Researchers from Malaysia reported the case of a woman who developed cold agglutinin disease (CAD) following a COVID-19 infection. “We believe that her condition deteriorated due to the ‘cytokine storm’ and complement cascade,” they wrote in an article published in the Hong Kong Medical Journal.

The link between autoimmune hemolytic anemia such as CAD and COVID-19 has not been well studied and the pathophysiology of this association is not well understood. However, a number of complications related to COVID-19 especially involving hematology are increasingly being reported.

The case reported here is a woman, aged 70 years who had diabetes mellitus, hypertension, and dyslipidemia. She presented to the hospital after 3 days of fever, cough, and runny nose. She was diagnosed with COVID-19 following a polymerase chain reaction test.

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Hematological analysis showed that her hemoglobin level was 8.1 g/dL and there was marked red blood cell agglutination, which dispersed when the blood was heated to 37 °C, indicating CAD. A direct antiglobulin test revealed the presence of anti-complement antibodies.

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The researchers reported that 7 days later the patient developed hypoxaemic respiratory failure and she needed oxygen supplementation. She was also given intravenous methylprednisolone as a treatment for severe COVID-19 pneumonia, to which she responded well. She was then prescribed a tapering dose of dexamethasone and had a blood transfusion. 

The patient was discharged from the hospital 21 days later and the researchers reported that she was transfusion-independent for 1 week. “At 1-month follow-up examination, the patient remained well,” they said.

The researchers concluded that the prompt administration of methylprednisolone could reduce mortality and dependence on a ventilator.

CAD is a rare type of autoimmune hemolytic anemia in which exposure to temperatures between 3 °C and 5 °C or (37 °F and 41 °F) leads to an immune system attack against erythrocytes causing lysis.


Chang CY, Chin HH, Chin PW, Zaid M. Cold agglutinin-mediated autoimmune haemolytic anaemia associated with COVID-19 infection: a case report. Hong Kong Med J. Published online April 27, 2022. doi:10.12809/hkmj219828