Transient Cold Agglutinins in a Patient With COVID-19

Coronavirus disease 2019 (COVID-19) infection has been associated with various complications such as acute respiratory distress syndrome, acute kidney failure, myocardial infection, and thromboembolism. Cold agglutinin syndrome (CAS) has been associated with other viral infections such as Epstein-Barr virus (EBV), but there have been only a few reports of cold agglutination associated with COVID-19. In this report, we describe a case of transient cold agglutinin elevation in a COVID-19-infected patient. A 61-year-old man with hypertension, diabetes mellitus, and end-stage renal disease (ESRD) presented with shortness of breath, cough, and lethargy for five days. A clinical diagnosis of COVID-19 infection was made. The COVID-19 RNA qualitative real-time polymerase-chain-reaction (PCR) assay tested positive. During the hospital stay, he had progressive dyspnea requiring intubation and mechanical ventilation. During the third week of hospital stay, an acute drop in the hemoglobin (Hb) level to 4.5 g/dl (baseline Hb: 9 g/dl) was observed. The workup for acute anemia revealed a positive result for cold agglutinins, direct antibody test (C3d), and agglutination of the red blood cells were apparent on the peripheral blood smear. Further, cold agglutinin titers peaked during the third week of the onset of illness and significantly declined during the fifth week. These observational findings indicate that cold agglutinin titers might correlate with the disease activity.