Bali Pulendran, a professor of microbiology, immunology, and pathology at Stanford University, has researched a mystery unique to COVID-19 for two years.
“For almost every infectious disease, the most vulnerable populations are at the extremes of age—the very young and the very old,” he once said. “But with COVID-19, the young are spared.”
Children Are Different
Children are not mini-adults. Depending on their age, they can have similar or very different responses to infectious diseases.In the case of COVID-19, children generally experience a milder form of the disease.
“It’s an interesting question that no one has fully answered,” said Dr. Cody Meissner, a professor of pediatrics at Dartmouth College’s Geisel School of Medicine, in an interview with The Epoch Times. “Several theories have been put forward to try and explain this.”
The primary reason is that children have a faster innate immune system, often referred to as the first line of defense, compared to adults. This enables them to mount a robust defense against respiratory infections more quickly.
Another explanation is that children are more susceptible to respiratory infections, and some of these prior infections may provide them with a degree of immune protection against COVID-19.
Anatomically speaking, children not fully grown are at a disadvantage when exposed to respiratory diseases. They have smaller airway diameters, meaning more severe symptoms when the airways get inflamed or have mucus build up.
They also have a smaller lung capacity, making them more prone to hypoxia with respiratory infection, professor of immunology Kenneth Rosenthal, PhD, told The Epoch Times.
However, compared to adults, children have been found to have higher levels of innate immune cells in the nose, which can help eliminate viruses early on.
Strong Innate Immunity
While children tend to have a fast and robust innate immune response, studies have found that most adults who experience severe COVID-19 tend to have an impaired innate immune response.The innate immune response is the immune system we inherit when born.
“[The immune response is] always there and ready to respond to microbes and triggers on the fly,” Mr. Rosenthal explained. In contrast, the adaptive immune system, which is more developed in adults, can generate more memorized, targeted immunity. However, it is slower to respond and can take days to activate.
This is not to say that children do not have an adaptive immune response. But since this type of immunity is built up by experiences with viruses and other pathogens, children tend to have accumulated less immunological memory than adults.
Vaccination is primarily used to bolster adaptive immunity while children are young.
“A large proportion of adult men prone to more serious COVID have antibodies to interferon,” Mr. Rosenthal said. Consequently, they cannot mount the initial innate response, though scientists do not know why some adults form these antibodies.
The infection progresses unhindered while the immune system attempts to restrain the extensive infection, which could “lead to problematic outcomes,” he added.
This can cause full-blown inflammatory responses.
Less Prone to Inflammatory Storm
A significant risk factor for severe COVID-19 is the inflammatory cytokine storm caused by excessive levels of cytokines in the body.During an infection, immune cells release cytokines to help activate and coordinate other immune cells. There is always some presence of them in the body.
When the immune system fails to control the infection, and viruses replicate, immune cells dispatch more cytokines as a warning. These cytokines then activate more immune cells, causing intense inflammation, which can lead to tissue damage, organ failure, and eventually death.
Adults are more prone to cytokine storms because they tend to have more cytokines in the blood, meant to protect their bodies against daily assaults. These include smoke, toxic particles, toxic foods, and certain bacteria that live in our gut, on our skin, or elsewhere, Mr. Rosenthal said. The necessary protective responses produce inflammatory cytokines “on an everyday, routine basis.”
Children, however, have lower baseline cytokine levels due to fewer exposures to environmental and pathogenic assaults. Plus, they generally have healthier constitutions with fewer chronic diseases and unhealthy habits.
Even in the rare case of children developing severe COVID-19, which often presents as multisystem inflammatory syndrome in children (MIS-C), most children quickly recover without any persistent symptoms.
The Enigma of Mild COVID in Infants
While mild COVID-19 in children and adolescents can be explained away by their fast innate immune systems and generally healthier constitutions, this explanation fails concerning infants and toddlers.“It’s one of the great mysteries of human immunology,” Mr. Pulendran told The Epoch Times.
Infants are typically born with immature innate and adaptive immune systems with weaker constitutions, making them more susceptible to infections. Premature infants are even more vulnerable.
