Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature.

Introduction: As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality. Case report: We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19. His condition quickly deteriorated and he developed oliguria, accompanied with diarrhea, vomiting and oral intake intolerance. HUS was suspected, supported with compelling laboratory findings, including decreased platelets count and C3 levels, elevated LDH, urea, serum creatinine and sC5b-9 and presence of schistocytes in peripheral blood, negative fecal Shiga toxin and normal ADAMTS13 metalloprotease activity. The patient was given C5 complement blocker Ravulizumab and started to display rapid improvement. Conclusion: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.

Diagnosis and treatment of thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia, microangiopathic haemolytic anaemia and end organ damage. TMAs have varying underlying pathophysiology and can therefore present with an array of clinical presentations. Renal involvement is common as the kidney is particularly susceptible to the endothelial damage and microvascular occlusion. TMAs require rapid assessment, diagnosis, and commencement of appropriate treatment due to the high morbidity and mortality associated with them. Ground-breaking research into the pathogenesis of TMAs over the past 20 years has driven the successful development of targeted therapeutics revolutionizing patient outcomes. This review outlines the clinical presentations, pathogenesis, diagnostic tests and treatments for TMAs.

COVID-19: A Rare Cause of Hemolytic Uremic Syndrome.

Hemolytic uremic syndrome (HUS) is a multisystemic condition characterized by a triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. HUS can be classified as atypical or typical, depending upon its association with the Shiga toxin-producing Escherichia coli (STEC). Approximately 90-95% of cases are classified as typical, while only 5-10% of cases are atypical. The pathogenesis of atypical HUS (aHUS) occurs when the complement cascade is activated and causes membrane attack complex (MAC) deposition in the renal tubular epithelium. Various infectious triggers have been associated with aHUS. A new and compelling correlation to this rare and potentially deadly diagnosis of aHUS is COVID-19 infection or vaccination. We present a case of COVID-19-induced exacerbation of a patient with a known history of aHUS. In addition, we performed a literature review of previously reported COVID-19-induced aHUS cases and identified the potential pathogenesis of the disease state.

Atypical HUS Triggered by COVID-19: A Case Report.

We hereby present a case of an atypical hemolytic uremic syndrome (aHUS) precipitated by coronavirus disease 2019 (COVID-19). A 26-year-old male was diagnosed with COVID-19 and acute kidney injury. His kidney biopsy was suggestive of thrombotic microangiopathy. Five sessions of plasmapheresis were done but were discontinued in view of nonrecovery of kidney function. He was then referred for a kidney transplant. On genetic analysis, he was found to have mutations in the complement system (CFHR1 and CFHR3), which suggested this was a case of aHUS precipitated by COVID-19. In view of the high risk of recurrence of the primary disease in live-related kidney donor transplantation, he was advised for simultaneous liver and kidney transplants.

Pathology findings in pediatric patients with COVID-19 and kidney dysfunction.

BACKGROUND: Acute kidney injury (AKI) is seen in one-fifth of pediatric patients with COVID-19 requiring hospital admission, and is associated with increased morbidity, mortality, and residual kidney impairment. The majority of kidney pathology data in patients with COVID-19 is derived from adult case series and there is an overall lack of histologic data for most pediatric patients with COVID-19. METHODS: We assembled a multi-institutional cohort of five unvaccinated pediatric patients with COVID-19 and associated kidney dysfunction with available histology. RESULTS: Three complex patients with current or prior SARS-CoV-2 infection had multifactorial thrombotic microangiopathy with clinical features of hemolytic uremic syndrome (in two) or disseminated intravascular coagulation (in one); one died and another developed chronic kidney disease stage 5. Two with recently preceding SARS-CoV-2 infection presented with nephrotic syndrome; one had IgA vasculitis and one had minimal change disease. Within a short follow-up time, none has returned to baseline kidney function. CONCLUSION: Although uncommon, COVID-19-associated kidney injury can have significant morbidity in the unvaccinated pediatric and adolescent population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Relapse of Immune Thrombotic Thrombocytopenic Purpura Following Vaccination with COVID19 mRNA Vaccine.

An 84 year old male with a previous history of immune thrombotic thrombocytopenic purpura (iTTP) received the first dose of COVID19 mRNA vaccine (Pfizer-Biontech). Seven days later he was diagnosed with iTTP relapse. He received in-patient treatment with therapeutic plasma exchange, high dose steroids and rituximab and subsequently recovered. This case report highlights the need to monitor patients with iTTP following vaccination.