Ectodomain shedding of proteins important for SARS-CoV-2 pathogenesis in plasma of tobacco cigarette smokers compared to electronic cigarette vapers: a cross-sectional study

Theodoros Kelesidis, Madhav Sharma, Sandro Satta, Elizabeth Tran, Rajat Gupta, Jesus A. Araujo, Holly R. Middlekauff

The impact of tobacco cigarette (TCIG) smoking and electronic cigarette (ECIG) vaping on the risk of development of severe COVID-19 is controversial. The present study investigated levels of proteins important for SARS-CoV-2 pathogenesis present in plasma because of ectodomain shedding in smokers, ECIG vapers, and non-smokers (NSs). Protein levels of soluble angiotensin-converting enzyme 2 (ACE2), angiotensin (Ang) II (the ligand of ACE2), Ang 1-7 (the main peptide generated from Ang II by ACE2 activity), furin (a protease that increases the affinity of the SARS-CoV-2 spike protein for ACE2), and products of ADAM17 shedding activity that predict morbidity in COVID-19 (IL-6/IL-6R alpha (IL-6/IL-6Rα) complex, soluble CD163 (sCD163), L-selectin) were determined in plasma from 45 NSs, 30 ECIG vapers, and 29 TCIG smokers using ELISA. Baseline characteristics of study participants did not differ among groups. TCIG smokers had increased sCD163, L-selectin compared to NSs and ECIG vapers (p < 0.001 for all comparisons). ECIG vapers had higher plasma furin compared to both NSs (p < 0.001) and TCIG smokers (p < 0.05). ECIG vaping and TCIG smoking did not impact plasma ACE2, Ang 1-7, Ang II, and IL-6 levels compared to NSs (p > 0.1 for all comparisons). Further studies are needed to determine if increased furin activity and ADAM17 shedding activity that is associated with increased plasma levels of sCD163 and L-selectin in healthy young TCIG smokers may contribute to the future development of severe COVID-19 and cardiovascular complications of post-acute COVID-19 syndrome.