1st Case of CAD Due to COVID-19 in Asia Treated With Corticosteroids

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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An elderly woman in Japan is the first reported patient in Asia to develop cold agglutinin disease (CAD) due to COVID-19, according to a new case study.

The patient was found to have anemia, or an unusually low red blood cell count, that was not resolved with a blood transfusion. Her treatment thus involved the use of corticosteroids, which are usually not recommended for CAD secondary to an infection.

“Anemia persisted even after blood transfusion and COVID-19 recovery, with the re-administration of corticosteroids required,” the researchers wrote, noting the woman was discharged from the hospital after 18 days.

Her case was described in the report “Severe Anemia Due to Cold Agglutinin Syndrome in a COVID-19 Patient with IgM Monoclonal Gammopathy of Undetermined Significance Successfully Treated with Corticosteroids,” published in the journal Internal Medicine.

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CAD occurs when the body makes cold agglutinins, which are antibodies that attack and damage red blood cells at low temperatures. Sometimes, it occurs in association with an underlying illness, such as an infection, in which case it is called secondary CAD.

Earlier this year, a team of researchers in the U.S. reported the case of an elderly woman with a history of secondary CAD who experienced a worsening of her symptoms after contracting an infection with SARS-CoV-2, the virus that causes COVID-19.

Now, a team of researchers in Japan reported the case of a 72-year-old woman who also developed symptoms of CAD secondary to COVID-19.

The woman visited the hospital with a two-week history of cough and shortness of breath upon exertion. A blood test revealed she had anemia. She also had a history of high blood pressure.

A lab test came back positive for SARS-CoV-2. Yet, the amount of virus that could be detected was relatively low. Based on this finding, doctors estimated that COVID-19 had had its onset about two weeks prior to her hospital visit.

Additional blood tests revealed high levels of cold agglutinins, and a Coombs test also came back positive. Of note, the Coombs test is used to look for cold agglutinins or other antibodies that are bound to red blood cells.

The patient also had low levels of hemoglobin — a protein in red blood cells that is responsible for transporting oxygen — and haptoglobin, a liver-made protein that binds to hemoglobin. Conversely, she had high levels of lactate dehydrogenase (LDH) and bilirubin, two markers of red blood cell destruction.

Based on these findings, doctors diagnosed her with CAD.

Further blood testing revealed high levels of IgM, a protein that is made by certain immune cells in the bone marrow to help the body fight infection. An abnormal increase in the production of this type of protein is called a gammopathy, and the woman was diagnosed with a monoclonal gammopathy of undetermined significance (MGUS).

These findings pointed at COVID-19 and MGUS as the potential causes of CAD.

The woman received a red blood cell transfusion and was given oral dexamethasone, a corticosteroid, for 11 days. She also received the antiviral Veklury (remdesivir) to treat COVID-19. 

Her breathing improved and her anemia eased gradually, and treatment with dexamethasone was stopped because both COVID-19 and CAD were deemed to have resolved.

“We concluded that COVID-19 was the main cause of the patient’s CAS [secondary CAD] at that time point and that the CAS would improve spontaneously following the resolution of COVID-19,” the researchers wrote.

However, her hemoglobin levels dropped again after treatment with dexamethasone was stopped. She was started on oral prednisolone, another corticosteroid, and her hemoglobin levels rose.

The woman was discharged and advised to avoid cold environments. Treatment with prednisolone was tapered, and symptoms did not return.

“Although corticosteroids are not a standard therapy for CAS, they might be effective for CAS secondary to COVID-19 complicated with MGUS,” the researchers wrote.