摘要：SummaryNoncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression ofIL-6,ICAM-1,CXCL-8, andSCGB1A1inflammatory factors;MUC5ACand MUC5Bmucins; andSPDEF,FOXA3, andFOXJ1transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 orLASIwas induced 2-fold in COVID-19 patients, and its expression was directly correlated with viral loads. A SARS-CoV-2-infected 3D-airway model largely recapitulated these clinical findings. RNA microscopy and molecular modeling indicated a possible interaction between viral RNA andLASIlncRNA. Notably, blockingLASIlncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and selectLASI-dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus,LASIlncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response.Graphical abstractDisplay OmittedHighlights•COVID19 airway mucoinflammatory response strongly correlates withLASIlncRNA level•SilencingLASIlncRNA suppresses SARS-CoV-2 viral load and associated inflammation•LASIlncRNA shows a potential direct interaction with SARS-CoV-2 spike viral RNA•Hosts of airway epithelial miRNAs are modulated byLASIto regulate inflammationMolecular biology; Molecular mechanism of gene regulation; Immunology; Virology
