An international meta-analysis looking at research on COVID-19 in young children has found that infants are more likely to catch the novel coronavirus than those aged between one and five, although symptoms throughout this demographic remain mostly mild.

The systematic review1, which was published in the journal Vaccine in December, also found that almost half of those infected under five years old were asymptomatic in findings which could help inform future policy decisions relating to vaccination programs for young children and expectant mothers.

Led by the University of New South Wales, the scientific collaboration examined almost 2,000 papers, whittling this down to 65 of the highest quality research on COVID-19 and young children. The review aimed at filling a key knowledge gap on the clinical characteristics of COVID-19 in those under five.

However, the researchers say that future studies are still needed, in particular to uncover the potential risk of transmission from infants to their parents and caregivers and to examine whether children who are asymptomatic can spread the disease.

Under fives most at risk of respiratory infections

Senior author Dr Nusrat Homaira of the Discipline of Paediatrics at UNSW Medicine and Sydney Children’s Hospital said that while there had been systematic reviews on the whole population, none had specifically looked at children under five years old.

“We chose to focus on the under-fives because they are the most at-risk age group for respiratory infections and respiratory infections are one of the most common reasons why children are hospitalised – so, it is important to have a clearer understanding of COVID-19 infection and its severity in children under five,” she said.

“Secondly, children often have asymptomatic infection generally and play a significant role in transmission of respiratory infections within the community – which is why immunisation is often targeted at that age group for infections like the flu – so, we wanted to understand all those issues in light of COVID-19.”

The 65 studies examined were conducted in 11 countries during the first wave of the pandemic, and represented over 1,200 children under five years of age infected with laboratory-confirmed COVID-19.

The review found that young children generally developed mild COVID-19 symptoms and caught the disease through community sources.

The data was current as of June 4, 2020. As of July 28 that year, there were over 16.6 million confirmed cases of COVID-19 globally with more than 656,000 deaths.

Immature immune systems put infants at risk

The meta-analysis found that 50 per cent of the cases were in infants (children aged less than one year) and 53 per cent of cases were male. The pooled results showed that 43 per cent of cases were asymptomatic.

Only seven per cent of cases in young children had severe symptoms that required admission to the intensive care unit (ICU), compared to 53 per cent in adults.

These results showed that infants more frequently became infected with COVID-19, Dr Homaira told Lab Down Under.

“Generally respiratory infections including influenza, RSV and rhinovirus disproportionately infect infants due to their immature immune system. Our study confirms that COVID-19 may also disproportionately infect infants more compared to children aged one to five years of age.”

Because half of infected children were under one year old, Dr Homaira said this could affect vaccine roll out programs in future.

“Our study showed that 50 per cent of children were infants which may have implications in terms of maternal vaccination (during pregnancy) to protect infants against COVID-19 infection as infants, specifically those aged less than six months, are often not suitable for vaccination.”

Another area of concern unveiled by the study was that 71 per cent of young children were treated by antibiotics despite COVID-19 being a viral disease.

“COVID-19 is an emerging disease so globally physicians are trying out different treatment modalities. However COVID-19 is a viral infection and excessive inappropriate use of antibiotic without evidence of concurrent bacterial infection may contribute to emergence of antimicrobial resistance which remains a major public health threat. Antibiotics are commonly inappropriately used to treat viral respiratory infections in children.”

The meta-analysis highlighted a need for ongoing monitoring of antibiotic use for COVID-19 infection in children, Dr Homaira told Lab Down Under.

Transmission between mum and bub

The review also examined the potential for “vertical transmission” of COVID-19 from pregnant women to their newborn babies. Out of 139 newborns who had laboratory confirmed COVID-19 infections, five of these were infected within several hours to a few days of being born.

“However, whether the newborns acquired it from their mothers or not was unclear because none of those studies could persuasively claim mother to neonate transmission,” Dr Homaira said.

“So, more research is needed to understand if children born to women who have COVID-19 during pregnancy have an increased risk of acquiring the infection and what the long-term outcomes are for newborns with the disease.”

Any potential risks of vertical transmission had possible ramifications for the rollout of vaccinations as well. While vaccines were an important public health intervention, Dr Homaira said that newborns’ immune systems were not suitable for many vaccines.

However, maternal immunisation was already being used for vaccine-preventable diseases such as whooping cough, tetanus and influenza to provide added protection during the first few months of life, she said.

“When we wrote our paper in July, there was no COVID-19 vaccine available but now several countries have started administering multiple COVID-19 vaccines which are being offered to healthcare workers, people over 80 years old, and residents and staff of nursing homes in the first phase.

“As the vaccine is being rolled out to the whole population and other parts of the world, maternal immunisation could be a viable preventive approach – particularly given we found half of COVID-19 infections in the under-fives were among infants.”

Further research on COVID-19 and children required

Dr Homaira said the meta-analysis was likely the most comprehensive systematic review of scientific literature on children under five years of age with laboratory-confirmed COVID-19 infections conducted thus far.

While 90 per cent of children included in the review developed mild to moderate COVID-19 symptoms, there was a need for further research on the subject, researchers say.

“Our meta-analysis shows almost half of young COVID-19 cases were asymptomatic and half were infants, illustrating the need for ongoing monitoring to better understand the epidemiology, clinical pattern and transmission of COVID-19 in order to develop effective preventive strategies against the disease in young children,” said Dr Homaira.

“So, while it’s unlikely for COVID-19 to be a severe disease for the under-fives, it’s still important for children to be tested if they develop respiratory symptoms and then standard precautions should be followed if they are positive.”

The review was led by UNSW Sydney and included researchers from Telethon Kids Institute Perth, The University of Sydney, International Centre for Diarrhoeal Disease Research Bangladesh and The Royal Veterinary College University of London.

Author’s note: If you enjoyed this article, you can follow Lab Down Under on Facebook and LinkedIn or support me on Patreon. I also have my own personal Twitter account where I’ll be sharing my latest stories and any other items of interest. Finally, you can subscribe here to get my blogs in your inbox.

1 Bhuiyan MU, Stiboy E, Hassan Z, Chan M, Islam S, Haider N, Jaffe A, Homaira N. Epidemiology of COVID-19 infection in young children under five years: A systematic review and meta-analysis. Vaccine, 5 December 2020.

Featured image: Asian child COVID-19. Picture by Leo Fontes. Used under the Pixabay Licence.

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