The original version of this Article contained an error in the spelling of the author Emilien Etienne, which was incorrectly given as Emilien Ettiene. These errors have now been corrected in both the PDF and HTML versions of the Article.

Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi.

KEY POINTS: IgAN and MCD are the most common de novo glomerular diseases reported after COVID-19 vaccination, particularly after mRNA vaccination. Membranous nephropathy, pauci-immune GN, and collapsing GN have also been attributed to COVID-19 vaccination, some with dual histologies. Recovery of kidney function and proteinuria remission is more likely in IgAN and MCD by 4–6 months compared with the other glomerular diseases. BACKGROUND: Patients with de novo glomerular disease (GD) with various renal histologies have been reported after vaccination against SARS-CoV-2. Causality has not been established, and the long-term outcomes are not known. To better characterize the GDs and clinical courses/outcomes, we created the International Registry of COVID-19 vaccination and Glomerulonephritis to study in aggregate patients with de novo GN suspected after COVID-19 vaccine exposure. METHODS: A REDCap survey was used for anonymized data collection. Detailed information on vaccination type and timing and GD histology were recorded in the registry. We collected serial information on laboratory values (before and after vaccination and during follow-up), treatments, and kidney-related outcomes. RESULTS: Ninety-eight patients with GD were entered into the registry over 11 months from 44 centers throughout the world. Median follow-up was 89 days after diagnosis. IgA nephropathy (IgAN) and minimal change disease (MCD) were the most common kidney diseases reported. Recovery of kidney function and remission of proteinuria were more likely in IgAN and MCD at 4–6 months than with pauci-immune GN/vasculitis and membranous nephropathy. CONCLUSIONS: The development of GD after vaccination against SARS-CoV-2 may be a very rare adverse event. Temporal association is present for IgAN and MCD, but causality is not firmly established. Kidney outcomes for IgAN and MCD are favorable. No changes in vaccination risk-benefit assessment are recommended based on these findings.