Serological binding and functional responses to COVID-19 vaccination in children with a history of MIS-C.


In a recent study published in medRxiv* Preprint server A team of researchers evaluated serologic responses to coronavirus disease 2019 (COVID-19) vaccines in children who developed multisystem inflammatory syndrome (MIS-C) following previous infection with severe acute respiratory syndrome coronavirus 2 (SARS). -CoV-2) infection.

Study: Serological responses to vaccination against COVID-19 in children with a history of multisystem inflammatory syndrome (MIS-C).  Image credit: ezps/Shutterstock
Stady: Serological responses to COVID-19 vaccination in children with a history of MIS-C. Image credit: ezps/Shutterstock

background

Multisystem inflammatory syndrome is a dysregulated immune response that develops in children after infection with SARS-CoV-2. It is an inflammatory syndrome characterized by involvement of multiple organs, myocardial infarction, and sometimes death. Some studies have found that MIS-C is associated with a strong serological response during SARS-CoV-2 infection. However, a decrease in antibody titers was observed within three months, but the potential for reinfection or recurrence of MIS-C is unknown.

The US Centers for Disease Control and Prevention has approved the COVID-19 vaccination for children who had MIS-C previously, but at least 90 days after the onset of MIS-C symptoms. Given the unclear pathophysiology of MIS-C and potential relationship with serologic responses to SARS-CoV-2 infection, it is important to evaluate serologic responses evoked by COVID-19 vaccines in children previously given MIS-C.

about studying

In this study, the researchers enrolled hospitalized children with MIS-C, those with positive polymerase chain reaction (PCR) tests for symptoms of COVID-19, and healthy children as controls. Blood samples were collected for plasma and serum isolation.

For follow-up, children in the hospital were invited to provide blood samples at one, three, six and 12 months after hospitalization, while other participants were encouraged to provide samples before and after vaccinations against the coronavirus. Participants who had at least one sample after the second dose of BNT162b2 vaccine were finally included in the study.

Immunoglobulin G-binding (IgG) was measured against SARS-CoV-2 spike protein from the Wuhan-Hu-1 wild-type strain, Alpha, Beta, Delta, Gamma and Omicron variants. Enzyme-linked immunosorbent assays (ELISA) They were also used to measure IgG antibodies that bind to the binding domain of the wild type receptor and the nuclear glove protein.

Pseudotyped lentivirus particles carrying wild type or sub-omericon Spike Proteins They were used for neutralizing antibody assays. In addition, the researchers used transfected target cells expressing either wildtype or Omicron spike proteins to perform antibody-dependent cell-mediated cytotoxicity (ADCC) assays.

consequences

Results reported that the final cohort of participants consisted of five children hospitalized with MIS-C, five with confirmed COVID-19 virus, and six healthy children in the control group for whom blood samples were available after vaccination against COVID-19. Two children diagnosed with COVID-19 were also hospitalized, requiring admission to the intensive care unit. The MIS-C group, two children with COVID-19, and one of the controls had samples from different time points, which were used for longitudinal analysis.

Antibody titers revealed that all children hospitalized with MIS-C and COVID-19 showed high levels of IgG binding against elevated SARS-CoV-2 proteins from multiple variants, but that titers decreased before COVID-19 vaccination.

Cross-reactive IgG antibodies increased after vaccination and were maintained at high levels for three months after vaccination. The antibody titer increased significantly after each dose of BNT162b2 vaccine. The ELISA results showed that antibodies against the receptor-binding domain also increased after vaccination in all five children hospitalized with MIS-C.

While IgG titers after vaccination and Untruthful neutralizing antibodies Against wild-type spike protein were similar for all three cohorts, IgG antibodies bound to the Omicron sub-variant spike proteins were 2- to 4-fold lower than those against wild-type spike protein for all cohorts, although without a statistically significant difference. Furthermore, the control group showed significantly lower pseudovirus-neutralizing antibodies against the Omicron variant, while the MIS-C and COVID-19 groups showed lower but not statistically significant differences.

Functional ADCC titers against the wildtype strain were significantly elevated in the MIS-C group compared to the control group, but those opposing the Omicron variant were low for all three cohorts. As patients with hybrid immunity from previous SARS-CoV-2 infection and vaccination showed higher ADCC titres, the authors believe that the association of ADCC with protection from reinfection needs further exploration.

conclusions

Overall, the findings reported that cross-reactive antibodies were significantly enhanced in children with a history of MIS-C, and serologic responses were maintained for up to three months after the second dose of BNT162b2 vaccine.

Although post-vaccination IgG, pseudovirus neutralizing antibody, and ADCC titers against wildtype virus were similar for the three cohorts, the pseudovirus neutralizing titer against the Omicron variant was lower for the control group. The two hybrid-immune cohorts (with MIS-C or COVID-19 and vaccines) showed pseudovirus neutralization and ADCC antibody titers against the Omicron variant.

*Important note

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, directing clinical practice/health-related behaviour, or treated as hard information.



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