Numerous studies have substantiated the pivotal role of long non-coding RNAs (lncRNAs) in the progression of non-small cell lung cancer (NSCLC) and the prognosis of afflicted patients. Notably, individuals with NSCLC may exhibit heightened vulnerability to the novel coronavirus disease (COVID-19), resulting in a more unfavorable prognosis subsequent to infection. Nevertheless, the impact of COVID-19-related lncRNAs on NSCLC remains unexplored. The aim of our study was to develop an innovative model that leverages COVID-19-related lncRNAs to optimize the prognosis of NSCLC patients. Pertinent genes and patient data were procured from reputable databases, including TCGA, Finngen, and RGD. Through co-expression analysis, we identified lncRNAs associated with COVID-19. Subsequently, we employed univariate, LASSO, and multivariate COX regression techniques to construct a risk model based on these COVID-19-related lncRNAs. The validity of the risk model was assessed using KM analysis, PCA, and ROC. Furthermore, functional enrichment analysis was conducted to elucidate the functional pathways linked to the identified lncRNAs. Lastly, we performed TME analysis and predicted the drug sensitivity of the model. Based on risk scores, patients were categorized into high- and low-risk subgroups, revealing distinct clinicopathological factors, immune pathways, and chemotherapy sensitivity between the subgroups. Four COVID-19-related lncRNAs (AL161431.1, AC079949.1, AC123595.1, and AC108136.1) were identified as potential candidates for constructing prognostic prediction models for NSCLC. We also observed a positive correlation between risk score and MDSC, exclusion, and CAF. Additionally, two immune pathways associated with high-risk and low-risk subgroups were identified. Our findings further support the association between COVID-19 infection and neuroactive ligand-receptor interaction, as well as steroid metabolism in NSCLC. Moreover, we identified several highly sensitive chemotherapy drugs for NSCLC treatment. The developed model holds significant value in predicting the prognosis of NSCLC patients and guiding treatment decisions.
