Children with pre-existing cold immunity have better protection against COVID-19

In the recent issue of Natural immunology, the researchers shared a comprehensive brief on the latest research conducted by Dowell and colleagues. New data from Dowell and the team shows that, compared to adults, children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially activate pre-existing acquired immunity against common cold coronaviruses. that cross-react with SARS. CoV-2 and protect them from serious diseases.

The team suggests that these superior immune responses are derived from previous exposures to HCoV and demonstrate that they are upregulated by infection with SARS-CoV-2.

To study: Strengthened immunity to colds could protect children from COVID-19. Image Credit: Dragana Gordic / Shutterstock

Previous studies have shown that an individual’s biological age is the primary risk factor associated with the development of severe coronavirus 2019 (COVID-19). As of October 27, 2021, nearly 76% of the ~ 737,000 cumulative deaths in the United States were in the elderly, aged 65 or older. Notably, the rate of hospitalization or death from COVID-19 in this age group is approximately 1,000 to 8,000 times higher than in the younger age group 0-17 years. In another study, mortality from SARS-CoV-2 was lowest in children aged 5 to 9 years. However, the answer to why SARS-CoV-2 infection tends to be more mild or asymptomatic in children and youth has yet to be explained.

Fund

SARS-CoV-2 is a novel coronavirus for the human population, however, most people throughout their lives have been exposed to or infected with other antigenically related seasonal cold coronaviruses (HCoVs) and have developed immunity. acquired detectable against them. HKU1 and OC43 are two closely related HCoVs that share extensive sequence homology with SARS-CoV-2. Few studies have shown cross-reactivity of the adaptive immune response to these viruses with SARS-CoV-2 antigens. Another report suggested that recent HCoV infections are associated with a reduction in the severity of COVID-19, however, some reports have even drawn conclusions to the contrary.

Dowell and the team aimed this study to find the immunological relationship between pre-existing responses to endemic HCoV and SARS-CoV-2, and to understand how such cross-reactivity would affect disease outcomes in different age groups.

The study looked at a cohort of 91 children and 154 adults, who had mild or asymptomatic illness in the UK during the second half of 2020. Their convalescent humoral (antibody) and cellular (T cell) immune responses SARS-CoV-2 were quantitatively profiled. The immune responses to other endemic coronaviruses have also been quantified.

Comparison of humoral immune responses

Children and adults produced robust antibody responses against the receptor binding domain (RBD) of SARS-CoV-2, the N-terminal domain, and the full spike glycoprotein ectodomain, as measured by a multiplex electrochemiluminescence test. Nonetheless, compared to adults, children showed a higher but statistically insignificant trend for overall spike-specific antibody production.

Notably, antibody levels against the four endemic HCoVs were increased in children and adults seropositive for SARS-CoV-2, compared to their respective seronegative groups. Antibody levels were most magnified in children infected with SARS-CoV-2 and reached significance for HKU-1 and OC-43. In contrast, antibody levels against other unrelated cold viruses, namely influenza A virus and respiratory syncytial virus, did not change significantly, showing that the effect was specific to others. HCoV only. This demonstrated that SARS-CoV-2 infection in children specifically and significantly stimulated pre-existing immune responses to HKU-1 and OC-43.

The team demonstrated quantitatively that antibodies spiked against OC43 and HKU1 in HIV-positive children primarily cross-reacted with the SARS-CoV-2 S2 domain, explaining the higher SARS-CoV-2 specific titre in children.

The team also found that children maintained a quantitatively higher and longer lasting spike-specific immune response lasting ≥12 months after infection, compared to adults. These superior humoral immune responses existed for both wild-type SARS-CoV-2 and other variants of concern (VOC). In addition to neutralizing antibodies, children retained relatively longer duration of non-neutralizing antibodies against spike epitopes that might provide protection through Fc-mediated effector functions.

Comparison of immune responses mediated by cellular T cells

In lines similar to antibody responses, children developed stronger cellular immune responses to the spike protein after infection with SARS-CoV-2. The team used an immune absorbing spot bound to the enzyme interferon-γ (IFN-γ) (ELISpot) and overlapping peptide pools resulting from the spike, core, membrane and envelope proteins, and observed that T cell responses were also elicited in SARS-CoV. -2 HIV positive children (33/37) and adults (51/64), however, the number of stain-forming / cross-reactive T cells was double in children, indicating better protection against SARS infection- CoV-2 in children.

The profile of cytokine production by SARS-CoV-2 specific T cells was compared in children and adults using a multianalyte bead test on ELISpot supernatants. Children showed a differential functional response compared to adults and demonstrated that samples from adult donors showed a marked response to interleukin-2 (IL-2). In contrast, IL-2 levels in children were very low and CD8+IL-2TNF+IFN-γ+ T cells made up the majority of the tip specific T cell profile.

Notably, T cell-mediated cellular responses were observed in 60% of HIV negative children, compared to HIV negative adults, in whom this proportion was reduced to 34%.

Implications

The study indicates that in addition to the induction of neutralizing antibodies to the virus directed against S1, vaccines against SARS-CoV-2, if they are designed to induce humoral and cellular immune responses directed against the S2 domain , could provide improved protection in all age groups.

The finding that plasma antibodies in children are preferentially enriched with cross-reacting antibodies directed against conserved epitopes shared between the peak glycoproteins of HCoV and SARS-CoV-2, in particular the S2 subunit, suggests a vital contribution. Cross-reactive antibodies in resolving SARS -Viral CoV-2 infection in children.


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