COVID-19 Triggers aHUS Relapses in 2 Brothers in Case Report

Early treatment with Soliris was effective in alleviating symptoms of aHUS relapse

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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COVID-19 was a strong trigger for relapses of atypical hemolytic uremic syndrome (aHUS) in two brothers who were genetically predisposed to the syndrome, a recent case study reports.

In both cases, treatment with Soliris (eculizumab) was effective in alleviating symptoms when given in the early stages of relapse.

The report, “Atypical Hemolytic Uremic Syndrome after SARS-CoV-2 Infection: Report of Two Cases,” was published in the International Journal of Environmental Research and Public Health.

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aHUS is a rare disease characterized by the formation of blood clots in small blood vessels, which can damage several organs, such as the kidneys. Its most common manifestations include hemolytic anemia, which occurs when red blood cells are destroyed faster than they are made, low platelet counts (or thrombocytopenia), and acute kidney failure.

The disease is caused by an overactivation of the complement cascade, a network of proteins that help defend the body against disease-causing microbes. Most patients diagnosed with aHUS carry genetic mutations in complement system genes, such as MCP, that increase their susceptibility to developing aHUS.

However, genetic mutations alone are usually insufficient to trigger aHUS on their own. In most cases, a triggering event is also necessary, such as a viral or a bacterial infection, to activate the immune system.

SARS-CoV-2, the virus that causes COVID-19, has been shown to cause damage to endothelial cells — those lining blood vessel walls. This damage leads to an inflammatory response, namely an uncontrolled activation of the complement system, that promotes the formation of blood clots.

In the report, researchers in Poland described the case of two brothers, ages 19 and 23, who experienced aHUS relapses after being infected with SARS-CoV2. Both brothers carried an heterozygous mutation in the MCP gene. Heterozygous means the mutation was present only in one of the two copies of the gene.

The younger brother was diagnosed with aHUS at age 14, and has experienced two relapses of mild intensity: one at age 14 and the other at 16. Both relapses were related to upper respiratory tract infections, for which he received treatment.

In October 2021, at 18, he was admitted to hospital for fever, cough, headaches, lower back pain, hematuria (blood in the urine), and oliguria, a condition in which there is a marked reduction in urine volume. A molecular test confirmed he was positive for SARS-CoV2.

Blood work showed the patient had thrombocytopenia, increased formation of blood clots, and signs of hemolytic anemia, including high bilirubin and low hemoglobin levels. In addition, inflammation markers (CRP, PCT, and IL-6) also were increased. A chest CT scan showed no lung involvement.

The patient was treated with an antibiotic (ceftriaxone), antiviral therapy (remdesivir), and fresh frozen plasma, which is meant to replace a person’s plasma — the non-cellular parts of blood.

However, during hospitalization, his anemia and thrombocytopenia worsened significantly and the patient was diagnosed with another aHUS relapse. He was transferred to the nephrology department, where he began treatment with Soliris, a complement inhibitor.

Despite experiencing secondary effects (stomach pain, nausea, and vomiting) and changes in his liver shape and function, the patient showed improvements in his platelet counts and creatinine levels seven days after his first dose of Soliris. Within two weeks, markers of kidney function were normalized. The patient was discharged from the hospital after his second dose of Soliris. After one month of treatment, his liver function normalized.

Complement activity was significantly reduced in the patient and within eight weeks of treatment, the shape of his liver also returned to normal.

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His older brother was diagnosed with aHUS at age 7, and experienced three relapses of mild intensity, at ages 7, 8, and 21. All had been linked to upper respiratory tract infections.

This patient was admitted to the emergency department due to fever, weakness, and hematuria. He also tested positive for SARS-CoV-2 with potential lung involvement, as confirmed by a chest X-ray.

Blood tests confirmed thrombocytopenia, increased formation of blood clots, and signs of hemolytic anemia. Creatinine levels also were elevated. Proteins were found in his urine (a condition called proteinuria), and he showed signs of liver damage and inflammation — specifically, increased levels of two liver enzymes, called aspartate aminotransferase and alanine transaminase. Levels of CRP, an inflammatory marker, were mildly increased.

The patient was diagnosed with another aHUS relapse and started on Soliris.

One week after the first dose, the patient’s platelet counts and liver and kidney function normalized, and he was discharged. His anemia and proteinuria resolved within two weeks.

Overall, these two cases show that with Soliris administered “at an early stage of disease relapse, renal dysfunction was completely restored, and the hematological [blood] parameters improved,” the researchers wrote.

“The duration of treatment with eculizumab in our patients will be considered individually, taking into account the potential risks and benefits of treatment,” they wrote.

The researchers recommended that patients with aHUS be made aware of potential relapse triggers and seek medical attention promptly to prevent disease progression.