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Coronavirus Disease 2019-Associated Thrombotic Microangiopathy: Literature Review
Marija Malgaj Vrečko1,2, Andreja Aleš Rigler1,2, Željka Večerić-Haler1,2
1Department of Nephrology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia.
Insights
COVID-19 can cause kidney injury, specifically thrombotic microangiopathy (TMA). This review found TMA, including thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS), occurred in patients with COVID-19, sometimes without severe respiratory symptoms.
Area of Science:
- Nephrology
- Hematology
- Infectious Diseases
Background:
- COVID-19 is associated with multisystem disorders, including significant kidney involvement.
- Thrombotic microangiopathy (TMA) is a frequent renal complication of COVID-19, presenting as either TTP or aHUS.
- Genetic predisposition may play a role in the development of COVID-19-associated TMA.
Purpose of the Study:
- To review and analyze global literature on cases of TMA associated with COVID-19.
- To describe the clinical presentation, treatment, and outcomes of COVID-19-associated TMA.
- To explore the potential role of COVID-19 as a trigger for TMA in susceptible individuals.
Main Methods:
- Systematic review of global literature for cases of TMA in COVID-19 patients.
- Analysis of patient demographics, clinical presentations, laboratory findings, treatments, and outcomes.
- Categorization of TMA cases into TTP and aHUS subtypes.
Main Results:
- 46 cases of COVID-19-associated TMA were identified, with 18 TTP and 28 aHUS.
- Seven aHUS patients had known genetic complement abnormalities.
- Treatments included plasma exchange, corticosteroids, rituximab, and C5 inhibitors, with mortality rates of 16.7% for TTP and 10.7% for aHUS.
Conclusions:
- COVID-19-associated TMA, including TTP and aHUS, can occur with varying COVID-19 symptom severity.
- COVID-19 may act as a second hit in genetically predisposed individuals, triggering TMA.
- Early diagnosis and tailored treatment are crucial for improving outcomes in COVID-19-associated TMA.
Abstract:
Coronavirus disease 2019 (COVID-19) can lead to clinically significant multisystem disorders that also affect the kidney. According to recent data, renal injury in the form of thrombotic microangiopathy (TMA) in native kidneys ranks third in frequency. Our review of global literature revealed 46 cases of TMA in association with COVID-19. Among identified cases, 18 patients presented as thrombotic thrombocytopenic purpura (TTP) and 28 cases presented as atypical hemolytic uremic syndrome (aHUS). Altogether, seven patients with aHUS had previously proven pathogenic or likely pathogenic genetic complement abnormalities. TMA occurred at the time of viremia or even after viral clearance. Infection with COVID-19 resulted in almost no or only mild respiratory symptoms in the majority of patients, while digestive symptoms occurred in almost one-third of patients. Regarding the clinical presentation of COVID-19-associated TMA, the cases showed no major deviations from the known presentation. Patients with TTP were treated with plasma exchange (88.9%) or fresh frozen plasma (11.1%), corticosteroids (88.9%), rituximab (38.9%), and caplacizumab (11.1%). Furthermore, 53.6% of patients with aHUS underwent plasma exchange with or without steroid as initial therapy, and 57.1% of patients received a C5 complement inhibitor. Mortality in the studied cohort was 16.7% for patients with TTP and 10.7% for patients with aHUS. The exact role of COVID-19 in the setting of COVID-19-associated TMA remains unclear. COVID-19 likely represents a second hit of aHUS or TTP that manifests in genetically predisposed individuals. Early identification of the TMA subtype and appropriate prompt and specific treatment could lead to good outcomes comparable to survival and recovery statistics for TMA of all causes.
