De novo vasculitis after mRNA-1273 (Moderna) vaccination

To the editor:

The mRNA-1273 (Moderna) vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the current coronavirus disease 2019 (COVID-19) pandemic. In a randomized placebo-controlled phase 3 trial, the mRNA-1273 (Moderna) vaccine showed high efficacy at preventing COVID-19. Aside from transient local and systemic reactions, no safety concerns were identified.¹

Here we report 2 patients who developed de novo vasculitis shortly after receiving the mRNA-1273 (Moderna) vaccine.

Patient 1 was a 39-year-old man with a history of treated arterial hypertension. After a well-tolerated first dose of mRNA-1273 (Moderna) vaccine, he had severe fever, flu-like symptoms, and macrohematuria immediately after the second dose. Diagnostic workup showed acute kidney injury (AKI) with nephritic syndrome. Repeat reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from nasopharyngeal swabs was negative. A kidney biopsy revealed severe crescentic IgA nephritis (Figure 1 a–d). Treatment with high-dose glucocorticoids and cyclophosphamide was initiated. Over the following weeks, serum creatinine normalized and proteinuria significantly decreased, but microhematuria persisted.

Figure 1.

(a–d) Histopathologic findings of patient 1 with (a,b) crescentic IgA nephritis and (c,d) mesangial IgA deposition on immunofluorescence and electron microscopy, and histopathologic findings of patient 2 with (e,f) severe necrotizing vasculitis, but (g,h) without deposition of Igs on immunofluorescence and electron microscopy. (a) Hematoxylin-eosin and silver staining (original magnification ×20). (b) Acid fuchsin–orange G stain (original magnification ×20). (c) Immunofluorescence against IgA (original magnification ×20). (d) Transmission electron microscopy. The arrowhead shows mesangial IgA depot. (e) Periodic acid–Schiff stain (original magnification ×20). (f) Acid fuchsin–orange G stain (original magnification ×20). (g) Immunofluorescence against IgA (original magnification ×20). (h) Transmission electron microscopy. Bar = 100 μm for light microscopy and immunofluorescence, and bar = 1 μm for electron microscopy. To optimize viewing of this image, please see the online version of this article at www.kidney-international.org.

Patient 2 was a healthy 81-year-old man. After the first dose of the mRNA-1273 (Moderna) vaccine, he had sustained flu-like symptoms, which significantly worsened after the second dose. Laboratory workup showed AKI, proteinuria in the nonnephrotic range, and an elevated proteinase 3 (PR3) anti–neutrophil cytoplasmic antibody (ANCA) titer. A pulmonary computed tomography scan demonstrated bilateral necrotic masses of the lung parenchyma and slight pleural effusion, without evidence of tumor or lymphadenopathy. Repeat RT-PCR testing for SARS-CoV-2 from nasopharyngeal swabs was negative; serologic testing for SARS-CoV-2 showed a positive anti-spike IgG and negative anti-nucleocapsid IgG. A kidney biopsy performed at day 22 after the second vaccine dose showed severe pauci-immune crescentic glomerulonephritis with capillary necrosis and vasculitis present in the renal vessel walls (Figure 1e–h). The patient was treated with high-dose glucocorticoids, cyclophosphamide, and plasmapheresis. Over the course of 3 weeks, the patient’s symptoms disappeared, and renal function improved along with a significant decrease of PR3-ANCA and anti-spike IgG titer. Immunohistochemical staining for the SARS-CoV-2 spike protein was negative in both patients.

Appearance of AKI concurrently with serious systemic symptoms shortly after the second dose strongly suggests a causal mechanism. Isolated cases of SARS-CoV-2–induced IgA vasculitis and ANCA-associated vasculitis have been reported.^{2 , 3} In contrast, 2 patients with preexisting IgA nephropathy have been reported to experience gross hematuria after receiving the mRNA-1273 (Moderna) vaccine, with spontaneous resolution after 3 days.⁴ Two cases of minimal change nephropathy associated with the BNT162b2 mRNA (Pfizer-BioNTech) vaccine have also been described.^{5 , 6}

To our knowledge, these are the first 2 cases of de novo vasculitis after vaccination with an mRNA-based vaccine.

The mechanism remains to be elucidated but is likely due to aberrant immune response to the spike protein or mRNA of SARS-CoV-2 in predisposed individuals.

We hope that this correspondence will prompt clinicians to consider vasculitis workup in the case of protracted systemic reactions, new-onset macrohematuria, or worsening kidney function after vaccination with mRNA-based SARS-CoV-2 vaccines. Given the massive scale-up of vaccination efforts worldwide, it is very likely that additional cases of vaccination-induced vasculitis will emerge. We strongly encourage additional reporting and communication for this rare, albeit severe, side effect of the mRNA-1273 (Moderna) vaccine.

Disclosure

DGF reports unrestricted research grants from Otsuka and Boehringer Ingelheim and consulting fees from Otsuka and Alnylam. All the other authors declared no competing interests.