scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome

Fähnrich, A.; Reddy, K.D.; Ott, F.; Maluje, Y.; Saurabh, R.; Schaaf, A.; Winkelmann, S.; Voß, B.; Laudien, M.; Bahmer, T.; Heyckendorf, Jan; Brinkmann, F.; Schreiber, S.; Lieb, W.; Weckmann, M.; Busch, H.

doi:10.1101/2024.01.10.574801

Cited by 2 publications

(1 citation statement)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44,45 Others have applied this method to study features of anosmia in olfactory epithelial biopsies or to identify transcriptional features associated with post-acute sequelae using samples collected months after acute SARS-CoV-2 infection. 46,47 A recent human challenge study with the pre-alpha SARS-CoV-2 variant focused on the dynamics of responses in the blood and airway. 48 This unique experimental paradigm enabled the characterization of nasal epithelial and immune cell states during the course of mild infections in unvaccinated individuals.…”

Section: Introductionmentioning

confidence: 99%

Impact of variants and vaccination on nasal immunity across three waves of SARS-CoV-2

Long,

Miao,

Owings

et al. 2024

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 infection and COVID-19 disease vary with respect to viral variant and host vaccination status. However, how vaccines, emergent variants, and their intersection shift host responses in the human nasal mucosa remains uncharacterized. We and others have shown during the first SARS-CoV-2 wave that a muted nasal epithelial interferon response at the site of infection underlies severe COVID-19. We sought to further understand how upper airway cell subsets and states associate with COVID-19 phenotypes across viral variants and vaccination. Here, we integrated new single-cell RNA-sequencing (scRNA-seq) data from nasopharyngeal swabs collected from 67 adult participants during the Delta and Omicron waves with data from 45 participants collected during the original (Ancestral) wave in our prior study. By characterizing detailed cellular states during infection, we identified changes in epithelial and immune cells that are both unique and shared across variants and vaccination status. By defining SARS-CoV-2 RNA+ cells for each variant, we found that Delta samples had a marked increase in the abundance of viral RNA+ cells. Despite this dramatic increase in viral RNA+ cells in Delta cases, the nasal cellular compositions of Delta and Omicron exhibit greater similarity, driven partly by myeloid subsets, than the Ancestral landscapes associated with specialized epithelial subsets. We found that vaccination prior to infection was surprisingly associated with nasal macrophage recruitment and activation rather than adaptive immune cell signatures. While patients with severe disease caused by Ancestral or Delta variants had muted interferon responses, Omicron-infected patients had equivalent interferon responses regardless of disease severity. Our study defines the evolution of cellular targets and signatures of disease severity in the upper respiratory tract across SARS-CoV-2 variants, and suggests that intramuscular vaccines shape myeloid responses in the nasal mucosa upon SARS-CoV-2 infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Impact of variants and vaccination on nasal immunity across three waves of SARS-CoV-2

Long,

Miao,

Owings

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections

Risha,

Reddy,

Nemani

et al. 2024

Allergy

View full text Add to dashboard Cite

BackgroundHumans are subjected to various environmental stressors (bacteria, viruses, pollution) throughout life. As such, an inherent relationship exists between the effect of these exposures with age. The impact of these environmental stressors can manifest through DNA methylation (DNAm). However, whether these epigenetic effects selectively target genes, pathways, and biological regulatory mechanisms remains unclear. Due to the frequency of human rhinovirus (HRV) infections throughout life (particularly in early development), we propose the use of HRV under controlled conditions can model the effect of multiple exposures to environmental stressors.MethodsWe generated a prediction model by combining transcriptome and DNAm datasets from human epithelial cells after repeated HRV infections. We applied a novel experimental statistical design and method to systematically explore the multifaceted experimental space (number of infections, multiplicity of infections and duration). Our model included 35 samples, each characterized by the three parameters defining their infection status.ResultsTrainable genes were defined by a consistent linear directionality in DNAm and gene expression changes with successive infections. We identified 77 trainable genes which could be further explored in future studies. The identified methylation sites were tracked within a pediatric cohort to determine the relative changes in candidate‐trained sites with disease status and age.ConclusionsRepeated viral infections induce an immune training response in bronchial epithelial cells. Training‐sensitive DNAm sites indicate alternate divergent associations in asthma compared to healthy individuals. Our novel model presents a robust tool for identifying trainable genes, providing a foundation for future studies.

show abstract

scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome

Cited by 2 publications

References 74 publications

Impact of variants and vaccination on nasal immunity across three waves of SARS-CoV-2

Impact of variants and vaccination on nasal immunity across three waves of SARS-CoV-2

Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections

Contact Info

Product

Resources

About