SARS-CoV-2 virus may induce severe AIHA in young children

A case study reports that a healthy 2-year-old girl developed severe mixed autoimmune hemolytic anemia (AIHA) due to infection with SARS-CoV-2, the virus that causes COVID-19.

While reports of AIHA, a group of rare autoimmune diseases that include cold agglutinin diseases (CAD), secondary to COVID-19 are rare, “the rapid progression of the disease in our patient, a previously healthy individual, and severity is an extremely rare phenomenon, warning future providers about rapid decompensation,” the researchers wrote.

“Our case suggests that SARS-CoV-2 itself may be able to induce severe AIHA even in patients without underlying susceptibility, which has not been well documented in the literature,” the researchers wrote. They added, ” It is important to recognize AIHA quickly and start treatment as soon as possible.”

Case Report,”Rapidly progressive autoimmune hemolytic anemia in a pediatric patient with COVID-19,” published in the magazine Culeus.

AIHA is a rare disease characterized by the production of autoreactive antibodies that bind to red blood cells, causing their destruction, a process called hemolysis.

It can be classified as CAD, warm AIHA, and mixed AIHA, depending on whether the antibodies bind to red blood cells more readily at lower temperatures, higher temperatures, or both.

AIHA may occur secondary to infections, cancer, and other autoimmune diseases. “Although rare, SARS-CoV-2 infection has now been established as a secondary cause of AIHA based on cases reported in the literature,” which primarily included adults, the researchers wrote.

Most of these COVID-19-related cases also occur in patients with other co-morbidities, and there are rare cases of severe AIHA involving patients with normal immune systems.

Details of rare case in young child

Now, researchers at the University of Kansas School of Medicine describe a rare case of severe AIHA secondary to SARS-CoV-2 infection in an otherwise healthy 23-month-old girl.

For two days, she had worsening fatigue, sleepiness, and pain (unusually pale skin), along with fever and mild upper respiratory symptoms. Her parents took her to the emergency room because of her poor appearance.

Her vital signs were basically normal and she had no fever, but she was pale, unhealthy, sluggish, and had little reaction to painful stimuli. Further physical examination revealed that his eyes were pale, his breathing was rapid and shallow, and there were signs of muscle tone and poor circulation.

Her blood sugar levels were extremely low, so she received an intramuscular injection of glucagon (a hormone that raises blood sugar).

More lab work showed abnormalities, including high levels of certain immune cells, abnormal red blood cells, and extremely low levels of hemoglobin, the protein in red blood cells that carries oxygen throughout the body.

Imaging tests of the brain, chest and abdomen found no abnormalities and no signs of cancer cells or infection in the blood or urine. She tested negative for HIV and hepatitis A, B, and C, but tested positive for SARS-CoV-2, confirming the diagnosis of COVID-19.

Meanwhile, she was transferred to the pediatric intensive care unit and intubated.

Coombs test positive

The direct Coombs test, which evaluates whether antibodies and/or complement proteins are attached to the patient’s red blood cells, is positive for IgG and, to a lesser extent, complement component 3.

Given that in AIHA, IgG is the antibody type associated with high-temperature hemolysis and the immune complement system contributes to CAD-related hemolysis, the results suggest that “cold AIHA is dominated by warm components and to a lesser extent,” the team wrote. The girl also had low levels of CAD-specific antibodies called cold agglutinins.

After diagnosis of mixed AIHA, the girl received immunosuppressive therapy methylprednisolone, intravenous immune globulin (IVIG), and blood transfusions. IVIG provides specific healthy antibodies to neutralize autoreactive antibodies.

However, due to ongoing hemolysis, her heart’s pumping function was compromised, and once IVIG was started, she went into cardiac arrest. She was resuscitated with CPR and epinephrine, a vasopressor used to constrict blood vessels and raise blood pressure to reestablish blood flow.

The IVIG was discontinued and the transfusion completed, and her hemoglobin level increased. Despite continued vasopressor administration, her cardiac function remained unstable and she experienced two cardiac arrests.

Due to severe metabolic acidosis (too much acid in body fluids) and kidney failure, she received renal replacement therapy to help remove waste products from her blood.

Girl received 11 blood transfusions

On her second day in the hospital, she underwent plasmapheresis, a blood purification procedure, and then was treated with rituximab, which works by killing immune B cells that produce antibodies. She received a total of 11 blood transfusions.

“Her clinical parameters improved significantly between the third and fifth hospital days… and she discontinued vasopressors on the fifth hospital day,” the researchers wrote.

However, neurological examination results were abnormal, and she remained comatose and unresponsive during admission. Since red blood cell/hemoglobin levels are severely reduced and there is a lack of oxygen in the brain, this increases the likelihood of severe neurological damage.

Two brain tests 12 hours apart showed brain death and the girl was pronounced dead.

“This case illustrates the rapid and fatal sequelae (consequences) of autoimmune hemolytic anemia (AIHA) caused by COVID-19,” the researchers wrote, highlighting “the need for AIHA secondary to COVID-19 disease.” The importance of thorough inspection and management”.