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Plasmodium berghei/SARS-CoV-2 co-infection phenotype in murine models
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Resumo(s)
Coronavirus disease 2019 (COVID-19) and malaria, caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium parasites, respectively, share geographical
distribution, in regions where the latter disease is endemic. Because of this geographic overlap, coinfection cases have emerged, albeit with variable clinical presentations, ranging from faster clinical
recovery to worse health outcomes. Given the current epidemiologic status of both diseases, the
occurrence of co-infections between SARS-CoV-2 and Plasmodium is likely to persist. Thus far,
epidemiologic studies and case reports have yielded insufficient data on the reciprocal impact of the two
pathogens on either infection and related diseases. As such, an experimental approach of this coinfection is critical for the understanding of how these pathogens interact with each other and the impact
of this interaction on the progression of either disease. We established a unique and innovative coinfection model to address this issue experimentally for the first time, employing either transgenic mice
expressing SARS-CoV-2’s human receptor for cell invasion – the human angiotensin-converting
enzyme 2 (hACE2) – or wild-type mice in combination with human- and mouse-infective variants of
SARS-CoV-2, respectively, and the rodent malaria parasite, P. berghei. Our results demonstrate for the
first time that an ongoing SARS-CoV-2 infection impacts the outcomes of a subsequent Plasmodium
infection. Our data shows that a primary infection by a viral variant that causes a severe disease
phenotype leads to an exacerbated anti-viral immune response that markedly impairs a subsequent liver
infection by the malaria parasite. Additionally, we demonstrate that a primary infection by a viral variant
that causes an attenuated disease phenotype reduces malaria severity in mice subsequently infected with
P. berghei, partially protecting these animals from experimental cerebral malaria and increasing their
survival. Our results have unveiled a hitherto unknown virus-parasite interaction that could have
important epidemiological and clinical repercussions in malaria-endemic regions, particularly regarding
the management and control of the diseases caused by both pathogens. This work paves the way for the
development of other models of co-infection between Plasmodium and respiratory viruses in relevant in
vivo models of disease and we anticipate that it will serve as a steppingstone for further research on coinfections, thus filling an important knowledge gap regarding complex disease presentations.
Descrição
Tese de mestrado, Biologia Molecular e Genética , 2023, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Malária COVID-19 coinfeção Plasmodium SARS-CoV-2 Teses de mestrado - 2023