Multisystem inflammatory syndrome in children (MIS-C) is a severe manifestation of SARS-CoV-2 in children and adolescents.1 Our objective was to estimate the risk of MIS-C after SARS-CoV-2 infection in vaccinated people. and not vaccinated during the Omicron wave. Furthermore, we aimed to compare the risk and clinical characteristics of MIS-C with pre-Omicron waves.
Methods
This population-based cohort study prospectively included patients aged 0 to 17 years with MIS-C from all 18 Danish pediatric departments. Patients were diagnosed from January 1, 2022 to March 15, 2022, after SARS-CoV-2 infection between January 1 and February 1, 2022, when Omicron made up more than 95% of the variants . We followed STROBE reporting guidelines for cohort studies. We used previously reported data to compare MIS-C during Omicron with pre-Omicron waves.1,2
We calculated the risk of MIS-C per 1 million estimated SARS-CoV-2 infections in children and adolescents. We estimated the number of infections by applying multipliers of 1.5 to 2.1 to laboratory-confirmed infections obtained from Danish COVID-19 surveillance registries.
All 95% CIs were calculated using an exact method for binomial proportions. We compared the risks of MIS-C in risk ratios (RR) using Fisher’s exact test.
Two-tailed Mann-Whitney U or χ2 tests were used to compare patient characteristics. Permission to release patient data was obtained through oral and written parental consent or a waiver of the requirement.
Results
We identified 1 vaccinated and 11 unvaccinated patients with MIS-C among estimated 583,618 infected children and adolescents, including 267,086 vaccinated individuals. There were no cases of MIS-C among the estimated 31,516 people with reinfections.
During the Omicron wave, the risk of MIS-C after SARS-CoV-2 infection was significantly lower among vaccinated versus unvaccinated individuals (RR, 0.11; 95% CI, 0.01- 0.83; P = 0.007).
The risk of MIS-C among unvaccinated persons during the Omicron wave was significantly lower than during the Delta wave (RR, 0.12; 95% CI, 0.06-0.23; P < .001) and wild-type wave (RR, 0.14; 95% CI, 0.07-0.29; p < 0.001). The phenotype of MIS-C was similar in the Omicron and pre-Omicron waves.
Discussion
We found that the risk of MIS-C following SARS-CoV-2 infection during the Omicron wave is substantially lower compared to previous SARS-CoV-2 variants. This could be explained by a reduced ability of Omicron to trigger hyperinflammation , as it is phylogenetically different and associated with increased immune escape. individuals had confirmed reinfection, and such a reduced risk after reinfection has not yet been reported.
The risk of MIS-C during the Omicron wave was found to be significantly lower after infection in vaccinated compared to unvaccinated children and adolescents.
A high effectiveness of the vaccine against MIS-C was previously found during the Delta wave, mainly explained by a high effectiveness against the Delta variant.
The present study suggests a direct effectiveness of the MIS-C vaccine after advanced infection. This may be due to vaccine-induced modulation of the immune system that makes it less likely to cause hyperinflammation after SARS-CoV-2 infection.
The main limitation of this study was the small population size that resulted in few cases of MIS-C, making our estimates vulnerable to fluctuations. The multipliers of 1.5 to 2.1 used to estimate the actual number of infected people were fraught with uncertainty and were lower than those previously used for the US population; our multipliers were low due to extensive testing capacity in Denmark with fortnightly screening tests in schools.
In this Danish population-based cohort study, we found a substantial decreased risk of MIS-C after infection with Omicron compared to pre-Omicron variants and a lower risk of MIS-C after intercurrent infections in individuals vaccinated .
