Coronavirus in children and the theory of the Thymus Gland

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There is recent concern that a third wave of COVID-19 is likely to affect children more than adults. However, it appears science has a different agenda on this with regards to children and how they fight COVID-19.

For instance, in a recent statement released by the Indian Academy of Pediatrics (IAP), a representative association of Pediatricians on May 22 stated that “Children are as susceptible as adults and older individuals to develop infections, but not severe disease. It is highly unlikely that the third wave will predominantly or exclusively affect children” the report said.

The association also agrees that pandemics tend to occur in waves and each wave causes a large number of cases. Eventually, most of the population may get immune by asymptomatic or symptomatic infections (herd immunity). Over time, the disease may die out or become endemic in the community with low transmission rates.  The association released a detailed information to clarify their position on why children will not be affected in any event of third waves.

They explained that in the first wave, the severe disease occurred primarily in the elderly people and individuals with co-morbidities. In the current (second) wave, large number of younger age group (30-45 years) individuals have developed severe disease as well as those without co-morbidities. Hence, it is believable that there is a possibility of a third wave which is likely to infect the remaining non-immune individuals; and that may include children as well. The case of the disease in children is the subject for discussion in this article.

Studies on COVID 19 and children

Rehman et al., (2020) confirmed that the current trend suggests children may get infected but will be less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012 respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute a maximum number of the confirmed cases (308,592) and deaths (13,069) as of 22nd March (https://www.worldometers.info/coronavirus).

In India

In a recent serosurvey conducted by the All India Institute of Medical Sciences (AIIMS), New Delhi, it was discovered that it is highly unlikely for any future wave of Covid-19 by the prevailing variants of coronavirus to disproportionately affect children aged two years or older. AIIMS collected data between March 15 and June 10, 2021 from 4,509 participants across four states in India, of which 700 were less than 18 years of age and 3,809 were above 18. The interim study found seroprevalence (the prevalence of Covid antibodies) in 55.7 per cent of those between 2 and 17 years of age, and in 63.5 per cent of those above 18. “There was no statistically significant difference in prevalence between adults and children,” the study said.

A large proportion of children had asymptomatic Covid-19 infection. The overall seroprevalence was found to be 65.9 per cent.

The second nationwide seroprevalence study done in August-September 2020 found 9 per cent of the 3,021 children aged 10-17 years seropositive. The latest study by AIIMS has found 60.3 per cent of those in the age range of 10-17 years were previously infected with Covid. AIIMS scientists noted that since schools were closed during the pandemic, children were likely to have caught the infection from household adults. It is not clear, however, if children produce the same level of antibodies as adults when infected, the study said.

The AIIMS study is part of an ongoing large multi-centric population-based seroepidemiological study being conducted in five selected states with a proposed sample size of 10,000 individuals.

In Delhi, the survey found that irrespective of age groups, rural sites had lower seropositivity compared to urban areas. Within rural areas, children had slightly lower seropositivity compared to adults.

Seroprevalence in children was slightly more among female participants (59 per cent) compared to males (53 per cent). Children aged 2-4 years and 5-9 years had almost identical seropositivity rates of 42.4 per cent and 43.8 per cent respectively. This was lower than the rate observed for children aged 10-17 years at 60.3 per cent. “The higher seropositivity rate in children aged 10-17 years may be reflective of their higher mobility and independence compared to the younger children,” the study said.

The study also found that the seropositivity rate was higher at 74.7 per cent compared to the fifth serosurvey conducted in January 2021 in Delhi, where 56 per cent of the population surveyed showed signs of previous infection.

Four rural sites were included in the survey, of which Gorakhpur was the worst affected with seroprevalence of almost 88 per cent while Faridabad was the least affected with about 59 per cent showing signs of past Covid infection. The data was collected from Delhi urban resettlement colony, villages in Faridabad district under Delhi NCR, rural parts of Bhubaneswar, Gorakhpur, and Agartala.

The case of China and children

Also, in China for instance, one article published in Nikkei Asia, (2020) also confirmed that in Wuhan Children’s Hospital, the only mandated hospital for children confirmed with or suspected of COVID-19 infection. As of March 8, 2020, the hospital had treated 683 children including confirmed and suspected cases. Of these, 419 have been discharged. Most infected children and infants have mild symptoms, and severe cases account for only about 5% of confirmed cases according to report.

Another study published on March 14 by Nature Medicine examined 10 children with COVID-19 at Guangzhou Women and Children’s Medical Center. Researchers established that none had symptoms common in adult patients, such as difficulty in breathing, muscle pain, headache and nausea. The study further demonstrates that seven children had fever, but no higher than 38.9 C, and one had no symptoms.

