Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 1:13:1056153.
doi: 10.3389/fimmu.2022.1056153. eCollection 2022.

COVID-19 vaccination and Atypical hemolytic uremic syndrome

Romy N Bouwmeester  1 , Esther M G Bormans  1 , Caroline Duineveld  2 , Arjan D van Zuilen  3 , Anne-Els van de Logt  2 , Jack F M Wetzels  2 , Nicole C A J van de Kar  1
Affiliations

COVID-19 vaccination and Atypical hemolytic uremic syndrome

Romy N Bouwmeester et al. Front Immunol. .

Abstract

Introduction: COVID-19 vaccination has been associated with rare but severe complications characterized by thrombosis and thrombocytopenia.

Methods and results: Here we present three patients who developed de novo or relapse atypical hemolytic uremic syndrome (aHUS) in native kidneys, a median of 3 days (range 2-15) after mRNA-based (Pfizer/BioNTech's, BNT162b2) or adenoviral (AstraZeneca, ChAdOx1 nCoV-19) COVID-19 vaccination. All three patients presented with evident hematological signs of TMA and AKI, and other aHUS triggering or explanatory events were absent. After eculizumab treatment, kidney function fully recovered in 2/3 patients. In addition, we describe two patients with dubious aHUS relapse after COVID-19 vaccination. To assess the risks of vaccination, we retrospectively evaluated 29 aHUS patients (n=8 with native kidneys) without complement-inhibitory treatment, who received a total of 73 COVID-19 vaccinations. None developed aHUS relapse after vaccination.

Conclusion: In conclusion, aHUS should be included in the differential diagnosis of patients with vaccine-induced thrombocytopenia, especially if co-occuring with mechanical hemolytic anemia (MAHA) and acute kidney injury (AKI). Still, the overall risk is limited and we clearly advise continuation of COVID-19 vaccination in patients with a previous episode of aHUS, yet conditional upon clear patient instruction on how to recognize symptoms of recurrence. At last, we suggest monitoring serum creatinine (sCr), proteinuria, MAHA parameters, and blood pressure days after vaccination.

Keywords: COVID-19; SARS-CoV-2; aHUS; atypical hemolitic uremic syndrome; complement; thrombotic microagiopathy; trigger; vaccination.

PubMed Disclaimer

Conflict of interest statement

JW is a member of the international advisory board of Alexion and also received a grant from Alexion. NvdK has received a consultancy fee from Roche Pharmaceuticals and Novartis and is a sub-investigator in the APL2-C3G trial, Apellis. AB received a consultancy fee from Novartis, is a member of the DSMB Zoster-047 trial, GSK, and a sub-investigator in the Belatacept study, BMS. VG is sub-investigator in the APL2-C3G trial, Apellis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of serum creatinine, proteinuria, and TMA parameters over time in all patients. Overview trend of serum creatinine, proteinuria and TMA parameters LDH and thrombocytes (platelet count). [1] Only one measurement of UPCR was available in patient one. Before the second COVID-19 vaccination, a prophylactic dose of eculizumab was given.
See this image and copyright information in PMC

References

    1. Westra D, Wetzels JF, Volokhina EB, van den Heuvel LP, van de Kar NC. A new era in the diagnosis and treatment of atypical haemolytic uraemic syndrome. Neth J Med (2012) 70(3):121–9. - PubMed
    1. Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C. Haemolytic uraemic syndrome. Lancet (2017) 390(10095):681–96. doi: 10.1016/S0140-6736(17)30062-4 - DOI - PubMed
    1. Fakhouri F, Fila M, Hummel A, Ribes D, Sellier-Leclerc AL, Ville S, et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: A prospective multicenter study. Blood (2021) 137(18):2438–49. doi: 10.1182/blood.2020009280 - DOI - PubMed
    1. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med (2014) 371(7):654–66. doi: 10.1056/NEJMra1312353 - DOI - PubMed
    1. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis (2011) 6:60. doi: 10.1186/1750-1172-6-60 - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data