The novel coronavirus Delta variant was the pathogen of COVID-19 that broke out in Putian, Fujian province in September 2021. Compared with the early epidemic strain, the Delta variant had a higher replication and transmission ability [6]. In this study, there was no significant difference in SARS-CoV-2 viral load between children and adults infected with the novel coronavirus Delta variant. Angiotensin converting enzyme II is a target cell surface receptor for SARS-CoV-2 binding. Although the distribution of ACE2 and immune system characteristics in children are different from those in adults, they still have the same susceptibility to the novel coronavirus Delta variant.
The proportion of mild infections in children (50%) was higher than in adults (17.9%), and so were the proportions of cough and diarrhea symptoms. Children’s clinical symptoms and classification were mild, the possible reasons being as follows: [1] ACE2 is highly expressed in children’s lung tissue, and its expression decreases with age [7], which may cause children’s illness to be mild. [2] The pathogenesis and progress of COVID-19 are not only related to the direct damage of SARS-CoV-2, but also the immune damage caused by the excessive response of the immune system. Children’s immune systems are not yet mature, and it is possible that the activation of immune cells and the release of cytokines are reduced, so the tissue damage is not as serious as that of adults. [3] From the statistical results, it can be seen that there were more comorbidities in adults, than in children, which may also affect the severity of COVID-19.
After SARS-CoV-2 invades the human body, lymphocytes can be consumed and destroyed, resulting in a decrease in peripheral blood lymphocytes. It has been reported that 82.1% of COVID-19 patients have decreased lymphocytes, and 95.5% of them are patients with severe illness [8]. Multivariate logistic regression analysis showed that the lymphocyte count was one of the independent predictors of severe COVID-19. The counts of T cells, CD4+ T cells and B cells in patients with severe illness were significantly lower than those in patients with mild illness [9].This study found that the lymphocyte count of children was higher than adults, which is consistent with the clinical classification of children patients. In addition, the physiological increase of lymphocytes in childhood is also one of the reasons for the lymphocyte count in children being higher than in adults.
The cytokine storm induced by the excessive immune response of the host is one of the main pathogenesis mechanisms of COVID-19 [10]. Interleukin-6 (IL-6) is a cytokine of the chemokine family, produced by pulmonary interstitial cells and almost all immune system cells. Overexpression of IL-6 plays a key role in the activation and development of the cytokine storm [11]. Studies have shown that the level of IL-6 in patients with severe COVID-19 was significantly higher than in patients with mild COVID-19 [12, 13]. A meta-analysis involving nine COVID-19 studies showed that the increase of IL-6 was positively correlated with the severity of COVID-19 [14]. The results showed that the level and elevation rate of IL-6 in children were lower than in adults suggesting that the inflammation in the children was mild.
In our previous meta-analysis, we found that there were great differences in liver function indices between patients who died owing to COVID-19 and those who survived [15]. This study found that liver injury occurred in both children and adults. The ACE2, binding receptor of SARS-CoV-2, is highly expressed in bile duct epithelial cells. Thus, SARS-CoV-2 can directly infect bile duct epithelial cells and further cause liver injury. After the body infection with SARS-CoV-2, the release of numerous proinflammatory cytokines and free radicals caused by excessive immune response, can also cause nonspecific inflammation of the liver, and increase ALT, AST and even bilirubin [16]. Possible reasons for the lower frequency of liver injury in children include:
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(1)
The children’s immune systems are not perfect, so the nonspecific inflammation of liver is mild.
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(2)
Some adults use all-human monoclonal neutralizing antibodies, thymosin, and other drugs, to treat their comorbidities, whereas children do not use these drugs. Therefore, drug-induced liver injury in adults, considering these factors, cannot be completely ruled out.
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(3)
According to the national epidemiological survey, the prevalence rates of HBsAg among people aged 1–4, 5–14, and 15–29 years are 0.32%, 0.94% and 4.38%, respectively [17]. Therefore, children may have a lower HBsAg positive rate than adults, which may also cause the difference of abnormal liver function between the two groups.
SARS-CoV-2 binding receptors are not only distributed in the respiratory tract and bile duct epithelium, but are also highly expressed in the kidney, mainly distributed in proximal tubules, afferent arterioles, collecting ducts and thick ascending branches of the Helen duct [18]. SARS-CoV-2 can infect the kidneys by binding with ACE2 or other receptors, which directly leads to kidney injury [19]. After virus infection in the kidney, ACE2 expression can be down-regulated [20], which inhibits the degradation of angiotensin II, which further leads to renal fibrosis [21].
In addition, immune disorders and cytokine storms induced by SARS-CoV-2 can also lead to kidney injury [22]. This study found that proteinuria could occur in both children and adults. The proportion of positive urinary protein is much higher than that of elevated serum creatinine. It is suggested that children with COVID-19 are as prone to kidney injury as adults, and renal tubules are the main site of renal injury. The urinary protein in the children was mainly a little ~ 1+, and proteinuria disappeared quickly with the improvement of the disease, suggesting that kidney injury was mild and recovered easily. The level of serum creatinine in adults was higher. Should be noted, the adults tend to have higher serum creatinine levels than those in children in physiological condition. Therefore, it should be cautious that whether the higher serum creatinine level in the adults group can be attributed to COVID-19. In addition, exogenous creatinine intake, and age also influence serum creatinine levels.
To sum up, differences exist among children and adults infected with the Delta variant COVID-19 in clinical manifestations, clinical classification, inflammatory indices, and biochemical indices. The children’s conditions were relatively mild. In conclusion, compared with the adults with delta variant COVID-19, children tend to have lighter clinical manifestations, higher lymphocyte count, lower IL-6 level, less frequent liver injury, and milder clinical typing. Practitioner should pay attention to the differences in the clinical manifestations between the adults and children. Understanding these differences is helpful to develop tailored treatment plans. The highlights of this study are as follows: (1) the number of children with Delta variant COVID-19 was large, 80 cases; and (2) the clinical symptoms, blood routine, IL-6, liver function, kidney function, urine protein, and viral load of children and adults with the Delta variant of COVID-19 were comprehensively compared. Few articles have compared the clinical characteristics of the two groups in such detail.
Limitations include the following (1) this paper is a retrospective study rather than an analysis and (2) the viral load of SARS-CoV-2 is indicated by a cycle threshold, which is not accurate enough.