Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels

Abstract

Background Angiotensin-converting enzyme 2 (ACE2) is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19. Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2). Transcriptomic studies showed that children display lower ACE2 than adults, though gene expression levels do not always correlate with protein levels. We investigated the effect of age on ACE2 and TMPRSS2 protein expression in alveolar type II (AT2) cells in the lungs of children compared to adults. We also analysed the ratio of Ang-(1–7) to Ang II as a surrogate marker of ACE2 activity in the subjects’ lung parenchyma. Methods Ang II and Ang-(1–7) levels and ACE2 and TMPRSS2 protein expression were measured by radioimmunoassay and immunohistochemistry, respectively. Results The amount of ACE2-expressing AT2 cells and ACE2 protein content were lower in children than in adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells. Children presented lower Ang-(1–7)/Ang II ratio than adult suggesting lower ACE2 activity in children. TMPRSS2 protein expression was not influenced by age. Conclusions These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection. Category of study Clinical original research Impact Children display lower ACE2 protein content and activity compared to adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells TMPRSS2 protein expression was not influenced by age. These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection.

Angiotensin-Converting Enzyme 2 Expression and Severity of SARS-CoV-2 Infection

“…Non-ventilated individuals did not demonstrate these changes in type II pneumocytes and experienced no such age-related increase in expression [ 30 ]. Silva et al demonstrated similar findings in type II pneumocytes and consequently identified that angiotensin II levels in children were higher than those in adults [ 31 ]. Ang-(1–7)/Ang II ratios served as surrogate markers for ACE2 activity in this study and were higher in adults [ 31 ].…”

“…Silva et al demonstrated similar findings in type II pneumocytes and consequently identified that angiotensin II levels in children were higher than those in adults [ 31 ]. Ang-(1–7)/Ang II ratios served as surrogate markers for ACE2 activity in this study and were higher in adults [ 31 ].…”

Aging shapes infection profiles of influenza A virus and SARS-CoV-2 in human lung slices

“…Whereas in some studies no differences in SARS-CoV-2 RNA loads between children and adults were found (75, 76), others reported slightly lower viral RNA loads in children (77, 78). ACE2 expression was shown to be age-dependent in the nasal epithelium (79) as well as in alveolar type 2 cells (80), with lower expression in children compared to adults. However, our study focused on lung tissue from adult donors and didn’t include younger adults and children.…”

The logic of coronavirus infection: revealing the heterogeneity of disease progression and treatment outcomes in COVID patients

“…For example, clinical records showed that people in younger age are less likely to develop severe symptoms when infected 5,49 . This may be partially due to the fact that pulmonary epthelia in younger people express less viral receptors [50][51][52] . Blocking these receptors can achieve much lower infection rate 40,53,54 .…”