Italian physicians have suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can act as a trigger for new-onset autoimmune hemolytic anemia (AIHA), including cold agglutinin disease (CAD), according to a letter to the editor published in Pediatric Blood & Cancer.

The physicians described 2 case studies relating to CAD and coronavirus disease 2019 (COVID-19). The first was a 15-year-old boy who presented with nausea and vomiting, as well as asthenia. Initial examinations found him to be tachypneic, tachycardic, and febrile. Further investigations revealed the following: 

  • Severe hemolytic anemia (hemoglobin 3.7 g/dL, hematocrit 7.4%, bilirubin 3.51 mg/dL, lactate dehydrogenase [LDH] 425 U/L)
  • Positive direct antiglobulin test (DAT) with high title cold agglutinins (IgG+/C3d+)
  • Thrombocytopenia (platelets 77×109/L) with antiplatelet antibodies
  • Nasopharyngeal swab revealed the patient to be positive for SARS-CoV-2
  • Peripheral blood smear demonstrated severe anisocytosis and aggregates of red blood cells.

The patient was diagnosed with Evans syndrome (AIHA combined with thrombocytopenia) and transfused with red blood cell concentrates and intravenous (IV) corticosteroids. Only a partial response was recorded, so the patient received a 3-day regime of IV immunoglobulins on day 7. Hemoglobin levels improved rapidly and the patient was discharged on day 16.

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In the second case, a 2-year-old boy with beta thalassemia major received an allogeneic hematopoietic stem cell transplantation (HSCT) at 16 months of age from a matched unrelated donor. He then developed steroid-sensitive chronic graft-vs-host disease (GvHD). Three months later, bone marrow aspirate demonstrated complete donor chimerism. Six months postoperatively, he presented with pyrexia, anorexia, and weakness. A nasopharyngeal swab showed that he was positive for SARS-CoV-2. 

Upon admission, he was administered cyclosporine as GvHD prophylaxis. Blood tests revealed the following: 

  • Severe hemolytic anemia (hemoglobin 2.3 g/dL, hematocrit 4.8%, bilirubin 2.94 mg/dL, LDH 510 UI/L)
  • Positive DAT for cold pan-agglutinins (IgA+/IgG+/IgM+/C3c+/C3d+)
  • Severe anisocytosis and aggregates of red blood cells revealed by peripheral blood smear.

The patient was rapidly administered red blood cell concentrates and corticosteroids. His hemoglobin levels normalized slowly, and he required repeated transfusions, with the last on day 23. 

AIHA, including CAD, is rarely observed in children. It usually occurs secondary to viral or bacterial infections. In both case studies, the patients were administered corticosteroids as first-line therapy. SARS-CoV-2 infection could have resulted in immunological and inflammatory activation that made these children vulnerable to AIHA. Hence, the authors of the study recommended that “children with an underlying immune dysregulation may require particular attention considering a specific susceptibility to autoimmune manifestations during infections.” 


Zama D, Pancaldi L, Baccelli F, et al. Autoimmune hemolytic anemia in children with COVID-19. Pediatr Blood Cancer. Published online September 7, 2021. doi:10.1002/pbc.29330