Potential link between COVID-19 infection/vaccination and the onsets of TAFRO syndrome and idiopathic multicentric castleman disease

COVID-19 infection and vaccination have been reported as potential triggers for various autoimmune diseases, including TAFRO syndrome and idiopathic multicentric Castleman disease (iMCD). We investigated the incidence of TAFRO syndrome and that of iMCD in the patients admitted to Nagasaki University Hospital over a 10-year period from November 2014 to October 2024. The primary endpoint was the incidences of TAFRO syndrome/iMCD before and after the COVID-19 pandemic. The secondary endpoint was the impact of COVID-19 vaccination ≤4 weeks of disease onset on the patients' prognoses. Our analyses revealed that in the 5 years and 5 month-period before the pandemic, there were seven cases of TAFRO syndrome/iMCD (1.3 cases/year), while in the 4 years and 7 month-period following the pandemic's onset, 18 cases were identified (3.9 cases/year). Specifically, for iMCD-TAFRO and TAFRO without iMCD, the incidence rose from two cases (0.4 cases/year) pre-pandemic to 11 cases (2.4 cases/year) post-pandemic, representing a marked increase. Among the 13 cases of iMCD-TAFRO and TAFRO without iMCD observed, four patients developed symptoms within 4 weeks of receiving the COVID-19 vaccine, and all required ICU admission. Conversely, among the nine patients without a recent vaccination history, only two required ICU care (p = 0.02). Although potential confounders which could influence the diagnosis (e.g., increased awareness of the disease) were not controlled for, our findings suggest a possible link between COVID-19 infection or vaccination and the onsets of TAFRO syndrome and iMCD. COVID-19 vaccination is a crucial public health strategy to reduce COVID-19-related death and disability, but TAFRO syndrome that develops post-vaccination may progress to severe illness requiring ICU care, highlighting the need for careful monitoring.