Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection

Choi, Chang‐Yong; Gadhave, Kundlik; Villano, Jason; Pekosz, Andrew; Mao, Xiaobo; Jia, Hongpeng

doi:10.1002/jmv.29349

Cited by 1 publication

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References 60 publications

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“…A limitation of this study is that we have not investigated the responses over the long-term, with a role for iron status in increasing the severity of long-COVID suggested by several studies [12, 19, 173]. However, whether mouse models [174] can faithfully recapitulate pathological or immunopathological features of human long-COVID remains to be established [175], with underlying co-morbidities [176] clearly absent in genetically identical, specific pathogen free, laboratory mice. We have also not provided insights into the sizable range of co-morbidities that can give rise to anemia or iron overload [53, 177, 178], and how these would affect COVID-19; however, this would constitute a considerable undertaking.…”

Section: Discussionmentioning

confidence: 99%

The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease

Carolin,

Frazer,

Yan

et al. 2024

Preprint

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The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Here we generate iron deficient and iron loaded C57BL/6J mice by feeding low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary omicron XXB SARS-CoV-2 isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations.Author summaryA diet deficient in iron can lead to anemia, a widespread problem worldwide. A diet with excessive iron is less common, but can be associated with excessive consumption of iron supplements. We investigate herein using a mouse model, whether low or high iron diets predispose to detrimental outcomes in the lungs after infection with SARS-CoV-2. A considerable literature suggests iron dysregulation would promote infection and inflammation. However, we found, although inflammatory responses showed modest modulations, viral loads were unaffected or slightly reduced, and lung histopathology was either unaffected or indicated slightly less severe disease. These findings do not support a view that low or high iron diets represent comorbidities predisposing to overt detrimental outcomes for acute COVID-19 lung disease.

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