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Immunomodulatory therapy in helminths: SARS-CoV-2 co-infection
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Resumo(s)
No fim de 2024, quase 5 anos depois do surto inicial, a pandemia de COVID-19
continua alvo de preocupações, particularmente em casos graves onde há uma resposta
imune exacerbada, com a libertação de mediadores pro-inflamatórios como citocinas.
Estas citocinas podem formar um ciclo de feedback positivo, frequentemente referido
como cascata de citocinas que é responsável pelo desenvolvimento de síndrome de
dificuldade respiratória aguda, associado a um mau prognóstico e inclusive morte.
As infeções por helmintas continuam uma preocupação no Sul Global, onde são
consideradas doenças tropicais negligenciadas com elevadas prevalências e se mantêm
uma preocupação devido aos contextos socioeconómicos a que estão associadas. Estas
infeções evoluem para infeções crónicas onde o parasita modula o sistema imunitário
para coexistir com o hospedeiro.
Nesta monografia, o objetivo foi explorar os efeitos imuno-modulatórios das infeções
por helmintas e como estas podem ser benéficas ou prejudiciais para co-infeções por
SARS-CoV-2. Apesar de existirem riscos associados à capacidade de o hospedeiro
combater duas infeções em simultâneo, existem mais benefícios associados à
imunomodulação da resposta por helmintas.
A co-infeção por helmintas pode alterar a típica resposta Th1 à infeção por SARS-CoV
2 para uma resposta reguladora Th2 com foco na redução da inflamação e promoção de
reparação tecidular. Nesta resposta, várias vesiculas extracelulares e outras moléculas
derivadas dos helmintas são libertadas para a corrente sanguínea para ajudar o parasita
a evadir a resposta imunitária, mas podem também reduzir a resposta exacerbada da
cascata de citocinas associada a casos graves de COVID-19.
O próximo passo será o foco na identificação de que moléculas produzidas pelos
helmintas podem ser extraídas ou reproduzidas para uso em formas inovadoras de
terapia imunomoduladora. Este passo é de extrema importância, dado que o uso de
parasitas vivos levantas questões práticas e éticas, além de ser um fator no
desenvolvimento dos riscos associados à co-infeção.
At the end of 2024, nearly five years after the initial outbreak, the COVID-19 pandemic remains of concern, particularly in severe cases where there is an exacerbated immune response with the release of immune mediators like pro-inflammatory cytokines. These cytokines can form a positive feedback loop often called cytokine storm (CS) responsible for the development of acute respiratory distress syndrome (ARDS), associated with poor outcomes and even death. Helminth infections are still a concern in the Global South, where they are considered neglected tropical diseases (NTD) with high prevalences and remain a cause of concern due to their association with poor socio-economic conditions. These infections tend to evolve into chronic infections where the parasite modulates the immune system to be able to coexist with their host. For this work, the objective was to explore the immunoregulatory effects of helminth infections and how these can prove to be beneficial or detrimental to SARS-CoV-2 co infections. Whilst there are some risks related to the ability of the host to fight two infections simultaneously, there may be far more benefits associated with immunomodulation of the response by helminths. Co-infection with helminths can shift from the typical Th1 SARS-CoV-2 immune response towards Th2 and regulatory responses with focus on reducing inflammation and promoting tissue repair. In this response several extracellular vesicles and other helminth derived products are released into the bloodstream to help the helminth evade detection, but they can also help reduce the exacerbated cytokine response often associated with severe cases of COVID-19. The next step now would be to focus on identifying what molecules helminths produce that can be extracted or replicated to use in innovative forms of immunomodulatory therapy. This is of high importance, as the use of live worms raises practical and ethical concerns, as well as being a factor in developing the risks associated with co-infections.
At the end of 2024, nearly five years after the initial outbreak, the COVID-19 pandemic remains of concern, particularly in severe cases where there is an exacerbated immune response with the release of immune mediators like pro-inflammatory cytokines. These cytokines can form a positive feedback loop often called cytokine storm (CS) responsible for the development of acute respiratory distress syndrome (ARDS), associated with poor outcomes and even death. Helminth infections are still a concern in the Global South, where they are considered neglected tropical diseases (NTD) with high prevalences and remain a cause of concern due to their association with poor socio-economic conditions. These infections tend to evolve into chronic infections where the parasite modulates the immune system to be able to coexist with their host. For this work, the objective was to explore the immunoregulatory effects of helminth infections and how these can prove to be beneficial or detrimental to SARS-CoV-2 co infections. Whilst there are some risks related to the ability of the host to fight two infections simultaneously, there may be far more benefits associated with immunomodulation of the response by helminths. Co-infection with helminths can shift from the typical Th1 SARS-CoV-2 immune response towards Th2 and regulatory responses with focus on reducing inflammation and promoting tissue repair. In this response several extracellular vesicles and other helminth derived products are released into the bloodstream to help the helminth evade detection, but they can also help reduce the exacerbated cytokine response often associated with severe cases of COVID-19. The next step now would be to focus on identifying what molecules helminths produce that can be extracted or replicated to use in innovative forms of immunomodulatory therapy. This is of high importance, as the use of live worms raises practical and ethical concerns, as well as being a factor in developing the risks associated with co-infections.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
SARS-CoV-2 Helminth infections Co-infection Immunomodulation Mestrado Integrado - 2024