COVID-19 Vaccination Significantly Reduces Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) in California

Introduction

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition that can develop in children following infection with SARS-CoV-2, the virus that causes COVID-19. Characterized by widespread inflammation affecting multiple organ systems, MIS-C can lead to symptoms such as fever, abdominal pain, rash, and low blood pressure. In severe cases, it can be life-threatening, requiring hospitalization and intensive care.

This article examines findings from a study conducted by researchers from the California Department of Public Health (CDPH), which investigated the incidence of MIS-C among vaccinated and unvaccinated children aged 5 to 17 years in California. By analyzing vaccination status, researchers aimed to understand the protective effect of the Pfizer-BioNTech COVID-19 vaccine against MIS-C. The study, covering cases from January 2021 to June 2022, provides new insights into how vaccination may mitigate risks associated with post-COVID complications in children.

Study Design and Methodology

The study included California children who met the Centers for Disease Control and Prevention (CDC) criteria for MIS-C. Researchers collected data through the California Reportable Disease Information Exchange (CalREDIE), which involved clinical records, vaccination histories, and demographic information, such as race and ethnicity. Vaccination status was determined via the California Immunization Registry and other regional immunization data systems.

The study compared MIS-C incidence in fully vaccinated children, partially vaccinated children, and unvaccinated children within two age groups: 5–11 and 12–17. A child was considered fully vaccinated if the MIS-C episode occurred at least 14 days after completing the Pfizer-BioNTech vaccine series. Those with one dose or less than 14 days since their last dose were categorized as partially vaccinated.

Statistical Analysis

The researchers calculated incidence rate ratios (IRR) to compare the relative risk of MIS-C in vaccinated versus unvaccinated children, adjusting for population estimates. Statistical analyses were conducted using R software, with significance set at a p-value of 0.05.

Results: MIS-C Incidence by Vaccination Status

The study included 138 MIS-C cases in total, with a striking difference in MIS-C incidence based on vaccination status across both age groups:

• In the 5–11 age group, 51 of 60 cases (85%) occurred in unvaccinated children. The IRR for unvaccinated children was 3.3 times higher than for fully vaccinated children (95% CI: 1.6–6.7, p = 0.0004).
• In the 12–17 age group, 66 of 73 cases (90%) occurred among unvaccinated children. The IRR in unvaccinated children was 22.9 times higher compared to their fully vaccinated peers (95% CI: 10.5–49.8, p < 0.0001).

These results indicate that COVID-19 vaccination, particularly full vaccination, is associated with a significant reduction in MIS-C risk across both age groups. Notably, when partially vaccinated children were grouped with fully vaccinated children, the relative protection persisted, though to a lesser extent.

Severity of MIS-C by Vaccination Status

The study found that all MIS-C-related fatalities (n=4) occurred among unvaccinated children. Additionally, among the 5–11-year-olds, only unvaccinated children experienced MIS-C cases involving six or more organ systems (p = 0.04), indicating that unvaccinated children not only had a higher incidence but also more severe MIS-C outcomes. However, the small sample size of severe cases limited further statistical interpretation of this finding.

Discussion: The Impact of Vaccination on MIS-C Risk

The findings of this study align with previous research from the United States, Denmark, and France, all of which showed a reduced risk of MIS-C among vaccinated children. The results highlight that vaccination provides substantial protection against MIS-C, particularly in the 12–17 age group, where the incidence rate was notably higher among unvaccinated children.

This protective effect of vaccination against MIS-C may stem from the reduced likelihood of severe SARS-CoV-2 infection in vaccinated children. By mitigating the severity of initial COVID-19 infection, the immune response that leads to MIS-C may be less likely to occur or be less intense, resulting in fewer cases and milder outcomes among vaccinated individuals.

The finding that MIS-C cases involving multiple organ systems or fatalities occurred exclusively in unvaccinated children suggests that vaccination could play a critical role in preventing the most severe MIS-C presentations. However, due to the limited sample of vaccinated children with MIS-C, further studies with larger cohorts are necessary to confirm this protective effect.

Public Health Implications and Recommendations

This study reinforces the importance of COVID-19 vaccination for children as a measure to prevent severe complications like MIS-C. Public health recommendations for pediatric vaccination can leverage this evidence to address vaccine hesitancy by demonstrating the role of vaccination in preventing not only acute COVID-19 but also severe post-infectious syndromes.

Additionally, public health officials might consider strategies to ensure equitable vaccine access across different demographics. The study found variations in MIS-C incidence based on gender and race/ethnicity, which reflect broader patterns in vaccine uptake. Targeted vaccination campaigns and educational outreach may help increase vaccine uptake in underrepresented populations, reducing disparities in vaccine protection. As always, supplemental spread reduction (mask wearing, for instance) is a continued good practice.

Limitations and Areas for Future Research

While the study provides valuable insights, it also has limitations. First, the relatively small sample size of MIS-C cases, especially among vaccinated children, may limit the generalizability of the findings. Additionally, the reliance on passive surveillance and self-reported data might introduce underreporting or reporting biases, as less severe MIS-C cases could go unnoticed. This should not be seen as discrediting the study, however, as almost any study on this topic is likely to encounter these issues.

Another limitation is the lack of variant-specific data. While most cases occurred during the Delta and Omicron variant waves in California, the study could not directly attribute MIS-C risk to specific SARS-CoV-2 variants. Future research could aim to include variant-specific analyses to assess whether certain variants are more likely to lead to MIS-C in vaccinated versus unvaccinated children.

Finally, while the study focused on the Pfizer-BioNTech vaccine, additional research into other vaccines, including the Moderna vaccine, could further clarify the comparative effectiveness of different COVID-19 vaccines in preventing MIS-C. This could also further support work in helping vaccine hesitant populations gain trust in COVID-19 vaccines.

Conclusion

The California Department of Public Health’s study underscores the significant protective effect of COVID-19 vaccination against MIS-C in children, particularly among older age groups. With a reduced risk of severe outcomes and fatalities among vaccinated children, the findings provide strong support for public health efforts to increase COVID-19 vaccine uptake in pediatric populations.

These results add to the growing body of evidence that vaccination not only prevents COVID-19 infection but also mitigates its most severe pediatric complications. Public health campaigns focused on increasing vaccination rates could help further reduce the incidence and severity of MIS-C, improving overall child health outcomes in the face of ongoing COVID-19 challenges.

The image for this article is gathered from FMT.