The impact of COVID-19 on children has reached a time of concern.
According to data from the US CDC in March 2022, the proportion of children among all COVID-19 patients is about 18%, and more than 118,000 children are hospitalized for COVID-19. Of these, nearly 1,400 died, and 321 patients aged 5 to 11 years. In the fifth wave of the Omicron epidemic in the United States, the number of cases and hospitalizations among children reached the highest number since the epidemic.
Epidemiological studies in some European countries have yielded the same results as above. In the two years since the COVID-19 pandemic, comparing child and population-wide data, hospitalization rates and fatality rates in children's groups have increased slowly compared with the original strain, and the future trend of this upward trend seems to be continuing.
Contrary to the overall decline in the hospitalization rate and mortality rate of the new crown, the pathogenicity of the new crown virus in the child population is increasing, which should be more alarming.
Vaccines should be the first option in children's prevention and control measures, and recombinant protein vaccines should be the best option for benefit/risk ratios than mRNA vaccines with higher adverse reaction reporting rates in children.
Rising pathogenicity of COVID-19 in children?
Between January 7 and 15, 2020, Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology conducted a retrospective study of 366 children under 16 years old, from which 6 children tested positive for the new crown virus were found, one of whom needed to be admitted to the intensive care unit for treatment. They are between the ages of 1 and 7.
Evidence at the time showed that children and young people were less susceptible to COVID-19.
On March 19, 2020, the New England Journal of Medicine quoted a study by the Chinese CDC that less than 1% of cases were children under the age of 10. A total of 171 (12.3%) of the 1391 children assessed and tested were diagnosed with COVID-19. The median age of the confirmed child was 6.7 years.
Most infected children have milder clinical symptoms compared to infected adults, and asymptomatic infection is more common.
But since the Delta epidemic strain began, the pathogenicity of the virus in children began to rise.
In April 2021, the Delta epidemic strain began to become popular worldwide.
In August 2021, the US CDC reported that about 400 children under the age of 18 died from COVID-19. According to the American Academy of Pediatrics (AAP), in the week of October 28, new infections among people aged 5 to 11 accounted for 1/4 of the total number of new infections in the United States. By mid-October, at least 23,000 children aged 5 to 11 years in the United States had been hospitalized, and about one-third required intensive care. Among infected people under the age of 18, the CDC has recorded a total of 745 deaths.
Since the beginning of the COVID-19 pandemic, children have accounted for nearly 15 percent of all cases in the United States.
But the proportion of infected children is much higher during the Delta epidemic: In the week ending 26 August 2021, children accounted for about 22.4 percent of COVID-19 cases in the United States.
With the advent of the new Omicron variant, the case fatality rate of real-world COVID-19 infections continues to decrease significantly due to vaccination (the most critical factor), the use of new drugs, and the reduced virulence of the COVID-19 variant. Especially in people aged 18-50 years, the infection rate has increased significantly, but the hospitalization rate and case fatality rate have decreased significantly.
But the situation is different in children.
On March 17, 2022, the number of daily confirmed cases in South Korea exceeded 620,000, the highest number in South Korea. According to the South Korean Department of Disease Control and Prevention on April 9, 1887337 children aged 9 and under in South Korea have been infected with the new crown virus. This means that on average, nearly 50,190 out of every 100,000 children in this age group are infected with the new crown virus, and half of all children are infected cumulatively, which is the highest proportion among all age groups.
According to the US CDC in March 2022, the proportion of children among all COVID-19 patients is about 18% (as of August 19, 2021, the proportion was 14.6%). More than 118,000 children were hospitalized for COVID-19, of which nearly 1,400 died, of which 321 were between the ages of 5 and 11. In the fifth wave of the Omicron epidemic in the United States, the number of cases and hospitalizations among children reached the highest number since the epidemic.
The above is a graph of the cumulative number of child deaths from three official channels in the United States, and in the first quarter of 2022, the hospitalization rate and mortality rate of children are the highest since the pandemic.
