Having higher levels of the ACE2 protein in saliva, the one responsible for SARS-CoV-2 penetrating our cells, is related to greater susceptibility to infection by the virus and a higher risk of developing severe covid-19 in unvaccinated patients. This is demonstrated by a study carried out by researchers belonging to the Infectious Diseases area of the CIBER (CIBERINFEC), the Ramón y Cajal Hospital and the Ramón y Cajal Institute for Health Research (IRYCIS), the Pediatrics and Infectious Diseases group of the La Paz Hospital and the of IdiPaz Research and the Catalysis Institute of the Higher Council for Scientific Research (CSIC), which publishes the Journal of Infection.
Angiotensin-converting enzyme 2 (ACE2) is the gate that the SARS-CoV-2 virus uses to enter human cells. This enzyme is expressed in the cell membranes of different tissues of the body, including the pulmonary alveoli and the oral, nasal and nasopharyngeal mucosa, which explains why direct respiratory transmission from person to person is the main means of transmission of SARS-CoV -two.
Different investigations have been endorsing the role of ACE2 in the pathogenesis of covid-19 and, in fact, the increase in the expression of this protein with age could explain the greater severity of the disease in the elderly population, although it has not been confirmed. fully confirmed.
Angiotensin-converting enzyme 2 (ACE2) is the gate that the SARS-CoV-2 virus uses to enter human cells
“In this work we hypothesized that ACE2 activity in saliva would correlate with lower susceptibility to SARS-CoV-2 infection and would explain, at least in part, the formidable clinical phenotype of people with repeated exposures to SARS-CoV-2. high risk to SARS-CoV-2 who were not infected before the implementation of the SARS-CoV-2 vaccine, “he explains. Sergio Serranoresearcher at Hospital Ramón y Cajal- IRYCIS and CIBERINFEC and coordinator of this study.
“Studying children and adults in parallel has provided a very original approach, since since the beginning of the epidemic the lower vulnerability of children to covid-19 has drawn attention and we have been able to confirm that the activity of ACE2 in saliva is lower in children”, explains Talía Sainz, one of the researchers who has led the recruitment of the pediatric cohort.
The team analyzed the expression of ACE2 in saliva in different segments of the population, in a wide range of age and disease status, differentiating between two groups: infected people and those exposed to the virus, but not infected. The cases were collected at the Ramón y Cajal University Hospital, at the La Paz Hospital and at the 12 de Octubre Hospital, between April and June 2020, before the implementation of vaccination. In total, data from 153 patients, 74 adults and 79 children, were included.
Studying children and adults in parallel has provided a very original approach, since since the beginning of the epidemic the lower vulnerability of children to covid-19 has drawn attention and we have been able to confirm that the activity of ACE2 in saliva is lower In children
The results of this work allowed us to observe that there is a correlation between ACE2 activity in saliva and susceptibility to SARS-CoV-2 and the severity of covid-19 in unvaccinated people. Both children and adults with low susceptibility to SARS-Cov-2 infection showed lower levels of ACE2 in saliva.
“In the adult population, an increase in ACE2 activity was detected as the severity of the disease increased,” explains Manuel Ferrer, a co-investigator from the CSIC Institute of Catalysis.
Likewise, “adults who did not become infected despite being highly exposed to the virus had lower levels of ACE2 in saliva than those who were infected.”
In contrast, these differences are not observed in the pediatric population: “In children, a lower ACE2 activity was detected, compared to adults and, in addition, the ACE2 activity in the pediatric population was similar in children susceptible to infection and in those resistant to it”, says Cristina Calvo, a researcher at CIBERINFEC and at the La Paz and IdiPaz University Hospitals.
These findings could inform future strategies to identify people at risk, as well as for the development of therapeutic strategies to reduce both susceptibility and severity of Covid-19.
“The fact that all pediatric cases were asymptomatic or presented mild or resistant infections could support the idea that ACE2 activity correlates with susceptibility to SARS-CoV-2 infection,” explains Calvo.
“These findings could inform future strategies to identify people at risk, as well as for the development of therapeutic strategies to reduce both susceptibility and severity of COVID-19,” the researchers conclude.