COVID-19 Booster Vaccine Linked to CAD Onset, Chronic Symptoms

Reactions appeared in woman, 51 seven days after third vaccine dose

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A woman developed cold agglutinin disease (CAD), with high levels of cold agglutinins sustained for four months after symptom onset following a third dose of a vaccine for SARS-CoV-2, the virus that causes COVID-19, a case report from Japan.

According to its authors, “the present case indicates that the disease can become chronic, and provides insights into the pathogenesis [disease mechanisms] and treatment strategies.”

The report, “Chronic cold agglutinin disease after a third COVID-19 mRNA vaccination,” was published in the International Journal of Hematology.

Autoimmune hemolytic anemia (AIHA) is an umbrella term for a group of rare disorders wherein self-reactive antibodies are produced that target and destroy red blood cells. In the case of CAD, these autoantibodies are called cold agglutinins and lead to the destruction of red blood cells at low temperatures. 

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An increasing body of evidence suggests infection by SARS-CoV-2 may also trigger AIHA. In rare cases, a vaccination has also been pointed out as the trigger for it.

Researchers in Japan described the case of a woman diagnosed with CAD after receiving the third dose of BNT16B2b2, Pfizer-BioNTech’s mRNA vaccine against SARS-CoV-2.

The 51-year-old woman was seen at her primary clinic with severe generalized pain, finger joint pain, fatigue, and dark urine. These symptoms appeared seven days after she received a third dose of the COVID-19 vaccine from Pfizer-BioNTech. The two previous vaccines, both from Moderna, had been administered six months earlier. At the time, she had mild fever and headache.

Her medical history included migraine and gallstones, but no illness in the prior six months. She was being medicated with zolmitriptan (sold under the brand name Zomig, among others) and lomerizine hydrochloride for her migraines.

Her main complaint was finger joint pain, which led her primary care physician to suspect rheumatoid arthritis. Blood work showed she had anemia and abnormal blood clotting, but tests looking for antibodies associated with rheumatoid arthritis came back negative. She was diagnosed with a prolonged adverse reaction and was prescribed analgesics. Her symptoms persisted.

After four months of symptoms, she went to an outpatient clinic that specialized in blood-related disorders to try to pinpoint the causes of her anemia.

Lab tests showed alterations in her hemoglobin levels and confirmed immature red blood cells (reticulocytes) were present, as well as abnormally low levels of haptoglobin — all common signs of CAD. Hemoglobin is the protein in red blood cells that’s responsible for oxygen transport, while haptoglobin is a protein that binds and helps eliminate free hemoglobin.

A Coombs test was done to look for cold agglutinin antibodies, which were found at high levels. Additional lab work also was in line with a CAD diagnosis.

Extensive work to find a potential cause for CAD, including testing for several viral infections, bone marrow problems, and potential masses in certain organs, all came back normal. At the time of publication, she still showed signs of agglutination, or red blood cell clumping. She remains under careful follow-up without treatment.