In-depth analysis explains why preschoolers are less likely to develop severe COVID-19

Five years ago, at the start of the coronavirus pandemic, one phenomenon became very clear: Preschoolers rarely developed severe cases of COVID-19.

It’s not that children under 5 avoid infection. On the contrary, they caught COVID like everyone else. In the United States, the Centers for Disease Control and Prevention estimates that more than 90% of children, from infancy to age 17, have been exposed to SARS-CoV-2, the virus that causes COVID.

What differentiates the younger population of children is their generally striking avoidance of serious coronavirus infections. This fact has led scientists around the world to seek an answer to a deceptively simple question: how does the youngest population of children, wherever they are in the world, continually escape form serious from COVID?

Now, a large team of immunologists and physician-researchers from several institutions in France has conducted an in-depth study comparing the immune response of preschool children to that of older children and adults. The team focused on the adaptive immune response – the activities of T cells and B cells – to understand how the youngest among us are generally spared serious and even fatal infections.

“The main risk factor for severe (coronavirus) disease is age,” writes Dr Benoît Manfroi, lead author of the research, published in Scientific translational medicine. “Children are at the lowest risk and the elderly are the most vulnerable,” Manfroi added.

With other viral infections, the most susceptible populations are generally at two age extremes: the very young and the very old. The research team singled out influenza and respiratory syncytial virus (RSV) as two of several viruses responsible for significant morbidity and mortality in the two vulnerable age groups.

This rule of thumb, however, does not apply when the infection is caused by SARS-CoV-2 or any other coronavirus capable of causing serious infections. In the United States, the CDC characterizes preschoolers’ relationship with SARS-CoV-2 in another way: with statistics. Children under the age of 5 make up 6% of the total U.S. population, but only 0.1% of COVID-19 deaths have occurred in this age group. Preschoolers who developed severe COVID tend to have comorbidities, studies have shown.

To better understand the immune response to SARS-CoV-2 in preschool children, the French team conducted a large study including people of all ages, 89 participants in total. Included are preschoolers, older children and adults with mild or severe COVID before, during and 11 months after infection. Scientists have collected data on adaptive immune responses, also called acquired immunity, or pathogen-specific immune responses.

During SARS-CoV-2 infection, children younger than 5 years had lower, phenotypically distinct antiviral CD4 counts⁺ T cell response compared to older children and adults with mild disease. This younger cohort also developed phenotypically distinct memory T and B cell responses after recovery compared to participants in other age groups.

For example, unique memory T cells from preschoolers showed marked inflammatory features compared to other cohorts. And their virus-reactive memory B cells were fewer than those of older children and adults.

According to the French analysis, differences in the immune responses of older children and adults reflect the maturation of the immune system. Manfroi and colleagues suggest that the beneficial immune response unique to preschoolers allows them to consistently avoid serious infection.

“The immune system of preschool children is subject to unique external influences, being more frequently exposed to microbes than that of adults, particularly respiratory viruses, including endemic human coronaviruses,” Manfroi added, referring to four known coronaviruses responsible for the common cold. .

The emergence of SARS-CoV-2 was not the first time medical scientists observed extremely young patients avoiding serious illness caused by coronavirus. Children under the age of 5 have generally been spared serious infection when exposed to SARS-CoV-1, the coronavirus that sparked an outbreak in 2002-2003. Infections began in China before spreading elsewhere in Asia. SARS-CoV-1 has also spread to North America and South Africa.

The World Health Organization estimates that the mortality rate among young adults is between 10 and 15 percent, but among people 65 and older, mortality exceeds 50 percent. The usually mild illness in children younger than 5 has surprised medical scientists.

“Host resistance to infectious diseases is largely determined by the immune system, which takes several years to mature after birth. Infants initially rely on maternal antibodies and innate immunity, because the innate immune system matures more quickly than its adaptive counterpart,” said Manfroi, who was among dozens of scientists conducting a research component at INSERM, or the National Institute of Health and Medical Research in Paris.

Other collaborators came from the Institut Necker Enfants Malades; Pasteur Institute; Paris University Hospitals; Sorbonne University and Université Paris Cité, among other research centers. Outside of France, the team members were from Germany and Guyana.

The French results come on the heels of a study conducted by the United States and published in the journal Cell in 2023. Scientists at Stanford University in California led an international team that also concluded that preschoolers had milder cases of COVID-19.

The Stanford research found that among adults infected with SARS-CoV-2, virus-specific antibodies rose rapidly and then fell dramatically, decreasing 10-fold over six months.

Infants’ antibodies to SARS-CoV-2 increased more slowly and never declined. Antibodies remained at the same level or continued to increase throughout a 300-day observation period.

Lead researcher Dr. Bali Pulendran attributed mild bouts of COVID in preschoolers to an abundance of inflammation-promoting proteins — cytokines — in the nasal cavity. Key among these proteins was interferon alpha, which is notable for stopping viral replication in infected cells, Pulendran said in a statement.

Manfroi and his colleagues, for their part, acknowledge that their study had several limitations. “A first major limitation lies in the lack of assessment of tissues other than blood, particularly mucosal sites using either nasal swabs or adenoid or tonsil biopsies,” concluded the team, noting that “there have been reports that swab samples were taken from infants and young people.” children have significantly upregulated expression of inflammatory cytokines at mucosal sites during the acute phase of infection compared to adults.

© 2024 Science X Network