As the chart above shows, the number of COVID-19 deaths since 2020 in the 0-17 age group in the United States has exceeded the number of people who have died of influenza in the 17 years from 2004 to 2021 combined.
Epidemiological studies in some European countries have yielded the same results as above. In short, since the 2 years of the new crown global pandemic, comparing the data of children and the whole population, the hospitalization rate and fatality rate in the child group have risen slowly compared with the original strain period, and the future trend of this upward trend seems to be continuing, which is very noteworthy.
The critical illness rate in children is still much lower than in adults
Some underlying conditions increase the likelihood of severe COVID-19, such as obesity and diabetes, but children rarely have such conditions. At the same time, the nasal passages of children contain fewer ACE2 receptors that coronaviruses use to enter cells, and airway cells show differences that contribute to early detection of the virus to some extent.
Children's immune systems are not yet well developed, which can be an advantage.
It is generally believed that severe COVID-19 cases and deaths are often caused not by the coronavirus itself, but by the "cytokine storm" of the immune system's overreaction to attack lung inflammation, which is very rare in children.
Rapidly recruiting cellular immune responses in the early stages of infection can reduce the severity of pneumonia. During the acute phase (within 14 days after infection) and the convalescent period (15–57 days after infection), children had fewer monocytes and fewer inflammatory monocytes compared with adults; children had lower responses to memory CD4+ T cells and memory CD8+ T cells, and usually had a significant increase in T cell response with age, and children responded less to new coronavirus T cells and had fewer memory T cells during the memory phase effect. Adults and children have comparable ability to respond to the new coronavirus recruitment T cells, but the baseline levels of immunity are different. This means that lower baseline levels of immunity in children may be mildly associated with post-infection symptoms.
Children's T cells are more "primitive" than adults, and they are specifically designed to identify specific pathogens. By the time a person reaches their 30s, many of these protocells will encounter pathogens and transform into "memory" T cells, and they can respond more quickly if they encounter the same or similar pathogens again.
At the same time, the body's rate of producing raw T cells slows down. So when entirely new pathogens like COVID-19 emerge, adults don't have as many proto-T cells to recognize and respond to new threats. In some ways, they are more adapted to encountering a new pathogen. It is also possible that the new crown virus has been largely eliminated by the child's body before the emergence of those specialized T cells. This clearance is done by the innate immunity of the immune system, which also differs between young and old: cells such as macrophages and neutrophils that devour foreign invaders and debris, and this rapidly responding cellular system in adults tends to be inefficient. Studies have found that children and adolescents under the age of 24 have higher levels of IL-17a and IFN-γ cytokine proteins in their blood, which direct an innate immune system to attack. This histone factor also recovers much faster than adults.
The study also found that children with COVID-19 produced fewer types of targeted antibodies and fewer than adults. This could be because they don't need it, or because the innate immune system has already processed the infection.
Compared to adults, children have fewer total monocytes and fewer inflammatory monocytes. The latest research has found that the new crown virus infects immune cells, causing inflammatory necrosis of monocytes and lung macrophages. In the blood of patients with new crown, about 6% of monocytes are experiencing pyroptosis, also known as inflammatory necrosis, and the scorched cells continue to expand until the cell membrane ruptures, releasing cytokines and chemokines.
In the early stage of infection, these scorched cells release substances as an "alarm", which can recruit other immune cells to the site of infection and remove pathogens in time, but when more and more scorched cells are killed, a large number of inflammatory molecules are released, and the inflammatory response is out of control, resulting in respiratory distress and systemic multi-organ failure. The more scorched cells, the more severe the symptoms of the patient, and the level of coke death markers in the blood of severe patients increased significantly compared with patients with mild and moderate symptoms of covid-19.
However, because children have fewer monocytes and fewer inflammatory monocytes, scorch death is less likely to occur. This also partly explains that children have milder symptoms, are less prone to respiratory distress and systemic multi-organ failure, and that the critical illness rate of COVID-19 in children is much lower than that of adults.
