The first reported case of new-onset mania and psychosis post heterologous bivalent mRNA COVID-19 booster vaccination

We report the first case of new-onset mania and psychosis post heterologous bivalent booster vaccination (corresponding to the 4th mRNA vaccine) in Singapore, to our knowledge. The COVID-19 pandemic has significantly impacted mental health, and studies have shown that COVID-19 infections can be directly or indirectly associated with neuropsychiatric symptoms. While mRNA vaccines are highly effective in preventing severe illness and death from COVID-19, there are case reports describing associated neuropsychiatric manifestations following COVID-19 vaccination, but none reported post heterologous bivalent boosting yet. This report centers on an immunocompetent man in his 40s who developed manic and psychotic symptoms temporally after receiving his first Moderna/Spikevax bivalent COVID-19 vaccine, with a lack of other contributing biological and psychological factors. He previously received three doses of the Pfizer-BioNTech/Comirnaty vaccine with no significant side effects. The manic and psychotic symptoms included elevated mood, increased irritability, psychomotor agitation, increased energy, decreased need for sleep, increased distractibility, grandiosity, and paranoid delusions. Following the development of these symptoms, he was hospitalized and treated with Olanzapine, after which his symptoms resolved. He recovered well, with no relapse of symptoms after discontinuation of Olanzapine and after discharge from the hospital. While vaccination is generally considered safe, a small minority of individuals may experience significant psychiatric adverse reactions following COVID-19 booster vaccination, perhaps a higher immunogenic risk if one received heterologous bivalent boosting, a suspicion raised in this case report.  This warrants further systematic study as COVID-19 evolves from being a pandemic to an endemic infection internationally.