Pediatric Cold Agglutinin Syndrome in the Post-COVID19 Era

Purpose: This case series describes an increase in the incidence of cold agglutinin syndrome (CAS) in children in Singapore following relaxation of COVID-19-related non-pharmacological interventions (NPIs). Methods: Clinical data of patients diagnosed with CAS from November 2022 to October 2023 following the relaxation of NPIs in October 2022 were collected retrospectively. Data on the number of CAS cases diagnosed before the pandemic (2018-2019) and during the pandemic (January 2020-October 2022) were collected. Results: Thirteen patients were diagnosed with CAS from November 2022 to October 2023, as compared to zero cases diagnosed during the COVID-19 pandemic. There were also more cases than before the pandemic (one case in 2018 and three cases in 2019). The median age of the 13 patients was 4.6 years (range 1.8-12 years). The most commonly detected virus was rhinovirus/enterovirus (54%). Nine children required red cell transfusions. Five patients received corticosteroids. Conclusion: An increase in the number of pediatric CAS cases has been observed since the COVID-19 pandemic. This may be due to an overall increase in viral infections due to the immunity debt from COVID-19 related NPIs. Another possible explanation is the "hygienist theory, " which postulates a causal relationship between the decline in infections and increase in immunological disorders.