In Reply We appreciate the comments by Dr Jiang and colleagues regarding our recent Research Letter. 1 In our cohort, 5 of 79 patients (6.3%) during the Delta wave and 5 of 33 patients (15.1%) during the Omicron wave received a second dose of the SARS-CoV-2 vaccine at least 2 weeks prior to hospital admission; none of the vaccinated patients were admitted to intensive care units or required treatment with vasopressors. 1 The incidence rate of MIS-C during the Omicron wave was lower than during both the Delta and Alpha waves. 1 Jiang and colleagues state that receipt of 2 doses of SARS-CoV-2 vaccine "was associated with a lower incidence and more favorable outcomes of MIS-C." However, given that our study was retrospective and included a low number of vaccinated patients, causation cannot be inferred between vaccination status and a lower incidence or favorable outcomes of MIS-C. Other possible explanations for these findings include biological and epidemiological characteristics of the Omicron variant, previous infection with SARS-CoV-2, and improved treatment protocols over time. We cannot address any questions regarding vaccine-related MIS-C because patients in our study 1 did not undergo antinucleocapsid or antispike antibody testing.Several recent studies support vaccine effectiveness against MIS-C. Holm et al 2 and Nygaard et al 3 reported that the risk of MIS-C during the Omicron wave in Denmark was significantly lower in vaccinated compared with unvaccinated children and adolescents. A study from France by Levy et al 4 found that most adolescents who developed MIS-C were eligible for a SARS-CoV-2 vaccine but had not been vaccinated, suggesting that SARS-CoV-2 vaccination was associated with a lower incidence of MIS-C in adolescents. Zambrano et al 5 reported that during the Delta wave, the estimated effectiveness of the SARS-CoV-2 vaccine against MIS-C was 91% and all critically ill patients with MIS-C who required life support (ie, invasive mechanical ventilation, vasoactive infusions, or extracorporeal membrane oxygenation) were unvaccinated. In addition, a multicenter case-control study found that vaccination with 2 doses of SARS-CoV-2 vaccine was associated with reduced likelihood of MIS-C. 6 In light of the existing studies and a number of other published reports, we believe that there is enough evidence to conclude that SARS-CoV-2 vaccination can reduce the incidence and severity of MIS-C.