The binding and functional serologic responses to COVID-19 vaccination in children with history of MIS-C

In a recent study posted to the medRxiv* preprint server, a team of researchers evaluated the serological responses elicited by coronavirus disease 2019 (COVID-19) vaccinations in children who developed multisystem inflammatory syndrome (MIS-C) following a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Study: Serologic Responses to COVID-19 Vaccination in Children with History of Multisystem Inflammatory Syndrome (MIS-C). Image Credit: ezps/Shutterstock
Study: Serologic Responses to COVID-19 Vaccination in Children with History of Multisystem Inflammatory Syndrome (MIS-C). Image Credit: ezps/Shutterstock

Background

Multisystem inflammatory syndrome is considered a dysregulated immune response that develops in children after infection with SARS-CoV-2. It is an inflammatory syndrome characterized by the 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 infections. However, the antibody titers have been seen to decrease in three months, but the probability of reinfection or MIS-C recurrence is unknown.

The United States Centers for Disease Control and Prevention has approved the COVID-19 vaccination for children with previous MIS-C, but only after a minimum of 90 days after the onset of MIS-C symptoms. Given the unclear pathophysiology of MIS-C and the potential correlation with serological responses to SARS-CoV-2 infections, it is important to evaluate the serological responses elicited by COVID-19 vaccines in children who have previously had MIS-C.

About the study

In the present study, the researchers enrolled children hospitalized with MIS-C, those who had positive polymerase chain reaction (PCR) tests for symptomatic COVID-19, and healthy children as controls. Blood samples were collected to isolate plasma and serum.

For the follow-up, the hospitalized children were invited to provide blood samples one, three, six, and 12 months after hospitalization, while the other participants were encouraged to provide samples before and after the COVID-19 vaccinations. Only the participants with at least one sample after the second dose of the BNT162b2 vaccine were finally included in the study.

The binding immunoglobulin G (IgG) against the SARS-CoV-2 spike protein from the wildtype strain Wuhan-Hu-1, and the Alpha, Beta, Delta, Gamma, and Omicron variants were measured. Enzyme-linked immunosorbent assays (ELISA) were also used to measure the IgG antibodies that bind to the wildtype receptor binding domain and nucleocapsid protein.

Pseudotyped lentiviral particles carrying the wildtype or Omicron subvariant spike proteins were used for neutralizing antibody assays. Additionally, the researchers used transfected target cells that expressed either the wildtype or Omicron spike proteins to perform antibody-dependent cell-mediated cytotoxicity (ADCC) assays.

Results

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

The antibody titers revealed that all the children hospitalized with MIS-C and COVID-19 exhibited elevated binding IgG levels against the SARS-CoV-2 spike proteins from multiple variants, but the titers decreased before the COVID-19 vaccination.

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

While the post-vaccination IgG titers and pseudovirus neutralizing antibodies against the wildtype spike protein were similar for all three cohorts, the binding IgG antibodies against the Omicron sub-variant spike proteins were two to four-fold lower as compared to those against the wildtype spike protein for all the cohorts, albeit with no statistically significant difference. Furthermore, the control group exhibited significantly lower pseudovirus-neutralizing antibodies against the Omicron variant, while the MIS-C and COVID-19 cohorts showed lower but not statistically significant differences.

The functional ADCC titers against the wildtype strain were significantly elevated in the MIS-C cohort compared to the control cohort, but those against the Omicron variant were low for all three cohorts. Since patients with hybrid immunity from previous SARS-CoV-2 infections and vaccination showed higher ADCC titers, the authors believe that the association of ADCC with protection against reinfections needs to be explored further.

Conclusions

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

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

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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