The risk of severe COVID-19 increases with age. According to Harvard Medical School, 80% of COVID-19 hospitalizations are in people over 65. These patients have a 23 times higher risk of death than those younger than 65 years of age. Moreover, the risk of hospitalization and death in people over 65 is 1000-8000 times higher than those from 0 to 17 years.
The older a person is, the more likely to find comorbid conditions like cardiovascular disease and obesity. These diseases contribute to the more severe course of the coronavirus. However, this cannot explain why SARS-CoV-2 infection is milder and even asymptomatic in children and young people.
British scientists investigated serological (antibodies) and cellular (T-cell) immune responses to SARS-CoV-2 in a cohort of 91 children and 154 adults with mild and asymptomatic infections – one of the largest cohorts studied to date. Scientists have found that children develop robust cross-reactive immune responses to SARS-CoV-2:
- Spike-specific T-cell responses were more than twice as high in children and found in many seronegative children. These immune responses are a consequence of prior exposure to pre-pandemic cold-related coronaviruses (HCoV) and are exacerbated by SARS-CoV-2 infection.
- Children retained antibodies and cellular responses six months after infection, while immunity declined in adults. Spike-specific responses in children persisted for over 12 months.
Although SARS-CoV-2 is a novel coronavirus, most people have been exposed to the common cold coronaviruses throughout their lives, which trigger humoral, B-cell, and T-cell immune responses. Coronaviruses HKU1 and OC43 are genetically similar to SARS-CoV-2. Adaptive immune responses to these coronaviruses also respond to SARS-CoV-2 proteins, including the spike protein.
Scientists at Boston University School of Medicine in the United States have found that recent infections with the common cold coronaviruses are associated with a decrease in the severity of COVID-19. Scientists have suggested that immune responses to recent cold-based coronaviruses may protect against severe COVID-19.
However, in another study, American scientists came to the opposite conclusion. Some people had cross-reactive antibodies against SARS-CoV-2 before the pandemic. However, these antibodies did not protect against SARS-CoV-2. When infected with SARS-CoV-2, the level of cross-reactive antibodies increased.
In a study of a large cohort of children and adults with mild and asymptomatic COVID-19, British scientists found that humoral and cellular immune responses differed in children aged 3-11 compared to adults aged 20-71.
Antibody Responses In Children And Adults
Children and adults infected with SARS-CoV-2 can develop robust antibody responses against the receptor-binding domain (RBD), viral genome coat protein (N), and SARS-CoV-2 spike protein (S).
Compared to adults, children more intensely produced antibodies to the spike protein.
Antibodies against common cold coronaviruses have been found in children and adults who are seropositive for SARS-CoV-2. The levels of these antibodies were increased compared to the seronegative control group.
Antibody levels against all four HCoVs were most increased in SARS-CoV-2 seropositive children, especially for HKU-1 and OC43.
No significant changes were found in antibody titers against unrelated respiratory viruses – influenza A and respiratory syncytial viruses. It suggests that this effect was specific to HCoV.
These data indicate that SARS-CoV-2 infection in children significantly enhances preexisting immunity to OC43 and HKU-1. It explains the higher titer of antibodies to SARS-CoV-2 in children. Antibodies to OC43 and HKU-1 in children predominantly cross-react with the S2 fragment of the SARS-CoV-2 spike protein.
The humoral immune response to the spike protein in children persists for more than 12 months after infection with SARS-CoV-2, and the level of antibodies is higher than in adults.
There is a better binding of antibodies to the spike protein of new coronavirus strains in children. However, the ability to neutralize the virus is the same in adults and children.
T-Cell Responses In Children And Adults
After infection with SARS-CoV-2, children developed a stable cellular immune response to spike protein. The number of cross-reactive T cells in children was twice as large as in adults. A decrease in the number of cross-reactive T cells in adults may worsen SARS-CoV-2 infection. CD8+ T cells make up a large part of the repertoire of spike-specific T cells in children.
Conclusions
CD4+ T cells, CD8+ T cells and antibodies (neutralizing and non-neutralizing) collectively control SARS-CoV-2 infection.
In addition to producing antibodies to the S1 portion of the coronavirus spike protein, SARS-CoV-2 vaccines elicit cross-reactive T cell and antibody responses targeting S2.
In natural infection, antibodies in children predominantly target conserved proteins common to HCoV and SARS-CoV-2 spines, especially S2.
Developing a new generation of coronavirus S2-based vaccines could provide enhanced protection.
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Reference
Boosted immunity to the common cold might protect children from COVID-19
