Case Report Highlights Possible CAD, COVID-19 Link

The case of a man with COVID-19 who temporarily developed elevated levels of cold agglutinins — the self-reactive antibodies that cause cold agglutinin disease (CAD) — was described in a recent report.

According to researchers, this is the third known case of elevated cold agglutinin levels documented in a COVID-19 patient. Together, these cases suggest the existence of a possible link between the two disorders, and highlight the need for further research to clarify this hypothesis.

Titled “Transient Cold Agglutinins in a Patient With COVID-19,” the case report study was published in the journal Cureus.

The patient described in this report was a 61-year-old man with a variety of pre-existing health conditions, including high blood pressure, diabetes, and kidney disease. The man went to the hospital after experiencing cough, fever, lethargy, and progressively worsening shortness of breath for five days. At the hospital, he tested positive for SARS-CoV-2, the virus that causes COVID-19.

The next day, the patient developed progressive respiratory failure, requiring intubation and mechanical ventilation. He was given a combination of medications aimed at treating the infection, including hydroxychloroquine, azithromycin, and methylprednisolone.

On his fifth day at the hospital, the patient developed anemia, or abnormally low levels of hemoglobin, the protein red blood cells use to transport oxygen throughout the body. Notably, he did not show any signs of active bleeding. But this development nonetheless prompted physicians to order additional laboratory tests.

These tests revealed that the man had abnormally high levels of cold agglutinins, the self-reactive antibodies that target and destroy red blood cells in people with CAD, through a process known as hemolysis.

Although this patient had high levels of cold agglutinins, “no evidence of hemolysis was established in this case,” the researchers wrote.

As such, the researchers said that this case did not constitute one of true CAD. Instead, they speculated that this patient’s anemia was likely related to complications from COVID-19.

The team said that the highly inflammatory conditions that are seen in COVID-19 can lead to hemolysis, though they noted that the disease-causing mechanisms of COVID-19 are not fully established.

The patient’s anemia was treated with blood transfusions. After about five weeks in the hospital, his condition improved, and his cold agglutinin levels decreased.

“The patient’s Hb [hemoglobin] levels stabilized and cold agglutinin [levels] were trending down with clinical improvement,” the researchers wrote.

According to the researchers, this case highlights the potential association between COVID-19 and cold agglutinins. They noted that other types of infections are known to cause CAD, in which the condition is called secondary CAD.

The team called for further research to better understand the connection between both conditions.

“SARS-CoV-2 infection should be considered as one of the causes behind the development of cold agglutination,” they concluded.