SARS-CoV-2 virus may have induced toddler’s severe AIHA
Case report describes rare, fatal case of mixed autoimmune hemolytic anemia
A 2-year-old, healthy girl developed a severe, mixed form of autoimmune hemolytic anemia (AIHA) as a result of infection with SARS-CoV-2, the virus that causes COVID-19, a case study reports.
While AIHA — a group of rare autoimmune conditions that include cold agglutinin disease (CAD) — secondary to COVID-19 have been reported rarely, “the rapid progression and severity of our patient’s illness, a previously healthy individual, is an incredibly rare phenomenon and warns future providers about rapid decompensation,” the researchers wrote.
“Our case illustrates that SARS-CoV-2 may itself be capable of inducing severe AIHA even in patients with no underlying predisposition, which has not been well documented in the literature,” the researchers wrote. They added that it is “important to quickly identify AIHA and initiate therapy as quickly as possible.”
The case report, “Rapidly Progressing Autoimmune Hemolytic Anemia in a Pediatric Patient With COVID-19,” was published in the journal Cureus.
AIHA is a rare condition characterized by the production of self-reactive antibodies that bind to red blood cells, leading to their destruction, a process called hemolysis.
It can be classified as CAD, warm AIHA, and mixed AIHA, depending on whether the antibodies bind more easily to red blood cells at lower temperatures, higher temperatures, or both.
AIHA can 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 mainly included adults, the researchers wrote.
Most of these COVID-19-associated cases also have been reported in patients with other simultaneous conditions, with few concerning cases of severe AIHA in patients with normal immune systems.
Details of the toddler’s rare case
Now, researchers at the University of Kansas School of Medicine described the rare case of a previously healthy 23-month-old female toddler who developed severe AIHA secondary to SARS-CoV-2 infection.
She had experienced worsening fatigue, drowsiness, and pallor (unusually pale skin) for two days, along with fever and mild upper respiratory tract symptoms. Her parents took her to the ER due to her ill appearance.
Her vital signs were mostly normal and she had no fever, but she had an unhealthy pale look, was sluggish, and showed minimal response to painful stimuli. Further physical examination revealed eye pallor, quick and shallow breathing, and signs of poor muscular tone and blood circulation.
Her blood sugar levels were extremely low and she was given an intramuscular injection of glucagon, a hormone to raise blood sugar.
More lab work showed several abnormalities, including high levels of certain immune cells, abnormal red blood cells, and extremely low levels of hemoglobin, which is the protein in red blood cells that transports oxygen throughout the body.
Imaging tests in the brain, chest, and abdomen found no abnormalities, and there were no signs of cancer cells or of blood or urine infection. She tested negative for HIV and hepatitis A, B, and C, but tested positive for SARS-CoV-2, confirming a COVID-19 diagnosis.
In the meantime, she was transferred to the pediatric intensive care unit and intubated.
Coombs test was positive
A direct Coombs test, which assesses whether antibodies and/or complement proteins are attached to a patient’s red blood cells, was positive for the IgGs and to a minor extent to the complement component 3.
Given that in AIHA, IgGs are the type of antibody associated with hemolysis at warm temperatures, and the immune complement system contributes to CAD-related hemolysis, the results indicated “a predominantly warm and minor component of cold AIHA,” the team wrote. The girl also had low levels of CAD-specific antibodies, called cold agglutinins.
Upon the diagnosis of mixed AIHA, the girl received the immunosuppressive therapy methylprednisolone, intravenous immunoglobulins (IVIG), and blood transfusions. IVIG delivers specific healthy antibodies to neutralize self-reactive antibodies.
However, due to ongoing hemolysis, her heart’s pumping function was compromised and she went into cardiac arrest as soon as she began IVIG. She was resuscitated with CPR and epinephrine, a vasopressor used to constrict blood vessels and increase blood pressure to reestablish blood flow.
IVIG was stopped and blood transfusion completed, with an increase in her hemoglobin levels. Despite continuous administration of vasopressors, her heart function was unstable and she experienced two episodes of cardiac arrest.
Due to severe metabolic acidosis — when body fluids have too much acid — and kidney failure, she was placed on kidney replacement therapy that helped clean her blood from waste products.
Girl received 11 blood transfusions
On the second day of hospitalization, she underwent plasma exchange, a blood-cleaning procedure, followed by treatment with rituximab, which works by killing antibody-producing immune B-cells. In total, she received 11 blood transfusions.
“Between hospital days three to five, her clinical parameters improved significantly …, and she was weaned off vasopressors by hospital day five,” the researchers wrote.
However, neurological exams were abnormal, and she remained unresponsive and in a coma-like state for the duration of hospital admission. This raised the possibility of severe neurological damage due to severely low red blood cells/hemoglobin levels and not enough oxygen in the brain.
Two brain tests separated by 12 hours showed brain death, and the girl was declared dead.
“This case illustrates the rapid and fatal sequela [consequence] caused by autoimmune hemolytic anemia (AIHA) from COVID-19,” highlighting “the importance of thorough workup and management of AIHA secondary to COVID-19 illness,” the researchers wrote.