Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection

• Published in: medRxiv : the preprint server for health sciences
• Main Authors: Devadoss, Dinesh, Acharya, Arpan, Manevski, Marko, Pandey, Kabita, Borchert, Glen M, Nair, Madhavan, Mirsaeidi, Mehdi, Byrareddy, Siddappa N, Chand, Hitendra S
• Format: Journal Article
• Language: English
• Published: United States 18.05.2021
• DOI: 10.1101/2021.05.13.21257152

Respiratory epithelial cells are the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the 3D human airway tissue model to evaluate innate epithelial cell responses to SARS-CoV-2 infection. A SARS-CoV-2 clinical isolate productively infected the 3D-airway model with a time-dependent increase in viral load (VL) and concurrent upregulation of airway immunomodulatory factors ( , and ) and respiratory mucins ( , and , and differential modulation of select long noncoding RNAs (lncRNAs i.e., , and ). Next, we examined these immunomodulators in the COVID-19 patient nasopharyngeal swab samples collected from subjects with high- or low-VLs (∼100-fold difference). As compared to low-VL, high-VL patients had prominent mucoinflammatory signature with elevated expression of , and . Interestingly, , and lncRNA expressions were also markedly elevated in high-VL patients with no change in expression. In addition, dual-staining of and SARS-CoV-2 nucleocapsid RNA showed predominantly nuclear/perinuclear localization at 24 hpi in 3D-airway model as well as in high-VL COVID-19 patient nasopharyngeal cells, which exhibited high MUC5AC immunopositivity. Collectively, these findings suggest SARS-CoV-2 induced lncRNAs may play a role in acute mucoinflammatory response observed in symptomatic COVID-19 patients.