Autor:innen:
C. Van Quekelberghe (Frankfurt, DE)
M. Hansen (Frankfurt , DE)
G. Visciani (Frankfurt , DE)
S. Kunzmann (Frankfurt , DE)
K. Latta (Frankfurt , DE)
We present 2 cases of infants admitted with febrile COVID19 infection and developing atypical haemolytic uremic syndrome (aHUS) during the first week of hospitalization.
AHUS is a rare disease due to uncontrolled activation of the complement system and characterized by systemic thrombotic microangiopathy (TMA), mainly in the kidneys, leading to acute renal failure.
There is increasing evidence that COVID-19 is associated with microvascular injury. Furthermore complement activation plays a role in the pathogenesis of severe COVID-19-disiease.
First case
A 4-month-old boy, ex-premature of 26 weeks, was admitted with a febrile COVID-19 infection. On day 5 typical signs of HUS developed (anaemia, thrombocytopenia, high LDH and progressive kidney failure) and the boy was admitted to the PICU on day 8 for Tenckhoff-catheter implantation, peritoneal dialysis and management of Hypertension.
Due to high suspicion of aHUS, eculizumab was given on day 8. With this treatment he improved constantly and peritoneal dialysis could be stopped after 4 weeks.
Thrombotic thrombocytopenic Purpura (TTP) was excluded by normal ADAMTS-13 values.
The boy was discharged after 6 weeks with remaining serious arterial hypertension.
Second Case
A 4,5-month-old boy was admitted with fever, diarrhea and reduced drinking for 3 days.
SARS-CoV-2 PCR testing was positive, initial blood cell count, infection signs, lumbar punction and chest x-ray were unremarkable, blood gas showed mild dehydration. Kidney ultrasound was normal on admission. Initially he received fluid resuscitation and antipyretic treatment.
On day 4, he developed anaemia, thrombocytopenia, rising LDH, schistocytes and echogenic kidneys. Given the clinical suspicion of atypical HUS we immediately treated with Eculizumab. Despite this treatment the child developed acute kidney failure with anuria, severe arterial hypertension, requiring PICU admission and peritoneal dialysis on day 8. Initially arterial hypertension was refractory to triple IV-continuous treatment. However, during dialysis de-escalation was slowly possible.
As for case 1, TTP was ruled out by normal ADAMTS-13 values. Stool screening was unremarkable. Further Complement functional studies and genetic screening are ongoing.
Discussion:
It is well known that aHUS can be triggered by infectious disease, so that in our two cases the Covid-19-infection might just have served as a trigger, but in general aHUS is a rare disease, so two similar cases within a month is very unexpected. There is growing evidence that severe Covid 19 disease is linked to disproportionate complement activation leading to thrombotic complications and poor outcome. Therefore, the development of a complement-mediated thrombotic microangiopathy in our two cases might be the result of a severe Covid-19 infection with overactivated complement system directly due to the Covid virus and not necessarily due to an underlying genetic complement disorder.