Why do children have less severe COVID-19 than adults?

A: A better innate immune response may explain milder COVID-19 disease in kids, but they still CAN and DO get infected and transmit SARS-CoV-2, especially the more transmissible Delta variant.

👉🏽 TL;DR. Children have fewer ACE2 receptors, a more robust innate immune system, and produce more anti-viral proteins (like type 1 interferons) than adults. These differences in the immune response to SARS-CoV-2 may explain why children are less likely to have symptomatic disease. However, children get infected, transmit the virus, and may develop long term complications of COVID-19.

Recent data shows that COVID-19 infections in children in the U.S are climbing rapidly. It is imperative that those who are eligible get vaccinated in order to protect our children, particularly young children and babies who are not yet eligible to receive a COVID-19 vaccine.

Children appear to be able to fight the SARS-CoV-2 virus much more easily than adults, and often recover relatively quickly from mild cold or cough symptoms. Of all the bad news during the pandemic, this fact has been a huge relief to many. There are several hypotheses for the the milder course of disease in children:

1. Fewer ACE2 receptors. The ACE2 receptor is the protein that SARS-CoV-2 attaches to through its spike protein in order to enter a cell. In one study researchers examined tissue from nasal passages in patients between the ages of 4 and 60. They found that ACE2 receptors are much less abundant in children (especially children less than 10 years of age) when compared with adults. These findings suggest that children may be less likely to get infected with SARS-CoV-2 because they have fewer entry points for the virus (see LINK to reference below).

2. A stronger innate immune response: The immune system is made up of two arms – the ‘innate’ immune system (our first line of defense), and the ‘adaptive’ immune system (second line of defense that kicks in when the innate immune system cannot clear infection). Children have an active innate immune system that can mount a rapid response against viral infections (see LINK to reference below). In children, innate immune cells and proteins that can recognize viruses (virus-sensing proteins) are readily available in nasal tissue, whereas in adults, virus-sensing proteins have to first be made before they can activate immune cells. Therefore, the innate immune response in children is much quicker and much more readily available to clear viral infection.

3. A stronger type 1 interferon response: Cells are equipped with virus-sensing proteins. One such protein is called ‘MDA5’ – when MDA5 senses a virus, it instructs the cell to produce a group of proteins called ‘type 1 interferons’, that are highly effective in clearing viral infection. Recent research has shown that children make more MDA5, so can make more type 1 interferons and combat SARS-CoV-2 infection much more effectively than adults. People who have genetic defects that affect their ability to make type 1 interferons are much more susceptible to severe COVID-19.

So while we might conclude that children won’t get sick, this is NOT the case. Since the summer of 2021, COVID-19 infections in children have risen sharply, increasing almost 10-fold from the spring of 2020 to a staggering 226,000 confirmed cases last week in the U.S. (9/16/21). This higher absolute number of infections in kids is due to the more infectious Delta variant as well as a return to more normal activities and social contacts. The increase in the *relative* share of infections happening in kids compared to other ages is due to more vaccine protection in adults. Children now represent close to 26% of COVID-19 cases in the US.

➡️ But children only get “mild” COVID-19 and I shouldn’t worry, right?

NO, children can still get pretty sick. While most children recover from a mild case of COVID-19, a few have fallen very ill, generally about a month later, with a rare, life-threatening condition called ‘MIS-C’. MIS-C stands for ‘Multisystem Inflammatory Syndrome in Children’. As the name implies, these children developed inflammation of multiple organs, some developed blood clots, or dangerously low blood pressure. A review of data from 26 countries reported a 0.14% incidence of MIS-C in children with confirmed SARS-CoV-2 infection. However, the actual incidence may be different as the number of SARS-CoV-2 infections in children is likely underestimated (see LINK to reference below). Although less frequent than in adults, long COVID symptoms have also been documented in children (see LINK to reference below). And as of last week, 516 children in the U.S. have died from COVID-19.

➡️ Because of all these risks, we SHOULD STILL take actions to protect children from COVID-19. The best protection is for YOU and those around children to get vaccinated. Children aged 12-17 CAN get vaccinated. Children ages 5-11 may be eligible soon (yay!), making our mitigation measures such as masks, ventilation, and testing even more important in the meantime. For our youngest children who may still wait for approved vaccines, creating a ring of vaccination protection around them is the best strategy.
Stay safe! Get vaccinated!

Love,
Those Nerdy Girls

📚 Further reading:

ACE2 receptors in children and adults:

Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults

Why COVID-19 may be less common in children than adults

Children have stronger innate immune responses:

Unraveling the Mystery of Why Children Are Better Protected from COVID Than Adults

How kids’ immune systems can evade COVID

Rising COVID-19 cases in children:

CDC: Delta variant causing increase in pediatric COVID-19 cases, not severity

Children and COVID-19: State-Level Data Report

COVID19 and MIS-C: