The objective of this review of literature, is to show if the deficiency of ACE2 is a factor who provide this protection for children from Sars-Cov-2. Three major findings were found after researching. First, The minority of cases in children category. Secondly, ACE2 resulting penetration in cells after the interaction with virus. And third, a poor presence of ACE2 in lungs children.
Apart from the limited number of pediatric cases during the outbreak, the assessment of disease and severity was also significantly less dangerous than in adults. After microbiological confirmation that the person was positive, many studies have shown that clinically, children (age < 18) are more tolerant than adults: clinical signs with mild evolution such as fever, cough, and rhinorrhea. In addition, although radiological examinations are not highly recommended in pediatrics, studies found that the pulmonary lesions shown by chest CT were weaker and milder than in adults (16).
Molecularly, the link between the virus and ACE2 was explained, through a segment of viral protein S, comprising four residues (ARG449, PRO450, ARG453 and ASP454) nested in RBD. Residue ARG453 was connected coherently with LYS341 and GLU56 residues of ACE2 (11). Many hypotheses assumed that infection with SARS-CoV-2 makes a decrease in ACE2, internalized to ensure penetration into the cell (17). An immunohistochemical study has shown the strong presence of ACE2 on the alveolar parenchyma and smooth muscles of the lungs (18). One of the dangerous consequences of disease was breathing disorder, hypoxia was the most marked consequences of this epidemic, which can lead to mortality with dyspnea. A Western blot analysis for the quantitative measurement of the expression of ACE2 in the lungs of rats has shown that the content of the immunoreactive band decreases significantly with decreasing age. There had not a significant difference between adults and the elderly. This study agree with the results of this review and suggests that age influences the expression of ACE2(19).
This review effectuated can show the low prevalence of the disease in children. Results proved the low level of ACE2 in children (age < 18) and the link between the virus and ACE2 for cell penetration. The hypothesis was that the lack of ACE2 was a protective factor for children. Other data can support results of this review by reporting the age of illness persons by Sars-Cov-1. The outbreak due to Sars-Cov-1 during 2003 has shown that the highest attack rate in China was aged between 20 and 39 and they represent 53%, and in Canada the average affected age is 45 years. These reports were useful because there is a 75% close resemblance in amino acid sequence with Sars-cov-2, and ACE2 represented an entry point to the cell (20).
To show the hypothesis that the low of ACE2 was a protective factor. Not many studies have shown that, but there was a decrease in mortality and severity of diagnosis for patients on ACE inhibitors. ACE inhibitors can be used for blood pressure disorder or for heart disease. It causes a decrease in ACE2 levels for patients because it blocks the cascade of reactions leading to the synthesis of ACE2 (21). In addition, suppose that chloroquine and hydroxychloroquine have clinical efficacy in combating Sars-Cov-2. We checked its mechanism of action in previous studies to find a link to this review (22). These two treatments leaded to eliminate the glycosylation of ACE2 which is necessary for binding with the viral protein S (23). Theoretically, chloroquine and hydroxychloroquine played a role in the improvement of some cases and it reinforces that the level of ACE2 was essential for the attack of the virus and the degree of pathogenicity (22). Many therapeutic trials were effectuated to find the treatment of the disease. Experimental studies have shown that many oils had an impact on human health. Eucalyptus oil was one of this oils that made a significative amelioration of the illness persons suffering from coronavirus as the Sars-Cov-1. Studies showed the effect of Eucalyptus on ACE2 receptors. Eucalyptus has decreased the expression level of ACE2 and played the same role of ACE inhibitor. In addition, Eucalyptus is a bronchodilator when it will be inhaled and leads to decrease lung secretions. Researchers have not shown that Eucalyptus was a treatment, but there have shown the positive effect leading to ameliorate prognostic of patients suffering from Sars-Cov-2. We can suppose that Eucalyptus can be an adjuvant treatment(24) .
The literature suggest that diabetes was a risk factor for COVID-19, a meta-analysis has shown that 14.5% of patients with severe diagnostics are diabetic. Also, there have not a significative difference between the type 1 and type 2 of diabetes. It is true that diabetes affects the immune system and the individual will be more susceptible to infectious diseases in general (25). For example, Carey et al. have Showed that the ratio of the incidence rates of persons in hospital with infectious disease was 3.71 (95% CI 3.27–4.21) for people with T1D and 1.88 (95% CI 1.83–1.92) for people with T2DM (26). Not only that, but also, diabetes resulting the excessive expression of ACE2 in human tissues as well as in the lungs. This explained the binding of Sars-Cov-2 and ACE2 in the body and that the excessive expression of ACE2 is the factor that lead a high number of severe cases of diabetes in COVID unities. so diabetes is considered as a risk factor of Sars-Cov-2 (25).
This review of literature illustrated ideas that support our hypothesis and showed that the level of ACE2 played an important role in guiding the prognosis of patients infected with Sars-Cov-2. The high level of ACE2 has been shown to be a risk factor for worsening the situation, in contrast with children, whose expression of ACE2 was low compared to adults for physiological reasons was a protective factor (15).