Omicron variant of SARS-CoV-2 exhibits an increased resilience to the antiviral type I interferon response

Shalamova, Lyudmila; Felgenhauer, Ulrike; Schaubmar, Andreas R.; Buettner, Kathrin; Widera, Marek; Ciesek, Sandra; Weber, Friedemann

doi:10.1101/2022.01.20.476754

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…Indeed, there was no notable difference in Omicron RNA titres at 24 hours post-infection in adult vs pediatric NECs. These data may provide preliminary evidence that the Omicron variant, at least to some extent, is able to evade aspects of the pediatric innate immune response, as has previously been demonstrated [53]. Whether this is sufficient to result in an increased number of pediatric infections during the Omicron wave [54,55], or whether other factors are more important, remains to be determined.…”

Section: Discussionmentioning

confidence: 54%

Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells

Zhu

Chew

et al. 2021

Preprint

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Rationale: Young children (typically those <10 years old) are less susceptible to SARS-CoV-2 infection and symptoms compared to adults. However, the mechanisms that underlie these age-dependent differences remain to be determined and could inform future therapeutics for adults. Objective: To contrast the infection dynamics of SARS-CoV-2 in primary nasal epithelial cells from adults and children. Methods: Viral replication was quantified by plaque assay. The cellular transcriptome of infected and uninfected cells was assessed by RNA-seq. ACE2 and TMPRSS2 protein expression were quantified by Western Blot Measurements and Main Results: We report significantly higher SARS-CoV-2 replication in adult compared to pediatric nasal epithelial cells. This was restricted to SARS-CoV-2 infection, as the same phenomenon was not observed with influenza virus infection. The differentiational SARS-CoV-2 replication dynamics were associated with an elevated type I and III interferon response, and a more pronounced inflammatory response in pediatric cells. No significant difference between the two age groups was observed in the protein levels of ACE2 and TMPRSS2. Conclusions: Our data suggest that the innate immune response of pediatric nasal epithelial cells, and not differential receptor expression, may contribute to the reported reduced SARS-COV-2 infection and symptoms reported amongst children.

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Section: Discussionmentioning

confidence: 54%

Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells

Zhu

Chew

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…1A ). This can be inefficient and restricts the virus to the slower endocytic entry route, in which the virus relies on pH-dependent cathepsins and may be more susceptible to restriction by certain innate immune factors, e.g., interferon-stimulated genes ( 40 , 41 ) such as IFITMs, which rigidify cell membranes to prevent fusion ( 42 , 43 ). Proprotein convertase (furin) preprocessing at the S1/S2 site leads to a more labile and fusogenic, but less stable, spike protein ( 32 ).…”

Section: Coronavirus Entrymentioning

confidence: 99%