To the editor:
Several of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines use a nucleoside-modified, purified mRNA lipid nanoparticle-encapsulated platform. Compared with traditional inactivated viral and adjuvanted protein vaccines, this RNA platform elicits far higher neutralizing antibody titers, stronger antigen-specific cluster of differentiation (CD) 4+ and CD8+ T-cell responses, and stronger germinal center B and TFH cell activation in experimental animals.1 The activated CD4+ and CD8+ T cells produce several proinflammatory cytokines, including interferon-γ and tumor necrosis factor-α. This led us to wonder if these vaccines may activate or exacerbate immune-mediated glomerular diseases. Two individuals with biopsy-proven IgA nephropathy (IgAN) developed gross hematuria shortly following the second dose of the Moderna vaccine. The patients are described in Table 1 . At baseline, both had proteinuria of <1 g/d and well-preserved kidney function. Several hours after the second dose of vaccine was given, both developed systemic symptoms, ranging from body aches, headache, and fatigue to fever and chills. Between 8 and 24 hours after systemic symptoms appeared, the patients noticed gross hematuria that resolved after 3 days. Serum creatinine did not increase, but proteinuria increased in 1 patient (Table 1). Although we did not expect an exacerbation of IgAN after a nonmucosal immune challenge, IgAN patients have previously been reported to have a stronger IgA1 (albeit monomeric) response to intramuscular influenza vaccine than healthy subjects.2 These episodes of apparent IgAN exacerbation should prompt the nephrology community to closely follow their patients with glomerular disease after SAR2-CoV-2 vaccination to determine the frequency and consequences of vaccine-induced disease activation.
Table 1.
Patient demographics and clinical characteristics
| Patient no. | Age, yr | Sex | Race | Year IgAN diagnosed | Treatment | Gross hematuria events during disease course | Persistent microscopic hematuria |
Proteinuria in 2020, g/d | Proteinuria between SARS-Cov-2 vaccine doses, g/d | Proteinuria 3 weeks after last SARS-CoV-2 vaccine dose, g/d |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 38 | F | W | 2005 | RAASi | At presentation; during 1 episode of gastroenteritis; occasionally after yearly influenza vaccine |
Yes | 0.63 | 0.82 | 1.40 |
| 2 | 38 | F | W | 2019 | Cyc + Pred (6 mo), then RAASi | At presentation only | Yes | 0.43 | 0.59 | 0.40 |
Cyc, cyclophosphamide; F, female; IgAN, IgA nephropathy; Pred, prednisone; RAASi, renin-angiotensin-aldosterone system inhibitor; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; W, white.
Footnotes
see commentary on page 1275
References
- 1.Pardi N., Hogan M.J., Naradikian M.S. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018;215:1571–1588. doi: 10.1084/jem.20171450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.van den Wall Bake A.W., Beyer W.E., Evers-Schouten J.H. Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy: an analysis of isotype distribution and size of the influenza-specific antibodies. J Clin Invest. 1989;84:1070–1075. doi: 10.1172/JCI114269. [DOI] [PMC free article] [PubMed] [Google Scholar]