Case series: coronavirus disease 2019 infection as a precipitant of atypical hemolytic uremic syndrome: two case reports

Abstract

Background Atypical hemolytic uremic syndrome is an exceedingly rare thrombotic microangiopathy caused by accelerated activation of the alternative complement pathway. Case presentation Here, we report two cases of patients presenting with suspected atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 infection. The first patient, a 25-year-old Hispanic male, had one prior episode of thrombotic microangiopathy presumed to be atypical hemolytic uremic syndrome precipitated by influenza A, and re-presented with thrombocytopenia, microangiopathic hemolytic anemia, nonoliguric renal failure, and normal ADAMTS13 activity, with confirmed coronavirus disease 2019 positivity. The second patient, a 31-year-old Caucasian female, had no personal history of thrombotic microangiopathy, though reported a family history of suspected atypical hemolytic uremic syndrome. She presented with similar laboratory derangements, oliguric renal failure requiring hemodialysis, and confirmed coronavirus disease 2019 positivity. Both patients were treated with eculizumab with complete resolution of their hematologic and renal complications. Conclusion To our knowledge, this represents the largest case series of atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 in adults.

COVID-19: A Rare Cause of Hemolytic Uremic Syndrome

“…Complement proteins have various roles in regulating the immune system, waste disposal, angiogenesis, regenerative processes, and lipid metabolism [1]. The pathogenesis associated with aHUS results from complement dysfunction through impairment of complement regulatory proteins and/or accelerated activation of the complement pathway [3]. Complement may be activated through the classical, lectin, and alternative pathways.…”

“…Genetic mutations in complement proteins and their regulatory proteins are found in 40-60% of patients with aHUS [1,3]. The most common mutation affects complement factor H [3].…”

“…Genetic mutations in complement proteins and their regulatory proteins are found in 40-60% of patients with aHUS [1,3]. The most common mutation affects complement factor H [3]. However, loss of function mutations in regulatory proteins and inactivating mutations in autoantibodies have all been associated with the pathogenesis of this disease.…”

“…COVID-19 has been a proposed precipitator of aHUS through effects on endothelial function and direct activation of the alternative complement pathway [2,4,5]. COVID-19 viral RNA, nucleocapsid, and spike protein have been found to accumulate in renal tubules [2,3]. COVID-19 spike protein activates the alternative complement pathway by competing with complement factor H [2][3][4]6].…”

“…COVID-19 viral RNA, nucleocapsid, and spike protein have been found to accumulate in renal tubules [2,3]. COVID-19 spike protein activates the alternative complement pathway by competing with complement factor H [2][3][4]6]. Complement cascade proteins also accumulate in the microvasculature of patients with COVID-19 [3,7,8].…”