Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic review

BackgroundSince its first reported case in December 2019, COVID-19 disease, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), evolved into a major pandemic throughout the world. Although COVID-19 is most often characterized as a respiratory pathology, there are also extensive reports of...

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Main Authors: Brendan M. Coyne, Danielle Ito, Anam Tariq, Susie Q. Lew, Jeffrey Kopp, Patricia Centron Vinales, Fahim Malik, Patrick E. Gipson, Ehsan Nobakht
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1568943/full
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author Brendan M. Coyne
Danielle Ito
Anam Tariq
Susie Q. Lew
Jeffrey Kopp
Patricia Centron Vinales
Fahim Malik
Patrick E. Gipson
Ehsan Nobakht
author_facet Brendan M. Coyne
Danielle Ito
Anam Tariq
Susie Q. Lew
Jeffrey Kopp
Patricia Centron Vinales
Fahim Malik
Patrick E. Gipson
Ehsan Nobakht
author_sort Brendan M. Coyne
collection DOAJ
description BackgroundSince its first reported case in December 2019, COVID-19 disease, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), evolved into a major pandemic throughout the world. Although COVID-19 is most often characterized as a respiratory pathology, there are also extensive reports of renal complications, such as glomerulonephritis (GN). However, the precise nature of COVID-associated glomerulonephritis (COVID-GN) has yet to be fully understood. This review seeks to elucidate COVID-GN pathophysiology by conducting an exhaustive systematic review.MethodsHerein, we compare the different GN subtypes associated with COVID-19 in the literature. We also review the cytokines, antibodies, and genes most implicated in COVID-GN.ResultsThe GN subtype with the highest number of cases associated with COVID-19 infection was focal segmental glomerulosclerosis, specifically the collapsing morphology. Meanwhile, the highest number of cases associated with COVID-19 vaccination was IgA nephropathy. The most prevalent mechanism in the literature for COVID-GN involves a cytokine storm, which may be accompanied by immune complex deposition.DiscussionBoth infection and vaccination from SARS-CoV-2 can induce robust CD4+ T cell responses promoted by an IL-6 amplifier loop of inflammation. This immune response is likely further enhanced by interactions with complement systems and the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2-mediated pathways of both direct cytotoxicity and stimulation of polyclonal immunoglobulin may converge to cause glomerular inflammation and injury. Further investigation of these inflammatory pathways may provide insight into COVID-19 pathophysiology, treatment, and long-term outcomes.
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spelling doaj-art-b0d05eeedf9348bba6eca494b70378572025-08-20T03:09:51ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.15689431568943Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic reviewBrendan M. Coyne0Danielle Ito1Anam Tariq2Susie Q. Lew3Jeffrey Kopp4Patricia Centron Vinales5Fahim Malik6Patrick E. Gipson7Ehsan Nobakht8George Washington School of Medicine and Health Sciences, Washington, DC, United StatesDepartment of Biological Sciences, University of California, Irvine, Irvine, CA, United StatesGeorge Washington School of Medicine and Health Sciences, Washington, DC, United StatesGeorge Washington School of Medicine and Health Sciences, Washington, DC, United StatesNational Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD, United StatesGeorge Washington School of Medicine and Health Sciences, Washington, DC, United StatesWashington Nephrology Associates, Rockville, MD, United StatesGeorge Washington School of Medicine and Health Sciences, Washington, DC, United StatesGeorge Washington School of Medicine and Health Sciences, Washington, DC, United StatesBackgroundSince its first reported case in December 2019, COVID-19 disease, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), evolved into a major pandemic throughout the world. Although COVID-19 is most often characterized as a respiratory pathology, there are also extensive reports of renal complications, such as glomerulonephritis (GN). However, the precise nature of COVID-associated glomerulonephritis (COVID-GN) has yet to be fully understood. This review seeks to elucidate COVID-GN pathophysiology by conducting an exhaustive systematic review.MethodsHerein, we compare the different GN subtypes associated with COVID-19 in the literature. We also review the cytokines, antibodies, and genes most implicated in COVID-GN.ResultsThe GN subtype with the highest number of cases associated with COVID-19 infection was focal segmental glomerulosclerosis, specifically the collapsing morphology. Meanwhile, the highest number of cases associated with COVID-19 vaccination was IgA nephropathy. The most prevalent mechanism in the literature for COVID-GN involves a cytokine storm, which may be accompanied by immune complex deposition.DiscussionBoth infection and vaccination from SARS-CoV-2 can induce robust CD4+ T cell responses promoted by an IL-6 amplifier loop of inflammation. This immune response is likely further enhanced by interactions with complement systems and the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2-mediated pathways of both direct cytotoxicity and stimulation of polyclonal immunoglobulin may converge to cause glomerular inflammation and injury. Further investigation of these inflammatory pathways may provide insight into COVID-19 pathophysiology, treatment, and long-term outcomes.https://www.frontiersin.org/articles/10.3389/fmed.2025.1568943/fullCOVID-19glomerulonephritisglomerulopathiesCOVID-19 associated nephropathyimmunologyimmune complex
spellingShingle Brendan M. Coyne
Danielle Ito
Anam Tariq
Susie Q. Lew
Jeffrey Kopp
Patricia Centron Vinales
Fahim Malik
Patrick E. Gipson
Ehsan Nobakht
Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic review
Frontiers in Medicine
COVID-19
glomerulonephritis
glomerulopathies
COVID-19 associated nephropathy
immunology
immune complex
title Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic review
title_full Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic review
title_fullStr Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic review
title_full_unstemmed Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic review
title_short Ascertaining the mechanistic etiology of COVID-associated glomerulonephritis: a systematic review
title_sort ascertaining the mechanistic etiology of covid associated glomerulonephritis a systematic review
topic COVID-19
glomerulonephritis
glomerulopathies
COVID-19 associated nephropathy
immunology
immune complex
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1568943/full
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