ABSTRACT
BACKGROUND: Cold agglutinin syndrome (CAS) is associated with various diseases. Several studies of CAS associated with coronavirus disease 2019 (COVID-19) reported hemolytic anemia and thrombosis; however, the clinical significance of cold agglutinins (CA) in patients with COVID-19 is unclear. Here, we present two cases of CA identified in the context of COVID-19 without hemolytic anemia and clotting. CASE REPORT AND DISCUSSION: Two patients with no known risk factors for CA were diagnosed with COVID-19; peripheral blood smears reveal red blood cells (RBCs) agglutination. These patients showed a high CA titer. We confirmed retrospectively that the CA was an anti-I antibody. The two COVID-19 cases with a high CA titer showed no hemolysis or thrombosis. Mycoplasma pneumoniae is known to cause CAS, but not all patients who have a high CA titer show hemolysis. Coagulation abnormalities are documented in severe COVID-19 cases. Although CA increases the risk of thrombosis in those with lymphoproliferative diseases, the role of anti-I antibodies in COVID-19 is unclear. The impact of CAS on clinical presentations in COVID-19 remains a matter of verification. CONCLUSIONS: A high CA titer was identified in COVID-19 patients without hemolytic anemia and clotting. Anti-I antibodies were identified. Further studies are required to clarify the pathophysiology of CA in COVID-19.