We read with interest the report of a male adolescent who developed multisystem inflammatory syndrome (MIS-C) after Pfizer-BioNTech COVID-19 vaccination by Chai et al.1 The authors described a 17-year-old boy who developed symptoms five days after vaccination with eventual multiorgan involvement. The short latency between vaccination and symptom onset in this case, however, contrasts with other reported cases of MIS-C, which typically takes at least two weeks to develop in the setting of COVID-19 infection.2 The pathogenesis of MIS-C is likely due to the dysregulation of adaptive immune system after acute infection, which may involve expansion of plasmablasts, extra-follicular B-cell activation and immune-mediated tissue injury. Messenger ribonucleic acid (mRNA) vaccines encode the spike protein, which triggers the immune response leading to host defence. It reasonably follows that MIS-C following either mRNA vaccination or natural infection should exhibit a similar latent interval.

In our opinion, the clinical manifestations in this reported case could be better explained by autoimmune/inflammatory syndrome in response to adjuvants (ASIA). Adjuvants refer to substances included in vaccines that enhance the magnitude and durability of the immune response. The important initial step is the activation of the innate immunity, with systemic inflammatory response manifesting within the first few days (which may be in this case), followed by activation of the adaptive immune response. Adjuvants may result in excessive and dysregulated immune activation, with diverse end-organ manifestations, such as neurological, gastrointestinal, respiratory and cutaneous involvement. Notably, two cases of ASIA have been linked to the Pfizer-BioNTech vaccine, manifesting as autoimmune thyroiditis, with onsets within three days of vaccination.3

We opine that the two reported cases of COVID-19 vaccine-induced MIS-C in the literature, including this case, are more consistent with ASIA rather than MIS-C. As MIS-C and ASIA may present with overlapping clinical features, we propose that a minimum interval of two weeks between vaccination and symptom onset should be included for future proposed cases of vaccine-induced MIS-C.