Researchers reported a case of cold agglutinin disease (CAD) occurring secondary to severe SARS-CoV-2 infection that was treated with eculizumab and published their findings in BMJ Case Reports. They showed that the eculizumab therapy quasi-resolved the hemolysis, but ultimately the patient died of the COVID-19 infection.

“Secondary CAD can be related to hematological or infectious disease. Considering the delayed action of rituximab compared with eculizumab and the fact that steroids are not effective in CAD we chose to treat hemolysis with eculizumab,” the authors explained.

“Although our patient died as a result of his severe COVID-19 infection, we considered the CAD episode cured due to the absence of recurrence of hemolysis.”

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The authors suspect that the inflammatory and prothrombotic triggers in SARS-CoV-2 infection could be enhanced by complement pathway activation, leading to CAD and initiating hemolysis. Eculizumab, an anti-C5 antibody, inhibits hemolysis by blocking membrane attack complex formation, and it has been shown in 1 study to reduce mortality in patients in the intensive care unit with severe SARS-CoV-2 infection.

In this case, although rituximab was shown to be effective in a patient with CAD and nonlife-threatening COVID-19 infection, the 2-week delay inaction of the drug led the research team to select eculizumab instead. The day after the infusion of eculizumab, the patient’s biomarkers or hemolysis improved, and no recurrence occurred.

The authors note that targeted blockade with eculizumab is useful for treating hemolysis in CAD and could be of interest in future cases of CAD that are secondary to SARS-CoV-2 infection.


Dawudi Y, Federici L, Debus J, et al. Cold agglutinin disease secondary to severe SARS-CoV-2 treated with eculizumab. BMJ Case Reports. Published online May 2, 2022. doi:10.1136/bcr-2021-242937