ColdZyme® protects airway epithelia from infection with BA.4/5

Zaderer, Viktoria; Dichtl, Stefanie; Rosa, Bellmann-Weiler; Lass-Flörl, Cornelia; Wilfried, Posch; Wilflingseder, Doris

doi:10.1186/s12931-022-02223-2

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…Limitations of this study include that cytokine and C3 expression as well as LDH release were not cross-validated by other methods. However, in earlier reports using SARS-infected tissue culture models, we extensively illustrated the association of these factors (C3, IL-6) with other proinflammatory responses ( 9 , 20 , 21 ). Although the main objective of our study was to compare the pathogenicity between Delta and Omicron variants, our data also revealed differences in viral loads, TEER, LDH and IL-6 expression within Omicron subvariants.…”

Section: Discussionmentioning

confidence: 77%

Omicron subvariants illustrate reduced respiratory tissue penetration, cell damage and inflammatory responses in human airway epithelia

Zaderer,

Abd El Halim,

Wyremblewsky

et al. 2023

Front. Immunol.

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IntroductionTo explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model.MethodsFor this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses.Results and discussionWe observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.

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Section: Discussionmentioning

confidence: 77%

Omicron subvariants illustrate reduced respiratory tissue penetration, cell damage and inflammatory responses in human airway epithelia

Zaderer,

Abd El Halim,

Wyremblewsky

et al. 2023

Front. Immunol.

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“…Inflammatory and cell modulating mechanisms as well as novel therapeutic options mediated at epithelial barrier sites by respiratory viral challenge can be assessed by infection of 3D models of nasal epithelium, upper and lower respiratory tract, or lung. This gives rapid information on the one hand on regional similar-ities/differences and cell types infected; on the other hand, they provide information on the effectiveness of treatment regimen as extensively described by us and others [14,21,26,40,[52][53][54][55][56][57].…”

Section: Infectionsmentioning

confidence: 99%

The breathtaking world of human respiratory in vitro models: Investigating lung diseases and infections in 3D models, organoids, and lung‐on‐chip

Dichtl,

Posch*,

Wilflingseder

2024

Eur J Immunol

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The COVID‐19 pandemic illustrated an urgent need for sophisticated, human tissue models to rapidly test and develop effective treatment options against this newly emerging severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Thus, in particular, the last 3 years faced an extensive boost in respiratory and pulmonary model development. Nowadays, 3D models, organoids and lung‐on‐chip, respiratory models in perfusion, or precision‐cut lung slices are used to study complex research questions in human primary cells. These models provide physiologically relevant systems for studying SARS‐CoV‐2 and, of course, other respiratory pathogens, but they are, too, suited for studying lung pathologies, such as CF, chronic obstructive pulmonary disease, or asthma, in more detail in terms of viral infection. With these models, the cornerstone has been laid for further advancing the organs by, for example, inclusion of several immune cell types or humoral immune components, combination with other organs in microfluidic organ‐on‐chip devices, standardization and harmonization of the devices for reliable and reproducible drug and vaccine testing in high throughput.

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“…Correction: ColdZyme ® protects airway epithelia from infection with BA.4/5 Viktoria Zaderer Following publication of the original article [1], the authors identified an error that the given name and family name of all authors were erroneously transposed. The incorrect citation is: Viktoria Z, Stefanie D, Rosa BW, Cornelia LF, Wilfried P, Doris W.…”

Section: Open Accessmentioning

confidence: 99%

“…Following publication of the original article [ 1 ], the authors identified an error that the given name and family name of all authors were erroneously transposed.…”

mentioning

confidence: 99%