Douen and colleagues described a case study of a 77-year-old female with COVID-19-induced cold agglutinin disease (CAD) in an article published in the Chest journal.

COVID-19 is best described as a systemic disease, the authors said. It’s known to have significant effects in patients with hematological diseases. For example, research has shown that 1 of the many complications of COVID-19 is an increase in thrombotic events.

However, little is known of its effects on autoimmune hemolytic anemia, of which CAD is a subtype. CAD is known to be associated with viral infections, autoimmune diseases, and malignancy, but the number of COVID-19 associated CAD cases reported is vanishingly small.

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“So far 4 cases have been reported with COVID-19-induced CAD, and further monitoring and investigation are required,” the research team wrote. 

Read more about CAD etiology 

The researchers added to this body of data by describing a case of CAD induced by COVID-19. These were the salient points of the case report: 

  • A 77-year-old woman presented with cough, dyspnea, and hematuria. She had underlying hypertension, cardiac failure, and paroxysmal atrial fibrillation. 
  • Initial examination revealed that she had pyrexia (101.8℉) and tachypnea. Chest auscultation revealed decreased breath sounds in all lung areas except the bilateral upper lung fields. A chest X-ray was ordered, revealing patchy bilateral airspace and interstitial opacities with prominence of the interstitial vasculature.
  • The patient tested positive for COVID-19. 
  • Blood results revealed anemia with disproportionately low hematocrit and high mean corpuscular hemoglobin concentration. White blood cells, platelets, and total bilirubin levels were normal.
  • Peripheral blood smears revealed red blood cell agglutination. In addition, antibodies of cold agglutinin were detected. 
  • Direct antiglobulin test detected antibodies that complement component C-3 and were against IgG. Researchers also discovered that D-dimers, fibrinogen, lactate dehydrogenase, and haptoglobin were elevated. Antinuclear antibody titers were midly positive. 
  • The patient was negative for human immunodeficiency virus, hepatitis B surface antigen and antibody, hepatitis C antibody, antidouble stranded DNA, and mycoplasma immunoglobulin G/immunoglobulin M antibodies. 
  • After excluding possible causes, the patient was diagnosed with COVID-19-induced CAD. She received treatment for COVID-19, heart failure, and warmed blood transfusions for anemia.


Douen A, George T, Ramsamooj K, Basit A, Kaur P, Shah T. A cold case of Covid-19-induced cold agglutinin diseaseChest. Published online October 11, 2021. doi:10.1016/j.chest.2021.07.823