Coronavirus Disease 2019 and Cold Agglutinin Syndrome: An Interesting Case

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. While patients with COVID-19 most frequently present with pneumonia, respiratory failure and acute respiratory distress syndrome, increasing cases of immune-mediated disorders such as autoimmune thrombocytopenia, haemolytic anaemia and antiphospholipid syndrome have been reported. In this article we describe a rare case of cold agglutinin syndrome (CAS) in a patient with COVID-19. The patient was a 77-year-old man with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency who presented with COVID-19 infection and acute respiratory failure. Initially he was started on intravenous steroids, antibiotics and hydroxychloroquine. Laboratory analysis revealed haemolytic anaemia with a positive direct anti-globulin test (DAT) and high titres of cold agglutinins. Hydroxychloroquine was stopped due to suspicion of haemolysis due to G6PD deficiency but the haemolysis persisted. Unfortunately, the respiratory failure progressed and the patient died. In summary, this article describes a rare case of CAS associated with COVID-19. CAS is a heterogenous group of cold autoimmune haemolytic anaemias occurring secondary to infections or malignancies. No definite treatment for CAS in COVID-19 patients has been approved so far. LEARNING POINTS Autoimmune haemolytic anaemia has been reported in COVID-19 patients. Cold agglutinin syndrome (CAS) can occur in patients with COVID-19. Efforts to determine the optimal management of CAS in COVID-19 patients must continue. Keywords: Coronavirus disease 2019, cold agglutinin syndrome, case report, autoimmune hemolytic anemia INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel enveloped RNA betacoronavirus that emerged in December 2019 in Wuhan, China and rapidly spread worldwide [1]. This virus is responsible for causing a multi-system disorder called coronavirus disease 2019 (COVID-19) syndrome. It has now been established that the hyperinflammatory response induced by SARS-CoV-2 causing fulminant and fatal cytokine release is a major cause of disease severity and death in infected patients [2,3]. While hypercoagulability [4], autoimmune cytopenias[5] and anti-phospholipid antibody syndrome[4] have emerged as the most common haematological disorders in COVID-19 patients, 14 cases of autoimmune haemolytic anaemiahave also been reported [6–12]. Individuals with autoimmune haemolytic anaemiaproduce warm, coldor mixed-reactive antibodiesthat are directed against antigens on the surface of red blood cells (RBCs) [13].Cold antibody autoimmune haemolytic anaemias can be further divided into cold agglutinin disease (CAD), which is primarily a low-grade clonal lymphoproliferative disorder, and cold agglutinin syndrome (CAS), which is a rare heterogenous group of cold immune haemolytic anaemias that occur secondary to infection or malignancy [14]. Here, we report a case of acute CAS associated with SARS-CoV-2.