Molecular Analysis of Hot-Spot Regions of ACE2 and TMPRSS2 in SARS-CoV-2 “Invulnerable” Individuals

Background Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical variability, ranging from acute illness that may require hospitalization and intensive care unit management to mild and even asymptomatic disease. A more exciting phenomenon is the presence of individuals who came into close contact with COVID-19 patients without prophylaxis but were never infected by SARS-CoV-2, even as an asymptomatic disease. Aims We describe four such “invulnerable” individuals and explore if they carry genetic defects in hot-spot regions of ACE2 and TMPRSS2 genes, which are responsible for virus entry into the host cells. Materials and methods Anti-S humoral and cellular immune responses were evaluated in the study participants through chemiluminescent microparticle immunoassay (CMIA) and enzyme-linked immunosorbent assay (ELISA) and interferon (IFN-γ) secretion measurement, respectively. Moreover, the hot-spot locations of ACE2 and TMPRSS2 were analyzed by polymerase chain reaction (PCR) sequencing in order to investigate potential genetic defects. Results No pathogenic genetic defects in ACE2 and TMPRSS2 were identified in the study participants. However, a functional polymorphism (rs12329760) located in exon 6 of the TMPRSS2 gene was detected in two of the four participants. In addition, it is worth noting that two individuals displayed adequate humoral and cellular immune responses after COVID-19 vaccination several months after their initial exposure to SARS-CoV-2. Conclusions We suggest that ACE2 and TMPRSS2 genes are not responsible for the “invulnerable” phenotype against COVID-19.