Why Babies Are More Resilient Against Covid-19
Understanding infants’ peculiar response to the virus may be a key to finding new treatments

By Mariana lenharo (Sep 28, 2020 in ELEMENTAL, your life, sourced by science-media.com)


Photo: Sirapat Saeyang/EyeEm/Getty Images

Babies make up a tiny percentage of all diagnosed cases of Covid-19. In the United States, where 1.2% of the population are children under one year of age, they account for only 0.27% of the positive tests, according to a Centers for Disease Control and Prevention (CDC) report. It’s not clear if babies are getting infected at a lower rate compared with other age groups or if they are just not being tested as much. But what is evident is that the ones who are diagnosed have, in general, significantly milder illness compared with adults.

The reason behind babies’ apparent resilience to Covid-19 is being intensely investigated by scientists. Getting to the bottom of that mystery could inspire the development of new treatments, potentially benefiting people of all ages.

What’s known so far about the outcomes of babies infected with SARS-CoV-2 comes from reports such as the one published in this month’s edition of The Journal of Pediatrics by physicians at the Ann & Robert H. Lurie Children’s Hospital of Chicago. The study, which included 18 previously healthy children under 90 days old who tested positive for Covid-19, showed that none had severe symptoms. Nasal congestion was seen in 28%, cough in 44%, and vomiting or diarrhea in 22%. The study sample is very small (again, the number of infants who test positive is a low figure overall), but the researchers say the early findings provide some potentially important insights.

“It’s notable that a large percentage of them had fever as maybe even the only symptom,” says lead author Leena B. Mithal, MD, a pediatric infectious diseases expert from Lurie Children’s and assistant professor at Northwestern University Feinberg School of Medicine. “None of the babies required any oxygen or any respiratory support at all,” she adds. “This is a small series, but what we saw during that period has remained true moving forward in the cases of previously healthy infants.”

Scientists have a few theories that could help explain why the novel coronavirus is mostly harmless to healthy babies. One of them has to do with the receptor that SARS-CoV-2 uses to enter human cells. The expression of this receptor, called ACE2, varies with age and is less present in babies and children compared with adults. The hypothesis is that, in the youngest people, the virus finds fewer keyholes it can unlock to get inside the cells and replicate.

“An additional hypothesis proposed for the mild infection in young children is their strong ability to mount primary immune responses mediated by T-cells,” says pediatrician Petter Brodin, MD, PhD, a researcher at the department of women’s and children’s health at Karolinska Institute in Sweden. T-cells, along with antibodies, are part of our adaptive immune system, whose function is to target pathogens like SARS-CoV-2. The fact that babies have a large repertoire of naive T-cells, which are able to recognize new invaders and develop into mature killer cells, is probably important to explain their effective response to the virus, Brodin says.

Brodin also notes that, at least until puberty, children’s immune systems are calibrated differently from those of adults, and this could protect them from the sequence of events that usually leads to severe disease, including a poor initial response by interferons (proteins that act as “first responders” against viruses), a poor response of the adaptive immune system with T-cell exhaustion, and hyperinflammation driven by massive tissue damage.

Another theory is that young children, including infants, might have more recent exposure to common cold coronaviruses, which could potentially modulate their immune response to SAR-CoV-2 infection. “Although adults have likely been exposed to those coronaviruses as well, it’s common to get many colds in the first decade of life and there may be some cross-protection,” says Mithal. It’s not clear, though, if babies are currently as exposed to these other coronaviruses as they normally would, given the social isolation measures in place.

Although these theories are yet to be proven, at this stage of the pandemic there is enough epidemiological data to confidently state that infants are in general protected from severe illness. So much so that the American Academy of Pediatrics has updated its recommendations regarding newborns and mothers with symptomatic Covid-19 at the time of delivery. AAP now does not recommend universally separating babies from Covid-19-positive mothers, as long as they are well enough to take care of the baby and take the necessary precautions to decrease transmission.

“Over time, it seems that babies who went home with moms infected with SARS-CoV-2 at the time of delivery did not do significantly differently or have worse outcomes than babies who were separated from their mothers in the initial postpartum period,” says Mithal. “This speaks to the fact that, of these babies at risk of exposure and infection in the household, only a small subset may have symptomatic infection and further problems.”

Observing how children and infants respond to the virus may lead to new therapies for Covid-19.

This doesn’t mean that babies cannot get severe symptoms. Alvaro Coronado Munoz, MD, a doctor specialized in pediatric critical care and an assistant professor at McGovern Medical School at UTHealth in Houston, learned that lesson when he and his colleagues treated a three-week-old boy who was admitted to the pediatric intensive care unit in with low blood pressure, tachycardia, rapid breathing, and hypothermia. He had presented nasal congestion for two days and had an X-ray consistent with Covid-19 infection. A nasal swab confirmed the diagnosis.

“It was one of the first cases reported in the U.S. of critical care admission of a pediatric patient with Covid-19. It was very early in the pandemic and there was all this information regarding the fact that pediatric patients were less affected, so it was a little bit of a surprise,” says Munoz. The boy had to receive mechanical ventilation for five days and survived after intensive care. “This case was very important to recognize that an infant can become as sick as adult patients. So, don’t just assume that it’s something else.”

Observing how children and infants respond to the virus may lead to new therapies for Covid-19. One of the treatment strategies that is being explored is how to combat a harmful type of inflammation sometimes seen in the acute phase of the infection. “We hope to learn from ongoing studies that certain inflammatory pathways are differentially activated in children with mild infection compared to adults with severe disease. Maybe then we can develop more targeted immunomodulating therapy that we can apply to those with more severe illness, including adults,” says Mithal.

Another avenue of research is looking at the strong initial interferon response, which is probably critical for early antiviral defense and is a system that the SARS-CoV-2 directly interferes with, according to Brodin. This is most likely a mechanism that protects babies and children and it is possible that triggering the same response in adults could help protect them as well.

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Although children in general are at a lower risk of Covid-19 complications, one issue that has been setting babies apart from older children is the incidence of the multisystem inflammatory syndrome in children (MIS-C), a recently identified condition associated with the novel coronavirus. Although rare, this is a serious and potentially fatal condition that appears after the Covid-19 infection in which different parts of the body become inflamed. So far, it has been identified mainly in older children, with a large percentage of cases concentrated in five-to-nine-year-olds, according to data by the CDC.

“There is probably something about the infants’ immune system that may not predispose them to post-infectious inflammatory conditions like these,” says Mithal. Experts are still trying to figure out why some kids are affected and not others, and there are reports of babies with the syndrome. But, once again, it seems that infants’ immune systems are especially equipped to dodge the novel coronavirus’ threats.