain samples, 20% of the heart and kidney samples, 28% of the liver samples, 44% of the lung samples, and 52% of the spleen samples from patients who died.<\/p>\n All of the infected people exhibited metabolic dysregulation, which was more intense in patients who died than in the survivors. This dysregulation affects the integrity and permeability of the blood-brain barrier, potentially facilitating the invasion of the brain by pathogens.<\/p>\n However, metabolic dysregulation was not the only mechanism involved. Laboratory tests performed by the group revealed that the virus was also capable of infecting monocytes, which are defense cells that naturally cross the blood\u2013brain barrier, using them as a type of Trojan horse. \u201cIt hides inside the monocytes and, therefore, reaches the brain,\u201d explains pharmacist Shirlene de Lima of the Central Laboratory of Public Health of the State of Cear\u00e1 (LACEN\/CE), one of the lead authors of the study.<\/p>\n By analyzing the affected organs and tissues, researchers identified extensive damage in the brain, including bleeding and cell death. They still do not know which of the factors\u2013hemodynamic imbalance, exacerbated inflammation, or infection of the central nervous system\u2013is the most important factor indicating a fatal outcome. \u201cWe need more studies to understand the contribution of each of these problems and why they affect some people more than others,\u201d says Lima. \u201cThis knowledge is fundamental for developing better treatment approaches.\u201d Currently, therapy consists of the administration of analgesics, antipyretics, and anti-inflammatories to alleviate symptoms.<\/p>\n \u201cThe study provides relevant information mainly about the behavior of the chemokines and about molecular signatures associated with the patients who died,\u201d states infectologist Julio Croda of the Oswaldo Cruz Foundation in Mato Grosso do Sul (FIOCRUZ-MS), who did not take part in the study. \u201cThe infiltration of the infected monocytes in the brain and its effect is a new finding. Now we need larger studies, with people of different ethnicities, ages, and genders, to validate these conclusions.\u201d<\/p>\n Until a more effective treatment is found, hope rests on the development of a vaccine. In November 2023, the Food and Drug Administration (FDA), the agency that regulates food and drugs in the USA, approved the use of Ixchiq, a vaccine based on the weakened virus developed by the Franco-Austrian pharmaceutical company Valneva, for adults. In Brazil, the company has a partnership with the Butantan Institute, which is currently testing the composition in phase 3 clinical trials in adolescents before submitting a request for approval by the Brazilian Health Regulatory Agency (ANVISA).<\/p>\n Projects<\/strong>
\n1.<\/strong>\u00a0Multiomic approaches to the study of Chikungunya disease (n\u00ba 19\/24251-9<\/a>)<\/u>;\u00a0Grant Mechanism\u00a0<\/strong>Postdoctoral Fellowship Abroad;\u00a0Supervisor\u00a0<\/strong>Luiz Tadeu Moraes Figueiredo (USP);\u00a0Beneficiary\u00a0<\/strong>William Marciel de Souza;\u00a0Investment\u00a0<\/strong>R$301,943.10.
\n2.<\/strong>\u00a0Characterization, genomics, and diagnosis of viruses with public health importance in Brazil by high-performance sequencing (n\u00ba 17\/13981-0<\/u><\/a>);\u00a0Grant Mechanism<\/strong>\u00a0Postdoctoral Fellowship;\u00a0Supervisor<\/strong>\u00a0Luiz Tadeu Moraes Figueiredo (USP);\u00a0Beneficiary\u00a0<\/strong>William Marciel de Souza;\u00a0Investment<\/strong>\u00a0R$303,193.93.<\/p>\n