Whether tobacco smoking affects the occurrence and development of
coronavirus disease 2019 (COVID-19) is still a controversial issue, and potential
biomarkers to predict the adverse outcomes of smoking in the progression of
COVID-19 patients have not yet been elucidated. To further uncover their linkage and explore the effective
biomarkers, three proteomics and metabolomics databases (i.e. smoking status,
COVID-19 status, and basic information of population) from human serum proteomic and metabolomic levels were established by literature search. Bioinformatics analysis was then performed to analyze the interactions of
proteins or metabolites among the above three databases and their biological effects. Potential confounding factors (age, body mass index (BMI), and gender) were controlled to improve the reliability. The obtained data indicated that smoking may increase the relative risk of conversion from non-severe to severe
COVID-19 patients by inducing the dysfunctional immune response. Seven interacting
proteins (C8A, LBP, FCN2, CRP, SAA1, SAA2, and VTN) were found to promote the deterioration of
COVID-19 by stimulating the
complement pathway and macrophage phagocytosis as well as inhibiting the associated negative regulatory pathways, which can be
biomarkers to reflect and predict adverse outcomes in smoking
COVID-19 patients. Three crucial pathways related to immunity and
inflammation, including
tryptophan,
arginine, and
glycerophospholipid metabolism, were considered to affect the effect of smoking on the adverse outcomes of
COVID-19 patients. Our study provides novel evidence and corresponding
biomarkers as potential predictors of severe
disease progression in smoking
COVID-19 patients, which is of great significance for preventing further deterioration in these patients.