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SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids.

ABSTRACT: Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.

SUBMITTER: Jansen J

PROVIDER: S-EPMC8709832 | biostudies-literature |

REPOSITORIES: biostudies-literature

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SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Project description:Single-cell RNA-seq of iPSC derived human kidney organoids. Single-nuclei RNA-seq data of COVID-19 patient autopsy kidney tissue. The current data was used to suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury as well as a pro-fibrotic environment which could explain acute kidney injury in COVID-19 patients and also long-term effects potentially leading to the development of chronic kidney disease.

2021-12-16 | GSE167747 | GEO

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Project description:SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

| PRJNA705189 | ENA

SARS-CoV-2 productively infects human gut enterocytes

Project description: Not available

| EMPIAR-10404 | biostudies-other

SARS-CoV-2 infects human neural progenitor cells and brain organoids.

Project description: Not available

| S-EPMC7399356 | biostudies-literature

SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids.

Project description:Several studies have pointed to retinal involvement in COVID-19, yet many questions remain regarding the ability of SARS-CoV-2 to infect and replicate in retinal cells and its effects on the retina. Here, we have used human pluripotent stem cell-derived retinal organoids to study retinal infection by SARS-CoV-2. Indeed, SARS-CoV-2 can infect and replicate in retinal organoids, as it is shown to infect different retinal lineages, such as retinal ganglion cells and photoreceptors. SARS-CoV-2 infection of retinal organoids also induces the expression of several inflammatory genes, such as interleukin 33, a gene associated with acute COVID-19 and retinal degeneration. Finally, we show that the use of antibodies to block ACE2 significantly reduces SARS-CoV-2 infection of retinal organoids, indicating that SARS-CoV-2 infects retinal cells in an ACE2-dependent manner. These results suggest a retinal involvement in COVID-19 and emphasize the need to monitor retinal pathologies as potential sequelae of "long COVID."

| S-EPMC8943915 | biostudies-literature

Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids.

Project description:COVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) pathway by viral infection remain poorly characterized. Using induced pluripotent stem cell-derived kidney organoids, SARS-CoV-1, SARS-CoV-2, and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2, NRP1 or DPP4) and protease (TMPRSS2, TMPRSS4, FURIN, CTSB or CTSL), was identified primarily among proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in patients with COVID-19, inhibited angiotensin II-mediated internalization of ACE2, upregulated interferon-stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.

| S-EPMC8795780 | biostudies-literature

SARS-CoV-2 Infects the Brain Choroid Plexus and Disrupts the Blood-CSF Barrier in Human Brain Organoids.

Project description:Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells but little to no infection of neurons or glia. We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells, and cytokines into cerebrospinal fluid and the brain.

| S-EPMC7553118 | biostudies-literature

SARS-CoV-2 productively infects human gut enterocytes.

Project description:The virus severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission via the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were detected. mRNA expression analysis revealed strong induction of a generic viral response program. Hence, intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology.

| S-EPMC7199907 | biostudies-literature

SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids

Project description:Recent data suggests that COVID-19 is a systemic disease affecting multiple organs including the central nervous system. Retinal involvement in COVID-19 has been indicated by several studies, yet many questions remain regarding the ability of SARS-CoV-2 to infect and replicate retinal cells and its effect on the retina. Here we have used human stem cell derived retinal organoids to study retinal infection by SARS-CoV-2. Indeed, SARS-CoV-2 can infect and replicate in retinal organoids, as it is shown to be able to infect different retinal lineages, including retinal ganglion cells and photoreceptors which are the targets of many retinal diseases leading to blindness. SARS-CoV-2 infection of retinal organoids also induces the expression of several inflammatory genes, including Interleukin 33, which is known to be associated with acute COVID-19 disease and with retinal degeneration. Finally, we show that blocking the ACE2 receptor using antibody treatment significantly reduces retinal organoid infection, indicating that SARS-CoV-2 infects retinal cells in an ACE2 dependent manner. These results suggest a direct retinal involvement in COVID-19, and emphasize the need to monitor retinal pathologies as a possible element of “long COVID”.

2022-01-01 | GSE174843 | GEO

SARS-CoV-2 productively infects human brain microvascular endothelial cells.

Project description:BackgroundThe emergence of the novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency. SARS-CoV-2 is highly contagious and has a high mortality rate in severe patients. However, there is very limited information on the effect of SARS-CoV-2 infection on the integrity of the blood-brain barrier (BBB).MethodsRNA-sequencing profiling was performed to analyze the transcriptomic changes in human brain microvascular endothelial cells (hBMECs) after SARS-CoV-2 infection. Bioinformatic tools were used for differential analysis. Immunofluorescence, real-time quantitative PCR, and Western blotting analysis were used to explore biological phenotypes.ResultsA total of 927 differentially expressed genes were identified, 610 of which were significantly upregulated while the remaining 317 were downregulated. We verified the significant induction of cytokines, chemokines, and adhesion molecules in hBMECs by SARS-CoV-2, suggesting an activation of the vascular endothelium in brain. Moreover, we demonstrated that SARS-CoV-2 infection could increase the BBB permeability, by downregulating as well as remodeling the intercellular tight junction proteins.ConclusionsOur findings demonstrated that SARS-CoV-2 infection can cause BBB dysfunction, providing novel insights into the understanding of SARS-CoV-2 neuropathogenesis. Moreover, this finding shall constitute a new approach for future prevention and treatment of SARS-CoV-2-induced CNS infection.

| S-EPMC9198209 | biostudies-literature

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