Atypical Hemolytic Uremic Syndrome Occurring After Receipt of mRNA-1273 COVID-19 Vaccine Booster: A Case Report

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a dysregulation of the alternative complement pathway. Here, we report a previously healthy 38-year-old woman in whom aHUS developed after a COVID-19 vaccine booster. One day after receipt of a booster dose of mRNA-1273 vaccine, she felt ill. Because of persistent headache, nausea, and general malaise, she went to her general practitioner, who referred her to the hospital after detecting hypertension and acute kidney injury. A diagnosis of TMA was made. Her treatment consisted of blood pressure control, hemodialysis, plasma exchange, and respiratory support. Kidney biopsy confirmed the diagnosis of acute TMA. The patient was referred for treatment with eculizumab, and kidney function improved after initiation of this therapy. Genetic analysis revealed a pathogenic C3 variant. SARS-CoV-2 infection as a trigger for complement activation and development of aHUS has been described previously. In addition, there is one reported case of aHUS occurring after receipt of the adenovirus-based COVID-19 vaccine ChAdOx1 nCoV-19, but, to our knowledge, this is the first case of aHUS occurring after a booster dose of an mRNA COVID-19 vaccine in a patient with an underlying pathogenic variant in complement C3. Given the time frame, we hypothesize that the vaccine probably was the trigger for development of aHUS in this patient.

Keywords: Atypical hemolytic uremic syndrome (aHUS); Moderna; Spikevax; acute kidney injury (AKI); adverse event; case report; complement; coronavirus disease 2019 (COVID-19); eculizumab; kidney biopsy; mRNA vaccine; mRNA-1273; thrombotic microangiopathy (TMA).

Figure 1

Thrombotic microangiopathy findings in kidney biopsy specimens. (A) Light microscopy shows fibrin thrombi present in glomeruli and arterioles (white arrows), “tram-track” appearance of glomerular capillary wall (yellow arrows), and presence of severe acute tubular injury (silver stain; original magnification, ×200). (B) Ultrastructural examination by electron microscopy shows severe foot-process effacement (red arrow), ischemic wrinkling of glomerular capillary wall (red arrowhead), and endothelial cell swelling with loss of endothelial fenestrations (yellow arrow; original magnification, ×1,100).