question: COVID-19 (Coronavirus Disease 2019) has been an ongoing pandemic, resulting in an increase in people being infected globally Understanding the potential risk of infection for people under different respiratory system conditions is important and will help prevent disease spreading We explored and collected five published and one unpublished single-cell respiratory system tissue transcriptome datasets, including idiopathic pulmonary fibrosis (IPF), aging lungs (mouse origin data), lung cancers, and smoked branchial epithelium, for specifically reanalyzing the ACE2 and TMPRSS2 expression profiles Compared to normal people, we found that smoking and lung cancer increase the risk for COVID-19 infection due to a higher expression of ACE2 and TMPRSS2 in lung cells Aged lung does not show increased risk for infection IPF patients may have a lower risk for original COVID-19 infection due to lower expression in AT2 cells but may have a higher risk for severity due to a broader expression spectrum of TMPRSS2 Further investigation and validation on these cell types are required Nonetheless, this is the first report to predict the risk and potential severity for COVID-19 infection for people with different respiratory system conditions Our analysis is the first systematic description and analysis to illustrate how the underlying respiratory system conditions contribute to a higher infection risk