Vaccination reduces the risk of infection in children
From the latest global epidemiological data analysis, it can be found that the hospitalization rate and case fatality rate of children have increased. In the future, with the continued epidemic of the new crown, the opposite direction of the decline in the hospitalization rate and mortality rate of the new crown is the upward trend of children's pathogenicity, which should be more alarming.
Vaccines should be the first option in children's prevention and control measures, and recombinant protein vaccines should be the best option for the benefit/risk ratio than mRNA vaccines with higher adverse reaction reporting rates in children.
In August and October 2021, the United Arab Emirates and Bahrain announced, respectively, that they would start an inactivated COVID-19 vaccine produced by Sinopharm in children. The age of vaccination approved by the two countries is 3 to 17 years old and 3 to 11 years old, respectively;
On November 2, 2021, the US CDC officially approved the expansion of the recommended range of the new crown vaccine to the age group of 5 to 11 years old, and the recommended scope of the new crown vaccine to the age group of 5 to 11 years old, and allowed to be vaccinated as soon as possible;
Cuba has the lowest initial vaccination age in the world. From September 3, 2021, people aged 2 to 18 in the country began to receive Cuba's self-developed COVID-19 vaccines "Sovereign 02" and "Sovereign Plus".
Since mid-October 2021, many places in China have started vaccinations for people aged 3-11 years, requiring 2 doses with 3 weeks of intervals between each dose. The vaccines used are in the same dosage and dosage form as those aged 12 years and older.
According to data from the CDC in February, about 66 percent of the U.S. population has been fully vaccinated, including three-quarters of adults and nearly 90 percent of the elderly. Among adolescents aged 12 to 17 years, the national vaccination rate is also higher than 50%. But at present, less than 28% of children aged 5 to 11 in the United States are fully vaccinated.
The FDA statement said that a Phase 3 clinical study of 4638 children showed that in the endemic environment of the Delta strain, 5 to 11 years of age were 90.7% effective in preventing infection after receiving two doses of the Pfizer mRNA vaccine. 1 month after receiving the second dose of the vaccine, the average titer (GMT) of neutralizing antibodies in children was 1197.6. This is comparable to the immune response (GMT of 1146.5) in those vaccinated with 30 μg in the 16-25 age group.
A study in the New England Journal of Medicine found that vaccination is currently a key factor in preventing infection, reducing the risk of hospitalization in children aged 5 to 11 years by 68%.
The impact of influenza on children's health is decreasing. Perhaps because of the widespread wearing of masks and social distancing over the past two years, the impact trend has weakened since April 2020.
Here's a comparison of the two sets of data. From 2020 to 2021, only 9 children in the 5-11 age group in the United States were admitted to the hospital due to influenza, and at the same time, millions of children in the same age group were admitted to the hospital; since the new crown pandemic, 6 children in the 0-17 age group in the United States have died of influenza, and at the same time, more than 1200 children in the same age group have died of the new crown.
We know that the most effective means of preventing influenza is vaccination, and pre-stored antibodies after vaccine immunization are the best protective tools to protect children from the threat of death.
The new crown vaccine is not only accessible, but also in the northern hemisphere billions of people have also achieved a good effect on epidemic prevention and control, in the future prevention and control of the new crown epidemic strategy, second only to protect the elderly group is the child's new crown vaccination.
According to an earlier statement by the World Health Organization (WHO) (before 2021), children and adolescents who are infected with the new crown virus will have milder diseases than adults. Children in the non-high-risk group are not the first to be vaccinated compared to the elderly, chronically ill and healthcare workers. The WHO calls on governments to carefully review the order of their vaccination programmes.
At present, the mainland is intensively promoting COVID-19 vaccination for the elderly population; then, it is time to consider how to strengthen the vaccination of children. When children are vaccinated, what technical route products should be chosen for the booster needle? How to choose the dosage? What is the vaccination schedule? How to solve the accessibility of vaccines needs to be considered.
The author of this article is a virologist of the Chang RongShan family.
Written by | Chang rongshan
Li Lin | responsible editor
This article was first published on the WeChat public account "Eight Points Health" (ID: HealthInsight)
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