COVID-19 Suspected Cause of Girl’s ANCA-associated Vasculitis

Mild virus in 16-year-old followed by symptoms and tests 'consistent with GPA'

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

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A 16-year-old girl developed granulomatosis with polyangiitis (GPA), a type of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), after being infected with SARS-COV-2, the virus that causes COVID-19, according to a recent case report.

Hers is the fourth known case of pediatric-onset AAV following COVID-19 infection, suggesting the virus could be a “precipitating trigger of autoimmunity and autoimmune disease” in children, the scientists wrote.

The case also “highlights the importance of considering AAV in a child following a recent COVID-19 infection because timely treatment may improve clinical outcomes,” the scientists wrote.

Their report, “A case of ANCA-associated vasculitis in a 16-year-old female following SARS-COV-2 infection and a systematic review of the literature,” was published in the journal Pediatric Rheumatology.

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AAV is a group of diseases marked by inflammation and damage to small blood vessels. The various types of AAV are categorized according to the tissues and organs where damage has occurred.

In patients with GPA, like this U.S. teenager, inflammation occurs in the walls of medium-sized and small blood vessels, a condition known as systemic necrotizing vasculitis. Inflammation takes place in a number of tissues and organs, but the kidneys and upper respiratory tract (nose, trachea, and ears) are usually the most affected in GPA. Most of these patients also develop autoantibodies that target the protein proteinase 3, called PR3-ANCAs.

Viral infections and pediatric-onset AAV

SARS-CoV-2 appears to initiate autoimmunity in both children and adults, the researchers noted. Although acute COVID-19 infection rarely causes severe symptoms in children, “a small percentage of children subsequently develop immune-mediated disease after COVID-19 infection,” they wrote, adding that some previous studies also reported an association between viral infections and pediatric-onset AAV, including GPA.

Researchers in Rhode Island detailed the case of a girl, with a history of asthma, who developed GPA after recovering from a mild case of COVID-19.

About one week after her recovery, she developed a persistent and non-productive cough. Due to her asthma, she was initially treated with albuterol, a bronchodilator or medication that works to relax and open up the airways. The treatment helped her wheezing but did not resolve her cough.

No changes were observed in a chest X-ray, but over the next month, she started having sinus pain and ear problems. She started treatment with antibiotics — azithromycin, cefdinir, and doxycycline — but her symptoms continued. The patient then was put on prednisone — a corticosteroid medication that reduces inflammation — for five days.

Doctors initially suspected chronic bilateral serous otitis media, a condition characterized by an ear infection with the presence of fluid in the middle ear. The girl underwent ear tube insertion, a surgery to place a tiny tube into the tympanum to drain fluid from the middle ear.

Her symptoms eased with this surgery, but she experienced hearing loss in both ears. A CT scan confirmed she had chronic inflammation in the middle ear.

Six weeks after these symptoms started, she was still wheezing, experiencing tightness in her chest and difficulty breathing, suggesting her asthma was worsening. Accordingly, she was given prednisone for five more days, along with albuterol, inhaled corticosteroids, and other long-term medications to control asthma.

Her symptoms eased again, but returned after she stopped the corticosteroids. Her response to the medications also declined over time.

A pulmonary function test three months later showed a moderate obstruction in the small airways. New chest X-rays and CT scans also found significant changes in the lungs that were consistent with bacterial infections, but lab tests were negative. Additional blood tests came back positive for PR3-ANCAs.

Evidence of granulomatous inflammation or vasculitis may be missing

“Our patient’s clinical presentation and positive serology is most consistent with GPA,” the researchers wrote.

Doctors then started rituximab, which works to lower the levels of antibody-producing immune B-cells, to treat her AAV, which she tolerated well, and tapered her off glucocorticoids.  She was given mycophenolate mofetil (brand name, CellCept) as a maintenance therapy.

A “marked improvement” in her symptoms was evident at her latest follow-up, with significant improvements in imaging studies and pulmonary function tests, the scientists reported. But screening for PR3 and ANCA antibodies remains negative to date, and continuing hearing loss has required her to use hearing aids.

Overall, these findings suggest that SARS-COV2 may be a virus capable of triggering AAV in children and adults.

According to the team, the development of autoantibodies, including ANCAs, after COVID-19 can be explained by the wide infiltration of immune cells at sites of tissue death, as well as the interaction between innate immunity and clotting after infection “that could contribute to tissue tolerance failure with antibody production.”

No evidence of granulomatous inflammation or vasculitis, however, is found in most lung tissue biopsies.

“Studies in adults with AAV have found that less than half of all biopsies show the characteristic inflammatory and vasculitic changes to confirm the diagnosis and sampling difficulty is often a limitation, which could have explained our patient’s biopsy findings,” the scientists wrote.

The team stressed that “more research is needed to better understand how SARS-CoV-2 may act as a precipitating trigger of autoimmunity and autoimmune disease in children.”