All 10 children were tested for the virus because they had close contact with diagnosed patients. Chest X-rays of the children were either normal or showed only coarse lung markings without unilateral or bilateral pneumonia. Only few cases had leukopenia, leukocytosis, lymphopenia or elevated transaminase, which are frequently seen in adult patients, the study found.

Another preprint paper published by The Lancet medical journal of 50 children reported analogous findings. 46 of the children had mild or very minor symptoms and two had no symptoms at all, according to the authors, a team at Wuhan Children’s Hospital and Wuhan Tongji Hospital. The study disclosed that percentages of symptoms such as fever, cough and fatigue were reduced than in adults, however, more children had diarrhea than adults. The studies have linked the less severe nature of the disease in children to a fully functional thymus in children.

Thymus: The children’s Messiah?

The thymus is a largely neglected organ but plays a significant role in the regulation of adaptive immune responses. On why children are not being affected severally as compared to adults, the Indian Academy of Pediatrics (IAP) explained that children have been relatively less affected so far due to several factors. The most important reason is the less expression of specific receptors to which this virus binds to enter the host and also their immune system. A very small percentage of infected children may develop moderate-severe disease. If there is a massive increase in the overall numbers of infected individuals, a larger number of children with moderate-severe disease may be seen. Almost 90 per cent of infections in children are mild/asymptomatic. Therefore, the incidence of severe disease is not high in children.

The thymus is key in helping children to fight the pandemic, according to studies. Thymus gland plays critical role as an immune and endocrine gland, and its activity changes with progress of age, so its hormones and immune cytokines change according to the age phase and against the antigen attacked. Shrinking of the thymus takes place with age. For Glazer and Ko, (2020), the thymus is unique in that it reaches maturity in utero and is at its largest and most active in children.

For instance, at puberty, it slowly becomes less active, and the glandular tissue begins to shrink. This continues throughout a person’s life. By the time one gets to their mid-60s, the thymus is mostly inactive. By mid-70s, the gland is replaced with fat. This reduction in thymus function is believed to be one of the reasons why in later years, older adults become more susceptible to disease and infection.

Emerging research into COVID-19 has shown a marked decrease in the number of T-cells in some gravely ill patients. Scientists are now asking whether age-related thymus decline, which means T-cells aren’t quickly replaced, may play a role in the severity of illness seen in older adults. The flip side of this is whether due to their robust production of T-cells, children’s immune systems are able to stay one step ahead of the novel coronavirus. It’s only a working theory, but it shows promise and research into how this may affect and inform treatment going forward.

For instance, Gunes et al.,(2021) is of the view that the adaptive immune response mediated by the thymus is a process that regulates the immune response responsible for preventing invasive damage from a virus. Regulatory T cells (T-reg) are active during the early periods of life and have precise roles in immunomodulation. The thymus is highly active in the intrauterine and neonatal period. Thymus and T cells are the key factors of pathogenesis of SARS-CoV-2 in children.

In conclusion, humans have three types of immunity; innate, adaptive, and passive:

Innate immunity: Everyone is born with innate (or natural) immunity, a type of general protection. For example, the skin acts as a barrier to block germs from entering the body. And the immune system recognizes when certain invaders are foreign and could be dangerous.

Adaptive immunity: Adaptive (or active) immunity develops throughout our lives. We develop adaptive immunity when we’re exposed to diseases or when we’re immunized against them with vaccines.

Passive immunity: Passive immunity is “borrowed” from another source and it lasts for a short time. For example, antibodies in a mother’s breast milk give a baby temporary immunity to diseases the mother has been exposed to.

 

Take home

Though children can get coronavirus, their cases are less severe than in adults. Interestingly, some studies showed that only about 5% of coronavirus infections in children are severe. So the question is; are children immune to the new coronavirus? From studies, the answer is no, however, most infected children experience relatively mild symptoms that differ from those observed in adults and the thymus gland in children is seen as the ‘magic’ player in fighting the disease severity in children.

About the Authors

Dr. Raphael Nyarkotey Obu, is an honorary Professor of Naturopathy, Naturopathic Consultant, level 300 law student and president, Nyarkotey College of Holistic Medicine, and Lawrencia Aggrey-Bluwey, is a Clinical Nurse, Health Services Manager and an Assistant Lecturer with the Department of Health Administration and Education, University of Education, Winneba. She is also a PhD student in Health Policy and Management, at the University of Ghana, Legon. Contact: [email protected].

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