Children under the age of 2 have a much higher chance of dying from respiratory diseases like respiratory syncytial virus (RSV) and influenza than older children and adults under age 50.
In general, infants “do not have any prior immune history and, therefore, no antibodies or T-cell memory to rapidly respond to the challenge,” Mr. Rosenthal said. They also have very few innate immune cells at birth. By the second month of life, they should accumulate enough innate immune cells to overcome this vulnerability.
Full maturation of the immune system occurs in the first seven to eight years of life.
Dehydration is also a deadly factor in infected children and infants due to their higher metabolic rates and reduced water reserves compared to adults.
Yet to researchers’ amazement, infants were largely left unscathed during the COVID pandemic.
“We were desperate to find kids with severe symptoms [for our study],” Mr. Pulendran said. “We asked our Cincinnati Children’s collaborators to please send us samples of kids with severe disease. Try as they might, they couldn’t find samples from kids with severe infection in all the four years they were collecting them.”
After natural infection, adults tended to summon fast yet short-lasting antibodies against COVID-19, with antibody levels declining by 10-fold in six months. Infants, on the other hand, had a slower but steadier antibody response. Their antibody levels never dropped and either plateaued or kept rising throughout the 300 days of the study, eventually rivaling those of adults at their peak.
While adults tended to see an increase in inflammation-promoting proteins in the blood even after a mild COVID-19 infection, this rise was not seen in infants. Infections and inflammatory markers in the blood can be severe, as they may lead to systemic inflammatory reactions.
Instead, the researchers found that in infants’ and children’s noses, “we saw plenty of these very inflammation-promoting proteins,” Mr. Pulendran said. Unlike blood, the nose is a relatively more localized area, and having more inflammation-promoting proteins can help reduce the viral load as it invades.
“The virus may be getting nipped in the bud in the nasal tracts,” Mr. Pulendran said.
“So [children are] activating the immune system in the nose to contain that virus, and then their body is not as reactive, which is a good way to respond to the virus without causing more systemic disease,” Dr. Yonker said.
Do Children Have an Advantage Over Adults?
This depends on the age range, but children tend to have a survival advantage compared to adults regarding newly encountered viral diseases.“It’s true for lots of viral infections like measles and chickenpox,” Dr. Meissner explained. “That’s why children used to have chickenpox parties before there was a vaccine.” Parents would host parties and invite uninfected children, ensuring their children would contract chickenpox when they’re younger, knowing the disease is more severe if contracted in adulthood. We now understand these parties are not a wise decision because vaccines are a much safer means of inducing protective immunity, he said.
An exception to this trend is the Epstein-Barr virus (EBV), which can cause a debilitating syndrome in teenagers and adults. However, in infected children, EBV mainly causes a sore throat.
However, Mr. Rosenthal highlighted that the adaptive immune system, which is more developed in adults, helps control infections that evade innate immunity.
“Progressing into adulthood, we face tuberculosis, fungi, viral infections, and cancers that require antigen-specific immune control ... If there is immune memory after the first exposure, it promotes a rapid protection.”
The usual trend is that adults are less capable of responding promptly to new infections after puberty but have robust immune responses against previously encountered infections.
“We’re constantly developing this protective response that serves us down the road, so that is probably part of the trade-off. The biggest problem would be having a brand-new virus out of nowhere that we hadn’t had the chance to really build a response to,” Dr. Yonker said.
“There’s a goldilocks period, or the golden age of the immune system, that is somewhere in between the two extremes of age,” Mr. Pulendran said.
“I’m not so sure that we could be so precise as to say that the immune system is at its peak at puberty, but there’s a middle age somewhere, and I would say it’s at around, maybe 12 or 13, and growing to about 30 or so, in which really the immune system could be described as what you might say is at its peak.”
During immunosenescence, the thymus, which produces adaptive T cells, becomes less active and starts to shrink.
Adaptive immune cells are similarly affected. Immune memory cells increase with age, supplying long-term protection against pathogens one has already encountered. However, naive T and B cells decline, meaning there are fewer in reserve for the formation of new memory cells when a person is exposed to newer pathogens.
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