Infección por SARS-CoV-2 en población pediátrica: dinámica de la respuesta inmune en la patogenia y resolución de la enfermedad
More than 700 million people have become infected with SARS-CoV-2 since March 2020, and the incidence of paediatric COVID-19 represents 2 to 7% of confirmed cases. Children often experience asymptomatic or mild forms of the disease, but adults can develop severe forms, showing signs of a dysregulate...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2024
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_7888 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_7888.dir/7888.PDF |
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| Sumario: | More than 700 million people have become infected with SARS-CoV-2 since March 2020, and the incidence of paediatric COVID-19 represents 2 to 7% of confirmed cases. Children often experience asymptomatic or mild forms of the disease, but adults can develop severe forms, showing signs of a dysregulated immune response. In the first part of this work, we characterized the properties of neutrophils in children with acute COVID-19, highlighting an atypical phenotype with a decrease in the adhesion molecules CD11b, CD66b, and CD62L, along with an increase in the expression of the activation markers CD64, HLA-DR, and PECAM-1, as well as the inhibitory receptors LAIR-1 and PD-L1. On the other hand, neutrophils from children with MIS-C display similarities to those observed in adults with severe COVID-19. Finally, we propose the CD64 receptor as a biomarker to predict disease severity. These data suggest that neutrophils in children with acute COVID-19 have a reduced capacity to migrate, providing protection against lung damage. The second part addresses a different aspect of the immune response to SARS-CoV-2. We focussed on defining the quality and duration of the antibody response generated by natural immunity and hybrid immunity. We found that children and adults exhibit a different kinetics of antibody production, with children having higher titres of neutralizing antibodies beyond one-year post-infection. Additionally, circulating antibodies from children infected with variants prior to Omicron can neutralize it, indicating that this variant does not completely evade the immune response. Furthermore, both the BBIBP-CorV vaccine and mRNA vaccines enhanced the antibody response in previously infected children who received 2 vaccine doses. The evasion capability of Omicron becomes more significant in immunocompromised patients, who show a lower response of neutralizing antibodies compared to healthy children, beyond 10 months post-vaccination, with a similar T cell-mediated response. Our data demonstrate the crucial relevance of vaccination against SARS-CoV-2 in children. Finally, we studied the long-term consequences of having suffered COVID-19. We found that 23% of the children had sequelae for more than 3 months after SARS-CoV-2 infection, highlighting age, the presence of symptoms during the acute phase of COVID-19, and history of diabetes, respiratory and renal diseases as risk factors for the development of Long COVID. Considering the results, they underscore the need to understand the dynamics of the immune response in children in health and disease, and to ensure equitable access to health in terms of vaccination and medical care. |
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