key: cord-0715544-hqgknfv6
authors: Kronbichler, Andreas; Jung, Se Yong; Kim, Min Seo; Shin, Jae Il
title: Distinct glomerular disease association after vaccination with BNT162b2 and mRNA-1273: A Vigibase analysis
date: 2021-11-22
journal: Kidney Int
DOI: 10.1016/j.kint.2021.11.013
sha: 719967074e4acd928edc6796972b0cc177c05e43
doc_id: 715544
cord_uid: hqgknfv6

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With the worldwide rollout of coronavirus disease 2019 (COVID-19) vaccines, numerous reports of de novo or relapsing glomerular diseases have been published recently (1) (2) (3) (4) . It has been stressed that associations between vaccination efforts and onset of disease do not prove causation, but administration of vaccines and induction of an immune response might trigger disease activity. Of note, most cases appear to be either IgA nephropathy (IgAN) or minimal change disease (MCD) (1), with around 30 cases each reported to date. Occurrence of glomerular diseases have been reported for all vaccine platforms following vaccination.

We conducted a pharmacovigilance study using the World Health Organization (WHO) global database of individual case safety reports (ICSRs) VigiBase to identify potential associations of glomerular diseases with the use of COVID-19 vaccines. 143 cases with nephrotic syndrome were reported, of whom 103 (72%) received BNT162b2 (OR 1.65, 95% CI 1.33-2.05). The risk to develop "minimal lesion GN" (as per coding) was strongly associated with the use of BNT162b2 (78.3%; OR 2.13, 95% CI 1.46-3.09). In contrast, IgAN was predominantly reported in individuals receiving mRNA-1273 (48.7%; OR 3.33, 95% CI 2.05-5.40). The risk for other glomerular diseases based on reports submitted to VigiBase was not increased (see Table 1 ). VigiBase did not indicate if patients had an established diagnosis, thus it is not possible to dissect the reported cases into de novo and relapsing glomerulonephritis.

Until August 18 th 2021, 1.8 billion people were fully vaccinated against COVID-19 and only 295 glomerulonephritis (de novo or relapsing) cases were reported to VigiBase, highlighting the relative safety of COVID-19 vaccines. Based on the high mortality rates of patients with underlying glomerular diseases (5), the benefits of COVID-19 vaccination outweigh risks. The higher rates of glomerular disease occurrence following mRNA vaccines may underline their higher immunogenicity, but we advise to use the available vaccines and platforms and comply with national vaccination recommendation with respect to 3 rd vaccine or booster doses. Some of these reported cases so far tend to have a mild and self-limiting disease course, especially patients with IgAN and MCD (1). Unfortunately, VigiBase did not provide follow-up data on the respective disease course.

In conclusion, our analysis revealed that both approved mRNA vaccines, BNT162b2 and mRNA-1273, have a different spectrum of association with glomerular diseases. The former associates with nephrotic syndrome, while the latter increases the risk to develop de novo or relapsing IgAN. Table 1 . Performance of a disproportionality analysis in Vigibase, summarizing the reports on de novo or relapsing glomerulonephritis following COVID-19 vaccination with either viral-vectored or mRNA vaccines.

Values are numbers unless otherwise indicated. Information component (IC) and its 95% credibility interval lower endpoint (IC025). A positive IC025 value (>0) is the traditional threshold used for statistical signal detection (in bold). For significant signals, reporting odds ratio (ROR) and its 95% confidence interval (95% CI were also calculated using entire database from Jan 1, 2020 to Aug 18, 2021 as comparator. Abbreviations: ADR, adverse drug reaction; AZ, AstraZeneca; FSGS, focal segmental glomerulosclerosis; GBM, glomerular basement membrane; GN: glomerulonephritis; ICSR, individual case safety report; JNJ, Johnson & Johnson; MGN, membranous glomerulonephritis; MPGN, membranoproliferative GN, NA, not applicable; RPGN, rapid-progressive glomerulonephritis; UoO, University of Oxford. *OR of BNT162b2 (Tozinameran) related nephrotic syndrome is 1.65 (95% CI, 1.33-2.05); * 1 OR of BNT162b2 (Tozinameran) related minimal GN is 2.13 (95% CI, 1.46-3.09); * 2 OR of mRNA-1273 (Elasomeran) related IgA nephropathy is 3 

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