The pathogenesis of COVID-19-induced IgA nephropathy and IgA vasculitis: A systematic review

Abstract

Objective IgA nephropathy (IgAN) and IgA vasculitis (IgAV) are part of a similar clinical spectrum. Both clinical conditions occur with the coronavirus disease 2019 (COVID-19). This review aims to recognize the novel association of IgAN and IgAV with COVID-19 and describe its underlying pathogenesis. Methods We conducted a systematic literature search and data extraction from PubMed, Cochrane, ScienceDirect, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Our search identified 13 cases reporting IgAV and IgAN associated with COVID-19 infection and 4 cases of IgAN following COVID-19 vaccination. The mean, mode, and median ages of patients were 23.8, 4, and 8 years, respectively. Most cases associated with COVID-19 infection were reported in males (76.9%). Rash and purpura (84.6%) were the most common clinical features, followed by gastrointestinal symptoms (61.5%). In symptomatic cases, skin or renal biopsy and immunofluorescence confirmed the diagnosis of IgAN or IgAV. Most patients were treated with steroids and reported recovery or improvement; however, death was reported in two patients. Conclusion There is a paucity of scientific evidence on the pathogenesis of the association of IgAN and IgAV vasculitis with COVID-19, which thus needs further study. Current research suggests the role of IgA-mediated immune response, evidenced by early seroconversion to IgA in COVID-19 patients and the role of IgA in immune hyperactivation as the predominant mediator of the disease process. Clinicians, especially nephrologists and paediatricians, need to recognize this association, as this disease is usually self-limited and can lead to complete recovery if prompt diagnosis and treatment are provided.

Elevated levels of IL-6 in IgA nephropathy patients are induced by an epigenetically driven mechanism modulated by viral and bacterial RNA

“…Also, recent data showing 13 IgAN cases associated with COVID-19 infection and 4 cases of IgAN following COVID-19 RNA-vaccination(44) may be clearly explained by our discovered mechanism trough the PKR activation by RNA (Figure 7).…”

COVID-19 and kidney disease: insights from epidemiology to inform clinical practice

“…A number of case reports suggest that COVID-19 may induce de novo immune-mediated kidney diseases such as IgA nephropathy 92 , vasculitis 93 , membranous nephropathy 94 , minimal change disease 95 and collapsing focal segmental glomerulosclerosis 96 , 97 . Larger studies are needed to quantify the extent of these associations by comparing, for example, the incidence of specific kidney diseases before and after the pandemic within histopathology registries 98 .…”

Development of IgA vasculitis with severe glomerulonephritis after COVID-19 vaccination: a case report and literature review

“…With the spread of the COVID-19 pandemic and the COVID-19 vaccine programs worldwide, new-onset and relapses of primary kidney disease/vasculitis with kidney involvement that developed after COVID-19 vaccination have recently been reported [7][8][9][10][11][12]. The association between hematuria following a COVID-19 vaccination with the onset or relapse of IgA nephropathy [13] has been attracting attention, and reports of IgAV (Henoch-Schönlein purpura with/without kidney complication) after COVID-19 vaccination are also increasing in number [14][15][16][17][18][19][20][21][22].…”