Atypical hemolytic uremic syndrome triggered by mRNA vaccination against SARS-CoV-2: Case report

Abstract

Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries. In about 60% of cases, the genetic origin of the disease can be identified—commonly mutations affecting complementary factor H and MCP protein. Eculizumab, a monoclonal antibody to the C5 component of the complement, represents the current effective treatment.We describe a case of a young woman with a previous history of polyvalent allergies, who developed atypical hemolytic uremic syndrome after vaccination with mRNA vaccine against SARS-CoV-2. The disease manifested by scleral bleeding, acute renal insufficiency, anemia, and thrombocytopenia. The patient was treated with plasma exchanges without sufficient effect; remission occurred only after starting treatment with eculizumab. Genetic examination showed that the patient is a carrier of multiple inherited risk factors (a rare pathogenic variant in CFH, MCPggaac haplotype of the CD46 gene, and the risk haplotype CFH H3). The patient is currently in hematological remission with persistent mild renal insufficiency, continuing treatment with eculizumab/ravulizumab. By this case report, we meant to point out the need for careful monitoring of people after vaccination, as it may trigger immune-mediated diseases, especially in those with predisposing factors.

COVID-19 vaccination and Atypical hemolytic uremic syndrome

“…In one patient with dubious aHUS relapse, we cannot exclude that aHUS episode could have been diagnosed more profoundly and earlier if TMA parameters were assessed at the time of the start of symptoms. Our data confirms the findings of three adult cases with a pathogenic complement variant, who developed aHUS 1-6 days after BNT162b2, ChAdOx1 nCoV, or mRNA-1273 vaccination (19)(20)(21). In addition, two cases of, respectively, a Caucasian and African adult patient who developed TMA onset 5 and 10 days after ChAdOx1 nCoV vaccination have been reported (25, 26).…”

“…This underlines the importance of clear patient instruction and routine (laboratory) monitoring after COVID-19 vaccination for kidney function, proteinuria, TMA parameters, and blood pressure days after COVID-19 vaccination. Of note, since the complement system is capricious, uncomplicated previous (COVID- 19) vaccinations are no guarantee for future (non-)development of aHUS after vaccination. As the risk of aHUS recurrence after COVID-19 vaccination appears to be acceptable, we advise continuation of COVID-19 vaccination in aHUS patients, as this evidently reduces the risk of severe COVID-19 infection.…”

“…From January 2021 to May 2022 we prospectively identified Dutch pediatric and adult patients who developed onset or relapse aHUS after COVID-19 vaccination with the mRNA-based Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccine, and adenoviral-based AstraZeneca (ChAdOx1 nCoV- 19) or Janssen (Ad26.COV2.S) vaccine. Diagnosis of aHUS was made by the treating physician, yet consultation with the aHUS working group was a prerequisite for inclusion in this study.…”

“…Recently, vaccination campaigns against the coronavirus disease 2019 (COVID- 19), also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been implemented worldwide (11). Although rare, COVID-19 vaccination has been associated with severe thrombosis and thrombocytopeniaassociated complications (12)(13)(14).…”

“…In addition, a second or third COVID-19 vaccination has been statistically significant associated with (non-aHUS) glomerular disease relapse (15). Sporadically, patients developed complement-mediated HUS after COVID-19 infection and, even more rare, COVID-19 vaccination (14,(16)(17)(18)(19)(20)(21). Yet to date it is unknown to what degree vaccination against COVID-19 could trigger aHUS in pediatric and adult patients with a pathogenic complement variant.…”