SARS-CoV-2: Immune response comparison in children and adults

A recent study by researchers at the Irving Medical Center of Columbia University in New York showed distinct variations between the antibody responses of children and adults with COVID-19. The variations in the form, quantity, and neutralizing activity of antibodies were seen in particular.

Father and son
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In slightly different ways, COVID-19 impacts kids and adults. Many of the symptoms in children are similar to those in adults, although the severity of the disease is usually milder in children than in adults.

The majority of children infected with SARS-CoV-2 are asymptomatic or have mild symptoms. There are most commonly cough, fever, or gastrointestinal symptoms.

Children under the age of 1 and children with some underlying medical conditions are at higher risk of developing a serious form of COVID-19.

Children who inherit COVID-19 have a medical disorder called multisystem inflammatory syndrome in children (MIS-C) in some unusual instances. Inflammation of the eyes, skin, brain, kidneys, lungs, heart, or gastrointestinal tract is caused by this condition, often starting weeks after the person has contracted SARS-CoV-2.

Adults are more likely to develop serious or critical COVID-19 diseases than children especially older adults or those with certain underlying medical conditions such as obesity, type 2 diabetes, chronic kidney disease, and cancer.

Severe illness also involves hospitalization, and complications such as acute respiratory distress syndrome (ARDS), pneumonia, blood clots, acute kidney injury, sepsis, or cardiomyopathy can include management.

Varying clinical presentation

Scientists do not yet understand why children and adults respond to the SARS-CoV-2 infection so differently.

A recent study examined the differences in immune responses between adults and children to SARS-CoV-2. A number of immune components is investigated by the researchers.

People with SARS-CoV-2 infection and people recovering from mild illness exhibit new coronavirus protein-specific antibodies: spike (S) proteins and nucleocapsid (N) proteins. The virus ‘S protein binds to the receptor of the cell, which enables viral entry. For replication of SARS-CoV-2, the N protein is required.

Anti-S antibodies are able to neutralize viral activity effectively. There are currently studies exploring their use in vaccines and for the treatment of serious COVID-19 disease.

In the new study, which appears in Nature Immunology, researchers investigated the form and neutralizing activity of antibody response seen at the New York-Presbyterian/Columbia University Irving Medical Center hospital and the Morgan Stanley Children’s Hospital of New York from March to June 2020 in a total of 32 adults and 47 children with COVID-19.

Two groups of adults and two groups of children were included in the study. There were 19 convalescent plasma donors (CPD) who recovered from mild COVID-19 respiratory disease without needing hospitalization in one group of adults. Thirteen individuals who were diagnosed with significant COVID-19 ARDS (COVID-ARDS) were in the second adult category.

The children were 3-18 years of age. 16 people who were hospitalized with MIS-C were included in the first group; 31 children with COVID-19 who did not experience MIS-C (non-MIS-C) were in the second group.

Among the pediatric class that was not MIS-C, 48 percent were asymptomatic.

Participants had high levels of inflammatory markers called interleukin 6 and C-reactive protein in both the COVID-ARDS and MIS-C groups. There were also significantly higher levels of ferritin and lactate dehydrogenase in those in the COVID-ARDS group than in those in the MIS-C group.

ARDS was developed by only two children: one in the non-MIS-C and one in the MIS-C category. According to the authors of the study, this highlights the disparity in inflammatory responses and clinical symptoms between adults and children in reaction to COVID-19.

Different antibody responses

Anti-S antibodies were produced by both adult groups: immunoglobulin G (IgG), immunoglobulin M (IgM), and antibodies to immunoglobulin A (IgA). In the COVID-ARDS group, there were significantly higher concentrations of these antibodies.

In comparison, there was a common distribution of anti-S antibodies in the two classes of children and in CPD adults: the predominance of IgG and low levels of anti-S IgM.

The amount of anti-N IgG antibodies in the two groups of children was significantly lower than in both groups of adults. These findings indicate that concentrations of anti-N antibodies depend on age and not on symptoms.

Compared with the two adult groups, the findings showed substantially lower neutralizing behavior in the two pediatric groups. There were no variations between the two pediatric groups in neutralizing behavior, but the adult COVID-ARDS group exhibited the highest neutralizing potency in all four groups.

Reason for differences

These findings demonstrate substantial differences between adults and children in the quantity and specific antibodies developed in response to different grades of SARS-CoV-2 infection.

In infants, COVID-19 antibody responses were mainly anti-S IgG antibodies and had the lowest degree of neutralizing activity.

Related antibody patterns, neutralizing activity, and concentrations were seen in pediatric patients affected with different severities of COVID-19. In adult groups, the highest concentration and variety of anti-SARS-CoV-2 antibodies with the highest neutralizing activity occurred in patients with the most extreme disease (ARDS).

This is a new infection for all, but for the first time children are uniquely adapted to seeing pathogens. That’s what they are supposed to do with their immune system. Children have a lot of naive T cells that can identify all kinds of new pathogens, while our immunological memories are more focused on older people. “We’re not as capable of reacting as kids can to a new pathogen,” explains study co-lead Donna Farber, Ph.D.

Since the children’s immune system effectively clears the virus, relative to adults, this could result in decreased functional antibody response. Viral clearance variations may also explain why children typically experience less serious COVID-19 disease.

A milder course of illness in children is also associated with lower anti-N antibody concentrations. This is because only after the destruction of cells that are infected by SARS-CoV-2 are N proteins released.

“There is a correlation between the severity of the immune response and the magnitude of the infection, according to Farber: the more serious the infection, the more robust the immune response, since more immune cells and immune reactions are required to clear up a higher dose of a pathogen.”

Children can also develop a more powerful innate immune response than adults to SARS-CoV-2. Interferon, which interferes with viral replication, and macrophages, which swallow and digest viruses, are released by the innate immune response.

“If the innate response is really strong, Farber adds, that can decrease the viral load in the lungs, and the adaptive response antibodies and T cells have less to clean up.”

In addition, children will develop less angiotensin-converting enzyme 2 (ACE2) receptors than adults in the cells lining their airways. On human cell surfaces, ACE2 is a protein by which SARS-CoV-2 gains entry into the cells.

“We still have very little knowledge about all these problems,” says co-lead author Matteo Porotto, Ph.D. “The relationship between the virus and the host is why we see so much diversity in responses to this virus, but we do not yet understand enough about this virus to really decide what leads to serious disease and what leads to mild disease.”

In order to understand how illness or defense occurs in response to exposure to SARS-CoV-2, further studies are needed to identify differences in adult and pediatric immune responses to COVID-19. The advancement of age-related testing and safety to control this unrelenting pandemic may have a profound effect on these findings.

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