COVID-19 Linked in 3 Cases to Severe aHUS; All Treated With Soliris

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by Marta Figueiredo PhD |

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Some COVID-19 patients may develop severe atypical hemolytic uremic syndrome (aHUS), but it can be completely or partly resolved with Soliris (eculizumab), according to three cases reported in a recent study.

These cases add to a few other aHUS cases reported to be likely triggered by COVID-19, further emphasizing the possibility of this complication amid the ongoing global pandemic.

Data also suggests that Soliris and other anti-complement therapies may be beneficial for progressive COVID-19 with thrombotic microangiopathy (TMA) — the formation of blood clots in small blood vessels that can cause organ damage, most commonly in the kidneys. However, appropriate clinical trials are needed to further confirm this, the researchers said.

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The study, “Thrombotic Microangiopathy Triggered by COVID-19: Case Reports,” was published in the journal Nephron.

aHUS is a rare disease characterized by the progressive destruction of red blood cells, low platelet counts, and TMA. The condition is caused by the excessive activation of the alternative pathway of the complement system, a set of more than 30 blood proteins that form part of the body’s immune defenses.

Most aHUS patients carry disease-predisposing mutations in complement system genes, but the condition also can be triggered by uncontrolled complement activation in response to infections.

SARS-CoV-2, the virus that causes COVID-19, was previously shown to promote prolonged activation of the alternative complement pathway and to lead to blood vessel damage, thereby being a potential cause of TMA and aHUS in infected patients.

To date, a few cases of COVID-19 associated with severe TMA have been reported, and this complication is the main cause of kidney damage in COVID-19 patients.

Now, researchers in Russia described the cases of two women (ages 49 and 66) and one man (39 years old) who developed severe aHUS and kidney damage after being infected with SARS-CoV-2.

The man had a long history of high blood pressure (hypertension) and the older woman had a 10-year history of diabetes. No particular risk factor was identified in the younger female patient.

All experienced common signs of COVID-19, the most frequent being fever and respiratory symptoms. CT scans showed at least 50% of lung involvement, with both the man and the older woman showing signs of pneumonia, an infection that leads to inflammation of the air sacs in the lungs.

Lab tests done at the patients’ hospital admissions revealed reduced hemoglobin levels, indicative of red blood cell destruction, abnormally low platelet counts, and increased lactate dehydrogenase — a marker of tissue damage. The results also showed impaired kidney function that required hemodialysis in the younger woman and the man.

Other types of treatment included immunosuppressive therapy, anti-clotting medications, antibiotics, anti-viral medications, oxygen therapy, and plasma exchange — a procedure in which a patient’s plasma, or the liquid portion of blood, is removed and replaced.

The older woman developed acute respiratory distress syndrome, a life-threatening lung injury that allows fluid to leak into the lungs, and underwent invasive mechanical ventilation. Besides SARS-CoV-2, two bacterial species also were detected in her lungs.

Despite all treatment measures, the patient’s blood-related condition kept progressing with severely low platelet counts and the presence of red blood cell fragments, a feature of TMA.

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The 49-year-old woman was discharged, but two months after contracting COVID-19 her kidney function had not yet improved. Further testing confirmed abnormal activation of the alternative complement pathway and the presence of kidney damage in a biopsy.

Based on clinical symptoms and lab results, as well as the exclusion of other TMAs and autoimmune diseases, all three patients were diagnosed with aHUS, which was likely triggered by COVID-19.

Following diagnosis, treatment with Soliris, a complement-suppressing therapy, was started for all three patients, resulting in positive signs.

Six days after the first Soliris dose, the older woman died of a serious generalized infection caused by another bacterium.

After three weekly doses, the man refused further treatment, despite the fact that his kidney function was not yet normalized and, therefore, he continued to undergo hemodialysis. In the younger woman, four months of treatment with Soliris resulted in the normalization of most lab results, and she continued to receive the therapy.

“In the absence of other causes of TMA, we believe that aHUS is triggered by abnormal complement activation in COVID-19 patients,” the researchers wrote.

“It is not clear whether SARS-CoV-2 played a role in widespread [blood vessel] damage through direct complement activation,” they added, as it is possible that these patients carried aHUS-predisposing mutations. However, genetic testing was not performed in any of these patients.

Based on these cases, researchers also recommended that anti-complement therapies such as Soliris “be considered in [non-responsive] cases of progressive COVID-19” with TMA.

Still, “controlled clinical trials are required before a definitive statement can be made,” they concluded.