2 Cases of CAD in France Linked to COVID-19, Report Suggests

Coronavirus disease 2019 (COVID-19) could cause cold agglutinin disease (CAD), a case report of two patients from France suggests.

The cases were described in a letter to the editor of the journal Annals of Hematology. The letter, submitted by researchers from the University of Paris, was titled“SARS-CoV-2-associated cold agglutinin disease: a report of two cases.”

The first of the two cases involved a 43-year-old woman with a medical history of obesity and untreated multiple sclerosis. The woman was hospitalized after a 10-day period with symptoms of weakness, fever, cough, diarrhea, and shortness of breath (dyspnea). At admission, her levels of hemoglobin — the protein that carries oxygen in red blood cells — were normal (13.1 g/dL).

A molecular test confirmed that she was positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the agent causing COVID-19.

A CT scan of the chest showed signs of severe interstitial pneumonia, in which the air sacs of the lungs become inflamed. The patient received oxygen support and a combination of antibiotics (ceftriaxone and azithromycin for three days, then tazocillin for another three days), which rapidly improved respiratory function.

At day six, her levels of hemoglobin dropped to 6.1 g/dL, and she showed signs of red blood cell destruction (hemolysis), including elevated levels of bilirubin. Bilirubin, which passes through the liver and is eventually excreted from the body, is an orange-yellow substance made during the normal breakdown of red blood cells.

Additional laboratory testing showed that the patient also was positive for cold agglutinins — the autoantibodies found in people with the rare acquired autoimmune disorder CAD. She was given a blood transfusion, which ultimately led to increased hemoglobin levels and eased the destruction of her red blood cells.

The second patient to develop CAD was a 63-year-old man with a medical history of hypertension. He was admitted to the intensive care unit due to severe acute respiratory syndrome, a respiratory disorder caused by a SARS-associated coronavirus.

In the two weeks preceding his admission, the man had fever, cough, and shortness of breath that worsened with time. The molecular test revealed he was positive for SARS-CoV2.

An initial blood analysis showed the patient had a non-regenerative normocytic anemia, a blood problem. With this condition, the body fails to respond adequately to a drop in the number of red blood cells. Further blood tests confirmed the presence of cold agglutinins.

After six days in the hospital, the levels of hemoglobin decreased to 8.2 g/dL, but then increased within nine days along with clinical improvement.

“We here report two supplemental cases of SARS-CoV-2-associated autoimmune hemolytic anemia with cold agglutinins which seems to be a rare but nevertheless real complication of this condition,” the researchers wrote.

“We believe that a more extensive investigation of anemia in SARS-CoV2 patients … might be useful for the detection of other cases of CAD and appropriate management of anemia during SARS-CoV2-infection” that causes COVID-19, they concluded.