PB0362 - Atypical Hemolytic Uremic Syndrome after SARS-CoV2 infection with C3 p.I1157T mutation

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare and lethal disease resulting in systemic thrombotic microangiopathies (TMA) due to complement dysregulation. Immune activation by viral infections and vaccination may trigger hemolytic attack. In fact, there have already been several reports of aHUS following SARS-CoV-2 infection or mRNA vaccination against SARS-CoV-2.

Aims: We have previously reported many cases with the C3 p.V1157T mutation. Some of these patients was infected with SARS-CoV-2 and developed TMA. We have also experienced patients with newly detected C3 p.V1157T mutation who developed TMA. Our experience will be useful in the treatment of patients who develop TMA after SARS-CoV-2 infection.

Methods: The clinical course of five patients with atypical hemolytic uremic syndrome with C3 p.I1157T mutation who were infected with SARS-CoV-2 after 2020 was reviewed.

Results: Two patients with a history of TMA and confirmed C3 p.V1157T mutation relapsed after infection with SARS-CoV-2. Two patients who developed TMA for the first time were newly diagnosed with C3 p.V1157T mutation, and all of them were treated with C5 inhibitors during the acute phase of TMA and recovered. One patient on C5 inhibitor maintenance therapy did not develop TMA after SARS-CoV-2 infection.

Conclusion(s): Patients with aHUS suffer from complement alternative pathway dysregulation due to genetic or autoimmune abnormalities. On the other hand, SARS-CoV-2 infection induces activation of the complement system, and complement activation is more pronounced in severe cases. This complement activation has been reported to be a major driver of thrombosis, a hallmark of severe COVID-19 patients. In other words, this suggests that SARS-CoV-2 infection is a major risk in patients with abnormalities of the complement regulatory system. Therefore, when patients with abnormalities of the complement regulatory system are infected with SARS-CoV-2, C5 inhibitors should be administered promptly.