Doutorado em Biotecnologia

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Navegando Doutorado em Biotecnologia por Assunto "Biomarcadores inflamatórios"

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    Patogênese molecular da COVID-19: o envolvimento de fatores genéticos, hemostáticos e imunológicos na evolução de quadros graves, desenvolvimento de coagulopatias e COVID Longa.
    (Universidade Federal do Espírito Santo, 2025-03-21) Silva, Danielle Ribeiro Campos da Silva; Meira, Débora Dummer; https://orcid.org/0000-0002-6092-2459; http://lattes.cnpq.br/7199119599752978; Louro, Iúri Drumond; https://orcid.org/0000-0001-5160-9615; http://lattes.cnpq.br/3817361438227180; https://orcid.org/0009-0004-3821-7376; http://lattes.cnpq.br/8642525842646026; Paula, Flávia de; https://orcid.org/0000-0001-8679-2982; http://lattes.cnpq.br/7913201450663683; Figueiras, Paulo Roberto; https://orcid.org/0000-0002-6068-1982; ; Prezotti, Alessandra Nunes Loureiro; https://orcid.org/0000-0003-1079-7140; http://lattes.cnpq.br/9069306254016368; Pereira, Fausto Edmundo Lima; https://orcid.org/0000-0002-9219-3537; http://lattes.cnpq.br/4065537941002091
    Introduction: The development of the inflammatory process triggered by the SARS-CoV-2 virus leads to abnormal activation of the coagulation system, pathologically manifesting as generalized endothelial dysfunction in small vessels and microthrombosis in the alveolar region. Following the pandemic, persistent symptoms and sequelae are frequently associated with this infection—referred to as “Long COVID”—and generally have a negative impact on individuals’ daily activities. The investigation of coagulation-related markers, cytokines, antiphospholipid antibodies, and genotyping of interleukins and thrombophilia-associated genes that influence hyperinflammation, endothelial dysfunction, and hypoxia is highly relevant for the prognosis of surviving patients. Objective: To investigate molecular and genetic alterations in the hemostatic and inflammatory systems, ABO blood group, and the presence of acquired antibodies in patients who tested positive for COVID-19, as well as the association of these factors with disease severity, potential occurrence of thrombotic complications, and the development of Long COVID. Methods: A total of 226 unvaccinated volunteers (considering two doses) with RT-PCR-confirmed COVID-19 were recruited between November 2020 and December 2021. The cohort was divided into three groups: Mild (60), Moderate (65), and Severe (101), according to WHO guidelines. All participants signed an Informed Consent Form, completed a questionnaire, and had blood samples collected for analysis. The questionnaire assessed relevant preexisting clinical conditions, medical record data, symptoms, and the occurrence of sequelae. Laboratory tests were conducted to assess thrombosis, blood typing, hemostatic/inflammatory biomarkers, and genotyping. Participants whose test results were outside reference ranges were re-evaluated six months later, and after two years, they completed a follow-up questionnaire focused on Long COVID and quality of life. Appropriate statistical tests were used for data analysis. Results: A significant relationship was identified between disease severity and sociodemographic and biomarker data. Statistically significant factors included: age (P age (P<0.0001), lower educational level/ social vulnerability (P<0.0001), ethnicity (P=0.003), overweight (P<0.0001), MTHFR rs1801133 polymorphism (P=0.035), previous cardiovascular disease (P=0.002), diabetes mellitus (DM) (P=0.006), Factor VIII (FVIII) (P=0.046), von Willebrand Factor (vWF) (P=0.0020), and D-dimer (DD) (P<0.0001). After six months, FVIII (P=0.0005), vWF (P=0.0022), and DD (P<0.0001) levels significantly decreased, but only DD returned to normal levels.Sequelae affecting the musculoskeletal, cardiorespiratory, and vascular systems were investigated. Individuals with chronic pulmonary disease (CPD) and DM had higher chances of developing joint pain and myalgia. CPD was also associated with dyspnea and palpitations. Elevated DD levels contributed to palpitations. Prolonged dry cough was associated with lower education and non-white ethnicity. Women were more likely to develop phlebitis. FVIII was associated with a higher risk of cramps, and regular physical activity showed a protective effect against swelling. The EQ-5D-5L questionnaire assessed current quality of life, with the most severely affected participants reporting greater impairment across all measured domains. Conclusion: The findings suggest that endothelial dysfunction is a central factor and may contribute to the development of Long COVID.